Colorectal cancer, RAS wild-type

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Note: the page has systemic regimens for the more general category of RAS wild-type colorectal cancer. Also note that most of the regimens were evaluated on patients tested for KRAS mutations only, and that the definition of wild-type has evolved over time. See individual regimen biomarker eligibility criteria for more details. 
*See the main colorectal cancer page for general regimens.
*See the RAS wild-type colon cancer page for adjuvant colon cancer regimens.
Last updated on 2024-07-23:27 regimens on this page
40 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ESMO==
*2016: van Cutsem et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. EuroPMC
*2013: Balmaña et al. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. EuroPMC
==Japanese Society for Cancer of the Colon and Rectum==
*2016: Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer link to PMC article EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Colon Cancer.
=Perioperative therapy for oligometastatic disease=
==FOLFIRI==
FOLFIRI: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ye et al. 2013 (Fudan 2012-03)	2008-2011 	Phase 3 (C)	1a. FOLFIRI & Cetuximab1b. mFOLFOX6 & Cetuximab	Shorter OSMedian OS: 21 vs 30.9 mo(HR 1.85, 95% CI 1.14-3.03)
Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
14-day cycles until lesions deemed resectable or up to 12 cycles
===References===
#Fudan 2012-03: Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. Epub 2013 Apr 8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01564810
==FOLFIRI & Cetuximab==
FOLFIRI & Cetuximab: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan, Cetuximab
===Regimen variant #1, weekly cetuximab===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ye et al. 2013 (Fudan 2012-03)	2008-2011 	Phase 3 (E-esc)	1a. FOLFIRI1b. mFOLFOX6	Longer OS (secondary endpoint)Median OS: 30.9 vs 21 mo(HR 0.54, 95% CI 0.33-0.88)Higher rate of patients converted to resection for liver metastases (primary endpoint)
Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) as follows, given first:
**Cycle 1: 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once on day 8
**Cycles 2 up to 12: 250 mg/m2 IV once per day on days 1 & 8
14-day cycles until lesions deemed resectable or up to 12 cycles
===Regimen variant #2, bi-weekly cetuximab===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ye et al. 2013 (Fudan 2012-03)	2008-2011 	Phase 3 (E-esc)	1a. FOLFIRI1b. mFOLFOX6	Longer OS (secondary endpoint)Median OS: 30.9 vs 21 mo(HR 0.54, 95% CI 0.33-0.88)
Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) 500 mg/m2 IV once on day 1, given first
14-day cycles until lesions deemed resectable or up to 12 cycles
===References===
#Fudan 2012-03: Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. Epub 2013 Apr 8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01564810
==mFOLFOX6==
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
===Regimen variant #1, 400/2800/85, resectable or suboptimally resectable===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Primrose et al. 2014 (New EPOC)	2007-2012 	Phase 3 (C)	mFOLFOX6 & Cetuximab	Did not meet primary endpoint of PFS1Median PFS: 22.2 vs 15.5 mo(HR 0.85, 95% CI 0.64-1.15)
1Reported efficacy is based on the 2020 update.
Note: this trial was only open to KRAS wild-type patients with resectable or suboptimally resectable colorectal liver metastases.
====Biomarker eligibility criteria====
*KRAS wild-type
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for 6 cycles, then surgery, then 14-day cycle for 6 cycles
===Regimen variant #2, 400/2800/85, unresectable===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ye et al. 2013 (Fudan 2012-03)	2008-2011 	Phase 3 (C)	1a. FOLFIRI & Cetuximab1b. mFOLFOX6 & Cetuximab	Shorter OSMedian OS: 21 vs 30.9 mo(HR 1.85, 95% CI 1.14-3.03)
Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycles until lesions deemed resectable or up to 12 cycles
===References===
#Fudan 2012-03: Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. Epub 2013 Apr 8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01564810
#New EPOC: Primrose J, Falk S, Finch-Jones M, Valle J, O'Reilly D, Siriwardena A, Hornbuckle J, Peterson M, Rees M, Iveson T, Hickish T, Butler R, Stanton L, Dixon E, Little L, Bowers M, Pugh S, Garden OJ, Cunningham D, Maughan T, Bridgewater J. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol. 2014 May;15(6):601-11. Epub 2014 Apr 7. Erratum in: Lancet Oncol. 2014 Jun;15(7):e253. link to original article EuroPMC ISRCTN22944367
##Update: Bridgewater JA, Pugh SA, Maishman T, Eminton Z, Mellor J, Whitehead A, Stanton L, Radford M, Corkhill A, Griffiths GO, Falk S, Valle JW, O'Reilly D, Siriwardena AK, Hornbuckle J, Rees M, Iveson TJ, Hickish T, Garden OJ, Cunningham D, Maughan TS, Primrose JN; New EPOC investigators. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2020 Mar;21(3):398-411. Epub 2020 Jan 31. link to original article link to PMC article EuroPMC
==mFOLFOX6 & Cetuximab==
mFOLFOX6 & Cetuximab: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Cetuximab
===Regimen variant #1, weekly cetuximab===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ye et al. 2013 (Fudan 2012-03)	2008-2011 	Phase 3 (E-esc)	1a. FOLFIRI1b. mFOLFOX6	Longer OS (secondary endpoint)Median OS: 30.9 vs 21 mo(HR 0.54, 95% CI 0.33-0.88)
Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) as follows, given first:
**Cycle 1: 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once on day 8
**Cycles 2 up to 12: 250 mg/m2 IV once per day on days 1 & 8
14-day cycles until lesions deemed resectable or up to 12 cycles
===Regimen variant #2, bi-weekly cetuximab===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ye et al. 2013 (Fudan 2012-03)	2008-2011 	Phase 3 (E-esc)	1a. FOLFIRI1b. mFOLFOX6	Longer OS (secondary endpoint)Median OS: 30.9 vs 21 mo(HR 0.54, 95% CI 0.33-0.88)
Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) 500 mg/m2 IV once on day 1, given first
14-day cycles until lesions deemed resectable or up to 12 cycles
===References===
#Fudan 2012-03: Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. Epub 2013 Apr 8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01564810
=Advanced or metastatic disease, first-line=
==CapeOx & Panitumumab==
CapeOx & Panitumumab: Capecitabine, Oxaliplatin, Panitumumab
===Regimen===
Study 	Dates of enrollment 	Evidence
Papaxoinis et al. 2018 (HE 6A/09)	2010-10-13 to 2013-09-10	Phase 2
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
*Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
====Targeted therapy====
*Panitumumab (Vectibix) 9 mg/kg IV once on day 1
21-day cycles
===References===
#HE 6A/09: Papaxoinis G, Kotoula V, Giannoulatou E, Koliou GA, Karavasilis V, Lakis S, Koureas A, Bobos M, Chalaralambous E, Daskalaki E, Chatzopoulos K, Tsironis G, Pazarli E, Chrisafi S, Samantas E, Kaklamanos IG, Varthalitis I, Konstantara A, Syrigos KN, Pentheroudakis G, Pectasides D, Fountzilas G. Phase II study of panitumumab combined with capecitabine and oxaliplatin as first-line treatment in metastatic colorectal cancer patients: clinical results including extended tumor genotyping. Med Oncol. 2018 May 31;35(7):101. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01215539
==FOLFIRI==
FOLFIRI: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Van Cutsem et al. 2009 (CRYSTAL)	2004-07 to 2005-11 	Phase 3 (C)	FOLFIRI & Cetuximab	Shorter OS1
1Reported efficacy for CRYSTAL is based on the 2012 pooled update and is only for KRAS wild-type tumors.
====Biomarker eligibility criteria====
*CRYSTAL: none
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given first, with irinotecan
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given second (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given first, with leucovorin
14-day cycles
===References===
#CRYSTAL: Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00154102
##Update: Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Pooled update: Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. link to original article EuroPMC
##Biomarker analysis: Van Cutsem E, Lenz HJ, Köhne CH, Heinemann V, Tejpar S, Melezínek I, Beier F, Stroh C, Rougier P, van Krieken JH, Ciardiello F. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015 Mar 1;33(7):692-700. Epub 2015 Jan 20. link to original article EuroPMC
==FOLFIRI & Bevacizumab==
FOLFIRI & Bevacizumab: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan, Bevacizumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Heinemann et al. 2014 (FIRE-3)	2007-2012 	Phase 3 (E-switch-ic)	FOLFIRI & Cetuximab	Did not meet primary endpoint of ORR
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given first, with irinotecan
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given third (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given first, with leucovorin
====Targeted therapy====
*Bevacizumab (Avastin) 5 mg/kg IV once on day 1, given second
**In FIRE-3, initial infusion is over 90 minutes, next over 60 minutes, and subsequently over 30 minutes
14-day cycles
===References===
#FIRE-3: Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Müller S, Link H, Niederle N, Rost A, Höffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1065-75. Epub 2014 Jul 31.link to original article EuroPMC NCT00433927
==FOLFIRI & Cetuximab==
FOLFIRI & Cetuximab: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan, Cetuximab
===Regimen variant #1, 200 LCV===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Pinto et al. 2024 (ERMES)	2015-05 to 2020-03 	Phase 3 (C)	FOLFIRI & Cetuximab induction x 8, then Cetuximab maintenance	Inconclusive whether non-inferior PFS (co-primary endpoint)Median PFS: 12.2 vs 10 mo(HR 0.77, 95% CI 0.61-0.97)
====Biomarker eligibility criteria====
*ERMES: Wild-type RAS, Wild-type BRAF
====Chemotherapy====
*Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once on day 8
**Cycle 2 onwards: 250 mg/m2 IV once per day on days 1 & 8
14-day cycles
===Regimen variant #2, 400 LCV===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Van Cutsem et al. 2009 (CRYSTAL)	2004-07 to 2005-11 	Phase 3 (E-RT-esc) 	FOLFIRI 	Longer OS1 (secondary endpoint)Median OS: 23.5 vs 19.5 mo(HR 0.81, 95% CI 0.69-0.94)Seems to have longer PFS (primary endpoint)Median PFS: 8.9 vs 8 mo(aHR 0.85, 95% CI 0.72-0.99)
Heinemann et al. 2014 (FIRE-3) 	2007-2012 	Phase 3 (E-switch-ooc)	FOLFIRI & Bevacizumab	Did not meet primary endpoint of ORR
1Reported efficacy for CRYSTAL is based on the 2012 pooled update and is only for KRAS wild-type tumors.
====Biomarker eligibility criteria====
*CRYSTAL: none
*FIRE-3: Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given second, 1 hour after completion of cetuximab, with irinotecan
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given third (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given second, 1 hour after completion of cetuximab, with leucovorin
====Targeted therapy====
*Cetuximab (Erbitux) as follows, given first and completed at least 1 hour before FOLFIRI begins:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once on day 8
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1 & 8
14-day cycles
===References===
#CRYSTAL: Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00154102
##Update: Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Pooled update: Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. link to original article EuroPMC
##Biomarker analysis: Van Cutsem E, Lenz HJ, Köhne CH, Heinemann V, Tejpar S, Melezínek I, Beier F, Stroh C, Rougier P, van Krieken JH, Ciardiello F. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015 Mar 1;33(7):692-700. Epub 2015 Jan 20. link to original article EuroPMC
#FIRE-3: Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Müller S, Link H, Niederle N, Rost A, Höffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1065-75. Epub 2014 Jul 31. link to original article dosing details on CT.gov have been reviewed by our editors EuroPMC NCT00433927
#ERMES: Pinto C, Orlandi A, Normanno N, Maiello E, Calegari MA, Antonuzzo L, Bordonaro R, Zampino MG, Pini S, Bergamo F, Tonini G, Avallone A, Latiano TP, Rosati G, Cogoni AA, Ballestrero A, Zaniboni A, Roselli M, Tamberi S, Barone C. Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Versus Cetuximab as Maintenance Therapy in First-Line Therapy for RAS and BRAF Wild-Type Metastatic Colorectal Cancer: Phase III ERMES Study. J Clin Oncol. 2024 Apr 10;42(11):1278-1287. Epub 2024 Jan 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02484833
==FOLFIRI & Cetuximab (L-Leucovorin)==
FOLFIRI & Cetuximab: L-FOLinic acid (Leucovorin), Fluorouracil, IRInotecan, Cetuximab
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Van Cutsem et al. 2009 (CRYSTAL)	2004-07 to 2005-11 	Phase 3 (E-RT-esc)	FOLFIRI 	Longer OS1 (secondary endpoint)Median OS: 23.5 vs 19.5 mo(HR 0.81, 95% CI 0.69-0.94)
1Reported efficacy for CRYSTAL is based on the 2012 pooled update and is only for KRAS wild-type tumors.
====Biomarker eligibility criteria====
*CRYSTAL: none
====Chemotherapy====
*Levoleucovorin (Fusilev) 200 mg/m2 IV over 2 hours once on day 1, given second, 1 hour after completion of cetuximab, with irinotecan
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given third (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given second, 1 hour after completion of cetuximab, with L-leucovorin
====Targeted therapy====
*Cetuximab (Erbitux) as follows, given first and completed at least 1 hour before FOLFIRI begins:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once on day 8
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1 & 8
14-day cycles
===References===
#CRYSTAL: Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00154102
##Update: Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Pooled update: Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. link to original article EuroPMC
##Biomarker analysis: Van Cutsem E, Lenz HJ, Köhne CH, Heinemann V, Tejpar S, Melezínek I, Beier F, Stroh C, Rougier P, van Krieken JH, Ciardiello F. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015 Mar 1;33(7):692-700. Epub 2015 Jan 20. link to original article EuroPMC
==FOLFIRINOX==
FOLFIRINOX: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan, OXaliplatin
FOLFOXIRI: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, IRInotecan
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Modest et al. 2019 (VOLFI)	2011-2016 	Randomized Phase 2 (C)	FOLFOXIRI & Panitumumab	Lower ORR
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Fluorouracil (5-FU) 1600 mg/m2/day IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 3200 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 165 mg/m2 IV once on day 1
14-day cycle until POD or resectability or to max 12 cycles
===References===
#VOLFI: Modest DP, Martens UM, Riera-Knorrenschild J, Greeve J, Florschütz A, Wessendorf S, Ettrich T, Kanzler S, Nörenberg D, Ricke J, Seidensticker M, Held S, Buechner-Steudel P, Atzpodien J, Heinemann V, Seufferlein T, Tannapfel A, Reinacher-Schick AC, Geissler M. FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109). J Clin Oncol. 2019 Dec 10;37(35):3401-3411. Epub 2019 Oct 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01328171
==FOLFOX4==
FOLFOX4: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Bokemeyer et al. 2008 (OPUS) 	2005-2006 	Randomized Phase 2 (C)	FOLFOX4 & Cetuximab 	Shorter OS1
Douillard et al. 2010 (PRIME)	2006-2008 	Phase 3 (C) 	FOLFOX4 & Panitumumab	Seems to have shorter PFS2
Qin et al. 2018 (TAILOR-CRC) 	2010 to not reported	Phase 3 (C) 	FOLFOX4 & Cetuximab 	Seems to have shorter OS
1Reported efficacy for OPUS is based on the 2012 pooled update and is only for KRAS wild-type tumors.
2In PRIME, patients with KRAS wild-type tumors receiving this regimen seem to have shorter OS, based on the 2014 update. Conversely, in KRAS mutants, this regimen seemed to have longer PFS.
Note: TAILOR required RAS wild-type (not just KRAS). Note that there is another trial named TAILOR in non-small cell lung cancer, so this one has been dubbed TAILOR-CRC.
====Chemotherapy====
*Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, given first, with oxaliplatin on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus, given second (total dose per cycle: 2000 mg/m2)
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycles
===References===
#OPUS: Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009 Feb 10;27(5):663-71. Epub 2008 Dec 29. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00125034
##Update: Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol. 2011 Jul;22(7):1535-46. Epub 2011 Jan 12. link to original article EuroPMC
##Pooled update: Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. link to original article EuroPMC
#PRIME: Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. Epub 2010 Oct 4. link to original article EuroPMC NCT00364013
##Biomarker analysis: Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. link to original article EuroPMC
##Update: Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jul;25(7):1346-55. Epub 2014 Apr 8. link to original article EuroPMC
##HRQoL analysis: Siena S, Tabernero J, Bodoky G, Cunningham D, Rivera F, Ruff P, Canon JL, Koukakis R, Demonty G, Hechmati G, Douillard JY. Quality of life during first-line FOLFOX4±panitumumab in RAS wild-type metastatic colorectal carcinoma: results from a randomised controlled trial. ESMO Open. 2016 Mar 31;1(2):e000041. link to original article link to PMC article EuroPMC
#TAILOR-CRC: Qin S, Li J, Wang L, Xu J, Cheng Y, Bai Y, Li W, Xu N, Lin LZ, Wu Q, Li Y, Yang J, Pan H, Ouyang X, Qiu W, Wu K, Xiong J, Dai G, Liang H, Hu C, Zhang J, Tao M, Yao Q, Wang J, Chen J, Eggleton SP, Liu T. Efficacy and tolerability of first-line cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX-4) versus FOLFOX-4 in patients with RAS wild-type metastatic colorectal cancer: the open-label, randomized, phase III TAILOR trial. J Clin Oncol. 2018 Oct 20;36(30):3031-9. Epub 2018 Sep 10. link to original article does not contain dosing details in manuscript link to PMC article EuroPMC NCT01228734
==FOLFOX4 & Cetuximab==
FOLFOX4 & Cetuximab: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Cetuximab
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Bokemeyer et al. 2008 (OPUS)	2005-2006 	Randomized Phase 2 (E-esc)	FOLFOX4 	Longer OS1 (secondary endpoint)Median OS: 23.5 vs 19.5 mo(HR 0.81, 95% CI 0.69-0.94)Might have higher ORR (primary endpoint)
Qin et al. 2018 (TAILOR-CRC)	2010 to not reported	Phase 3 (E-esc) 	FOLFOX4 	Seems to have longer OS (secondary endpoint)Median OS: 20.7 vs 17.8 mo(HR 0.76, 95% CI 0.61-0.96)Longer PFS (primary endpoint)Median PFS: 9.2 vs 7.4 mo(HR 0.69, 95% CI 0.54-0.89)
1Reported efficacy for OPUS is based on the 2012 pooled update and is only for KRAS wild-type tumors.
TAILOR required RAS wild-type (not just KRAS). Note that there is another trial named TAILOR in non-small cell lung cancer, so this one has been dubbed TAILOR-CRC.
====Biomarker eligibility criteria====
*OPUS: none
*TAILOR-CRC: Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, given second, with oxaliplatin on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus, given third (total dose per cycle: 2000 mg/m2)
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given second
====Targeted therapy====
*Cetuximab (Erbitux) given first, as follows:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once on day 8
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1 & 8
14-day cycles
===References===
#OPUS: Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009 Feb 10;27(5):663-71. Epub 2008 Dec 29. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00125034
##Update: Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol. 2011 Jul;22(7):1535-46. Epub 2011 Jan 12. link to original article EuroPMC
##Pooled update: Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. link to original article EuroPMC
#TAILOR-CRC: Qin S, Li J, Wang L, Xu J, Cheng Y, Bai Y, Li W, Xu N, Lin LZ, Wu Q, Li Y, Yang J, Pan H, Ouyang X, Qiu W, Wu K, Xiong J, Dai G, Liang H, Hu C, Zhang J, Tao M, Yao Q, Wang J, Chen J, Eggleton SP, Liu T. Efficacy and tolerability of first-line cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX-4) versus FOLFOX-4 in patients with RAS wild-type metastatic colorectal cancer: the open-label, randomized, phase III TAILOR trial. J Clin Oncol. 2018 Oct 20;36(30):3031-9. Epub 2018 Sep 10. link to original article does not contain dosing details in manuscript link to PMC article EuroPMC NCT01228734
==FOLFOX4 & Panitumumab==
FOLFOX4 & Panitumumab: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Panitumumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Douillard et al. 2010 (PRIME)	2006-2008 	Phase 3 (E-RT-esc)	FOLFOX4 	Seems to have longer PFS (primary endpoint)Median PFS: 9.6 vs 8 mo(HR 0.80, 95% CI 0.66-0.97)Seems to have longer OS1 (secondary endpoint)Median OS: 23.8 vs 19.4 mo(HR 0.83, 95% CI 0.70-0.98)
1In KRAS wild-type patients, this regimen seemed to have longer OS, based on the exploratory analysis in the 2014 update.
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once per day on days 1 & 2
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
====Targeted therapy====
*Panitumumab (Vectibix) 6 mg/kg IV once on day 1, given first
**Infusion times are 1 hour for cycle 1, then if tolerated, 30 minutes for cycle 2 and later
14-day cycles
===References===
#PRIME: Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. Epub 2010 Oct 4. link to original article EuroPMC NCT00364013
##Biomarker analysis: Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. link to original article EuroPMC
##Update: Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jul;25(7):1346-55. Epub 2014 Apr 8. link to original article EuroPMC
##HRQoL analysis: Siena S, Tabernero J, Bodoky G, Cunningham D, Rivera F, Ruff P, Canon JL, Koukakis R, Demonty G, Hechmati G, Douillard JY. Quality of life during first-line FOLFOX4±panitumumab in RAS wild-type metastatic colorectal carcinoma: results from a randomised controlled trial. ESMO Open. 2016 Mar 31;1(2):e000041. link to original article link to PMC article EuroPMC
==mFOLFOX6-B==
mFOLFOX6-B: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Bevacizumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Venook et al. 2017 (CALGB 80405) 	2005-2012 	Phase 3 (E-switch-ic) 	1a. mFOLFOX6 & Cetuximab1b. FOLFIRI & Cetuximab 	Did not meet primary endpoint of OS
Venook et al. 2017 (CALGB 80405) 	2005-2012 	Phase 3 (E-switch-ic) 	2a. mFOLFOX6, Bevacizumab, Cetuximab2b. FOLFIRI, Bevacizumab, Cetuximab	Not reported
Schwartzberg et al. 2014 (PEAK) 	2009-2011 	Randomized Phase 2 (C)	mFOLFOX6 & Panitumumab 	Seems to have shorter PFS1
Watanabe et al. 2023 (PARADIGMCRC)	2015-05 to 2022-01 	Phase 3 (C) 	mFOLFOX6 & Panitumumab 	Seems to have shorter OS2Median OS: 34.3 vs 37.9 mo(HR 1.22, 95.8% CI 1.01-1.47)
1Reported efficacy for PEAK is based on the 2017 update.
2Reported efficacy is for patients with left-sided primary tumors, which was the primary analysis; efficacy results for the overall population were similar.
Note: In CALGB 80405, the arm receiving bevacizumab and cetuximab was terminated early.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
====Targeted therapy====
*Bevacizumab (Avastin) 5 mg/kg IV once on day 1
14-day cycles
===References===
#CALGB 80405: Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00265850
#PEAK: Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, Yu H, Oliner KS, Go WY. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014 Jul 20;32(21):2240-7. Epub 2014 Mar 31. link to original article EuroPMC NCT00819780
##Update: Rivera F, Karthaus M, Hecht JR, Sevilla I, Forget F, Fasola G, Canon JL, Guan X, Demonty G, Schwartzberg LS. Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017 Aug;32(8):1179-1190. Epub 2017 Apr 19. link to original article link to PMC article EuroPMC
#PARADIGMCRC: Watanabe J, Muro K, Shitara K, Yamazaki K, Shiozawa M, Ohori H, Takashima A, Yokota M, Makiyama A, Akazawa N, Ojima H, Yuasa Y, Miwa K, Yasui H, Oki E, Sato T, Naitoh T, Komatsu Y, Kato T, Hihara M, Soeda J, Misumi T, Yamamoto K, Akagi K, Ochiai A, Uetake H, Tsuchihara K, Yoshino T. Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2023 Apr 18;329(15):1271-1282. Erratum in: JAMA. 2023 Jun 27;329(24):2196. link to original article link to PMC article EuroPMC NCT02394795
==mFOLFOX6 & Cetuximab==
mFOLFOX6 & Cetuximab: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Cetuximab
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Venook et al. 2017 (CALGB 80405)	2005-2012 	Phase 3 (E-switch-ic) 	1a. mFOLFOX6-B1b. FOLFIRI & Bevacizumab 	Did not meet primary endpoint of OS
Venook et al. 2017 (CALGB 80405)	2005-2012 	Phase 3 (E-switch-ic) 	2a. mFOLFOX6, Bevacizumab, Cetuximab2b. FOLFIRI, Bevacizumab, Cetuximab	Not reported
Aranda et al. 2018 (MACRO-2) 	2010 to not reported	Non-randomized part of phase 2 RCT	 	
Note: In CALGB 80405, the arm receiving bevacizumab and cetuximab was terminated early.
====Biomarker eligibility criteria====
*CALGB 80405: Wild-type KRAS (codons 12 & 13)
*MACRO-2: Wild-type KRAS (exons 3 & 4), Wild-type NRAS (exons 2 to 4)
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) as follows, given first:
**Cycle 1: 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once on day 8
**Cycle 2 onwards: 250 mg/m2 IV once per day on days 1 & 8
14-day cycles (see below)
====Subsequent treatment====
*MACRO-2, after 8 cycles: continued mFOLFOX6 & Cetuximab until progression versus cetuximab maintenance
===References===
#CALGB 80405: Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00265850
#MACRO-2: Aranda E, García-Alfonso P, Benavides M, Sánchez Ruiz A, Guillén-Ponce C, Safont MJ, Alcaide J, Gómez A, López R, Manzano JL, Méndez Ureña M, Sastre J, Rivera F, Grávalos C, García T, Martín-Valadés JI, Falcó E, Navalón M, González Flores E, Ma García Tapiador A, Ma López Muñoz A, Barrajón E, Reboredo M, García Teijido P, Viudez A, Cárdenas N, Díaz-Rubio E; Spanish Cooperative Group for the Treatment of Digestive Tumours. First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: phase II randomised MACRO2 TTD study. Eur J Cancer. 2018 Sep;101:263-272. Epub 2018 Jul 24. link to original article EuroPMC NCT01161316
==mFOLFOX6 & Panitumumab==
mFOLFOX6 & Panitumumab: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Panitumumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Schwartzberg et al. 2014 (PEAK) 	2009-2011 	Randomized Phase 2 (E-switch-ooc)	mFOLFOX6-B 	Seems to have longer PFS1 (primary endpoint)Median PFS: 12.8 vs 10.1 mo(HR 0.68, 95% CI 0.48-0.96)Did not meet secondary endpoint of OS1Median OS: 36.9 vs 28.9 mo(HR 0.76, 95% CI 0.53-1.11)
Watanabe et al. 2023 (PARADIGMCRC)	2015-05 to 2022-01 	Phase 3 (E-switch-ooc) 	mFOLFOX6-B 	Seems to have longer OS2 (primary endpoint)Median OS: 37.9 vs 34.3 mo(HR 0.82, 95.798% CI 0.68-0.99)
Rossini et al. 2022 (TRIPLETE) 	2017-2021 	Phase 3 (C) 	mFOLFOXIRI & Panitumumab	Did not meet primary endpoint of ORR
1Reported efficacy for PEAK is based on the 2017 update.
2Reported efficacy is for patients with left-sided primary tumors, which was the primary analysis; efficacy results for the overall population were similar.
====Biomarker eligibility criteria====
*TRIPLETE: Wild-type KRAS (exons 2 to 4), wild-type NRAS (exons 2 to 4), wild-type BRAF codon 600
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, given third, then 2400 mg/m2 IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1, given second
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given second
====Targeted therapy====
*Panitumumab (Vectibix) 6 mg/kg IV over 30 to 60 minutes once on day 1, given first
14-day cycles
===References===
#PEAK: Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, Yu H, Oliner KS, Go WY. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014 Jul 20;32(21):2240-7. Epub 2014 Mar 31. link to original article EuroPMC NCT00819780
##Update: Rivera F, Karthaus M, Hecht JR, Sevilla I, Forget F, Fasola G, Canon JL, Guan X, Demonty G, Schwartzberg LS. Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017 Aug;32(8):1179-1190. Epub 2017 Apr 19. link to original article link to PMC article EuroPMC
#TRIPLETE: Rossini D, Antoniotti C, Lonardi S, Pietrantonio F, Moretto R, Antonuzzo L, Boccaccino A, Morano F, Brugia M, Pozzo C, Marmorino F, Bergamo F, Tamburini E, Passardi A, Randon G, Murgioni S, Borelli B, Buonadonna A, Giordano M, Fontanini G, Conca V, Formica V, Aglietta M, Bordonaro R, Aprile G, Masi G, Boni L, Cremolini C. Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO. J Clin Oncol. 2022 Sep 1;40(25):2878-2888. Epub 2022 Jun 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03231722
#PARADIGMCRC: Watanabe J, Muro K, Shitara K, Yamazaki K, Shiozawa M, Ohori H, Takashima A, Yokota M, Makiyama A, Akazawa N, Ojima H, Yuasa Y, Miwa K, Yasui H, Oki E, Sato T, Naitoh T, Komatsu Y, Kato T, Hihara M, Soeda J, Misumi T, Yamamoto K, Akagi K, Ochiai A, Uetake H, Tsuchihara K, Yoshino T. Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2023 Apr 18;329(15):1271-1282. Erratum in: JAMA. 2023 Jun 27;329(24):2196. link to original article link to PMC article EuroPMC NCT02394795
==mFOLFOXIRI & Cetuximab (L-Leucovorin)==
mFOLFOXIRI & Cetuximab: modified L-FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, IRInotecan, Cetuximab
===Regimen===
Study 	Dates of enrollment 	Evidence
Cremolini et al. 2018 (MACBETH)	2011-10-19 to 2015-03-01	Non-randomized part of phase 2 RCT
Note: 5-FU instructions were unusual in that no bolus was given.
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Fluorouracil (5-FU) 1200 mg/m2/day IV continuous infusion over 48 hours, started on day 1, given fourth (total dose per cycle: 2400 mg/m2)
*Levoleucovorin (Fusilev) 200 mg/m2 IV over 2 hours once on day 1, given third, with oxaliplatin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given third, with L-leucovorin
*Irinotecan (Camptosar) 130 mg/m2 IV over 60 minutes once on day 1, given second
====Targeted therapy====
*Cetuximab (Erbitux) 500 mg/m2 IV over 60 minutes once on day 1, given first
14-day cycle for 8 cycles
====Subsequent treatment====
*MACBETH, if deemed resectable: Surgery
*MACBETH, if deemed unresectable: Cetuximab versus bevacizumab maintenance
===References===
#MACBETH: Cremolini C, Antoniotti C, Lonardi S, Aprile G, Bergamo F, Masi G, Grande R, Tonini G, Mescoli C, Cardellino GG, Coltelli L, Salvatore L, Corsi DC, Lupi C, Gemma D, Ronzoni M, Dell'Aquila E, Marmorino F, Di Fabio F, Mancini ML, Marcucci L, Fontanini G, Zagonel V, Boni L, Falcone A. Activity and safety of cetuximab plus modified FOLFOXIRI followed by maintenance with cetuximab or bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer: a randomized phase 2 clinical trial. JAMA Oncol. 2018 Apr 1;4(4):529-536. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02295930
==FOLFOXIRI & Panitumumab==
FOLFOXIRI & Panitumumab: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, IRInotecan, Panitumumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Modest et al. 2019 (VOLFI)	2011-2016 	Randomized Phase 2 (E-esc)	FOLFOXIRI 	Higher ORR (primary endpoint)
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Chemotherapy====
*Fluorouracil (5-FU) 1500 mg/m2/day IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 3000 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 150 mg/m2 IV once on day 1
====Targeted therapy====
*Panitumumab (Vectibix) 6 mg/kg IV once on day 1
14-day cycle until POD or resectability or to max 12 cycles
===References===
#VOLFI: Modest DP, Martens UM, Riera-Knorrenschild J, Greeve J, Florschütz A, Wessendorf S, Ettrich T, Kanzler S, Nörenberg D, Ricke J, Seidensticker M, Held S, Buechner-Steudel P, Atzpodien J, Heinemann V, Seufferlein T, Tannapfel A, Reinacher-Schick AC, Geissler M. FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109). J Clin Oncol. 2019 Dec 10;37(35):3401-3411. Epub 2019 Oct 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01328171
=Maintenance after first-line therapy=
==Bevacizumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hagman et al. 2015 (Nordic ACT2)	2010-2012 	Phase 3 (C)	Erlotinib & Bevacizumab	Did not meet primary endpoint of PFS
====Biomarker eligibility criteria====
*Wild-type KRAS
====Targeted therapy====
*Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1
21-day cycles
===References===
#Nordic ACT2: Hagman H, Frödin JE, Berglund Å, Sundberg J, Vestermark LW, Albertsson M, Fernebro E, Johnsson A. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial. Ann Oncol. 2016 Jan;27(1):140-7. Epub 2015 Oct 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01229813
==Cetuximab monotherapy==
===Regimen variant #1, 250 mg/m2 weekly===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Aranda et al. 2018 (MACRO-2)	2010 to not reported	Randomized Phase 2 (E-de-esc)	mFOLFOX6 & Cetuximab	Non-inferior PFS9 (primary endpoint)
Note: regimen details are from ClinicalTrials.gov; they were not present in the abstract or the manuscript.
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Preceding treatment====
*First-line mFOLFOX6 & Cetuximab x 8
====Targeted therapy====
*Cetuximab (Erbitux) 250 mg/m2 IV once on day 1
7-day cycles
===Regimen variant #2, 500 mg/m2 q2wk===
Study 	Dates of enrollment 	Evidence
Cremolini et al. 2018 (MACBETH)	2011-10-19 to 2015-03-01	Randomized Phase 2
Note: this was a non-comparative study.
====Biomarker eligibility criteria====
*Wild-type KRAS, Wild-type NRAS
====Preceding treatment====
*First-line mFOLFOXIRI & Cetuximab x 8
====Targeted therapy====
*Cetuximab (Erbitux) 500 mg/m2 IV once on day 1
14-day cycles
===References===
#MACBETH: Cremolini C, Antoniotti C, Lonardi S, Aprile G, Bergamo F, Masi G, Grande R, Tonini G, Mescoli C, Cardellino GG, Coltelli L, Salvatore L, Corsi DC, Lupi C, Gemma D, Ronzoni M, Dell'Aquila E, Marmorino F, Di Fabio F, Mancini ML, Marcucci L, Fontanini G, Zagonel V, Boni L, Falcone A. Activity and safety of cetuximab plus modified FOLFOXIRI followed by maintenance with cetuximab or bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer: a randomized phase 2 clinical trial. JAMA Oncol. 2018 Apr 1;4(4):529-536. link to original article link to PMC article EuroPMC NCT02295930
#MACRO-2: Aranda E, García-Alfonso P, Benavides M, Sánchez Ruiz A, Guillén-Ponce C, Safont MJ, Alcaide J, Gómez A, López R, Manzano JL, Méndez Ureña M, Sastre J, Rivera F, Grávalos C, García T, Martín-Valadés JI, Falcó E, Navalón M, González Flores E, Ma García Tapiador A, Ma López Muñoz A, Barrajón E, Reboredo M, García Teijido P, Viudez A, Cárdenas N, Díaz-Rubio E; Spanish Cooperative Group for the Treatment of Digestive Tumours. First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: phase II randomised MACRO2 TTD study. Eur J Cancer. 2018 Sep;101:263-272. Epub 2018 Jul 24. link to original article EuroPMC NCT01161316
=Advanced or metastatic disease, second-line=
==FOLFIRI==
FOLFIRI: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Peeters et al. 2010 (20050181)	2006-2008 	Phase 3 (C)	FOLFIRI & Panitumumab	Seems to have shorter PFS1 (co-primary endpoint)Median PFS: 4.9 vs 6.7 mo(HR 1.22, 95% CI 1.03-1.45)
1Reported efficacy is for wild-type KRAS, only, and is based on the 2014 update.
====Biomarker eligibility criteria====
*None
====Prior treatment criteria====
*First-line fluoropyrimidine-based chemotherapy, with progression
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given first, with irinotecan
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given first, with leucovorin
14-day cycles
===References===
#20050181: Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00339183
##Update: Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tian Y, Sidhu R. Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jan;25(1):107-16. Erratum in: Ann Oncol. 2014 Mar;25(3):757. link to original article EuroPMC
==FOLFIRI & Panitumumab==
FOLFIRI & Panitumumab: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan, Panitumumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Peeters et al. 2010 (20050181)	2006-2008 	Phase 3 (E-esc)	FOLFIRI 	Seems to have longer PFS1 (co-primary endpoint)Median PFS: 6.7 vs 4.9 mo(HR 0.82, 95% CI 0.69-0.97)
1Reported efficacy is for wild-type KRAS, only, and is based on the 2014 update.
====Biomarker eligibility criteria====
*None
====Prior treatment criteria====
*First-line fluoropyrimidine-based chemotherapy, with progression
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given second, with irinotecan
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given third (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given second, with leucovorin
====Targeted therapy====
*Panitumumab (Vectibix) 6 mg/kg IV over 60 minutes once on day 1, given first
14-day cycles
===References===
#20050181: Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00339183
##Update: Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tian Y, Sidhu R. Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jan;25(1):107-16. Erratum in: Ann Oncol. 2014 Mar;25(3):757. link to original article EuroPMC
==Irinotecan monotherapy==
===Example orders===
*Example orders for Irinotecan (Camptosar) in colon cancer
===Regimen variant #1, 180 mg/m2 q2wk===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Shi et al. 2019 (CRC009)	2009-2011 	Phase 3 (C)	Irinotecan & CMAB009	Lower PFS50% (co-primary endpoint)
====Prior treatment criteria====
*Exposure to FOLFOX, with progression or discontinuation due to toxicity
====Chemotherapy====
*Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1
14-day cycles
===Regimen variant #2, 300 mg/m2 q3wk===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Seymour et al. 2013 (PICCOLO)	2006-12-04 to 2008-08-31	Phase 3 (C)	1. Irinotecan & Panitumumab 	Did not meet primary endpoint of OSMedian OS: 10.9 vs 10.4 mo(HR 0.99, 95% CI 0.81-1.20)
Seymour et al. 2013 (PICCOLO)	2006-12-04 to 2008-08-31	Phase 3 (C)	2. Irinotecan & Cyclosporine	Not reported
Note: In some trials, this starting dose was intended for patients who were at least 70 years old, had ECOG performance status 2 or more, or had prior pelvic radiation.
====Prior treatment criteria====
*First-line fluoropyrimidine-based chemotherapy, with progression
====Chemotherapy====
*Irinotecan (Camptosar) 300 mg/m2 IV over 90 minutes once on day 1
21-day cycles
===Regimen variant #3, 350 mg/m2 q3wk===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Seymour et al. 2013 (PICCOLO)	2006-12-04 to 2008-08-31	Phase 3 (C)	1. Irinotecan & Panitumumab 	Did not meet primary endpoint of OSMedian OS: 10.9 vs 10.4 mo(HR 0.99, 95% CI 0.81-1.20)
Seymour et al. 2013 (PICCOLO)	2006-12-04 to 2008-08-31	Phase 3 (C)	2. Irinotecan & Cyclosporine	Not reported
====Prior treatment criteria====
*First-line fluoropyrimidine-based chemotherapy, with progression
====Chemotherapy====
*Irinotecan (Camptosar) 350 mg/m2 IV over 90 minutes once on day 1
====Supportive therapy====
*(varied depending on reference):
*"Standard regimens of antiemetics, Atropine (Atropen), and intensive Loperamide (Imodium)," but no prophylactic Atropine (Atropen) allowed on cycle 1 day 1
21-day cycles
===References===
#PICCOLO: Seymour MT, Brown SR, Middleton G, Maughan T, Richman S, Gwyther S, Lowe C, Seligmann JF, Wadsley J, Maisey N, Chau I, Hill M, Dawson L, Falk S, O'Callaghan A, Benstead K, Chambers P, Oliver A, Marshall H, Napp V, Quirke P. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol. 2013 Jul;14(8):749-59. Epub 2013 May 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00389870
#CRC009: Shi Y, Li J, Xu J, Sun Y, Wang L, Cheng Y, Liu W, Sun G, Chen Y, Bai L, Zhang Y, He X, Luo Y, Wang Z, Liu Y, Yao Q, Li Y, Qin S, Hu X, Bi F, Zheng R, Ouyang X. CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients: promising findings from a prospective, open-label, randomized, phase III trial. Cancer Commun (Lond). 2019 May 24;39(1):28. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01550055
==Irinotecan & Cetuximab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Sobrero et al. 2008 (EPIC)	2003-2006 	Phase 3 (E-esc)	Irinotecan	Did not meet primary endpoint of OS
====Prior treatment criteria====
*First-line fluoropyrimidine and oxaliplatin treatment, with progression or discontinuation due to toxicity 
====Chemotherapy====
*Irinotecan (Camptosar) by the following criteria:
**Standard patients: 350 mg/m2 IV over 90 minutes once on day 1
**If aged 70 years old or more, ECOG performance status 2 or more, or prior pelvic radiation: 300 mg/m2 IV over 90 minutes once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8 & 15
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
====Supportive therapy====
*Antihistamine prior to at least the first infusion of cetuximab
21-day cycles
===References===
#EPIC: Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kröning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA 3rd. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008 May 10;26(14):2311-9. Epub 2008 Apr 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00063141
=Advanced or metastatic disease, subsequent lines of therapy=
==Cetuximab monotherapy==
===Example orders===
*Example orders for Cetuximab (Erbitux) in colon cancer
===Regimen variant #1, weekly===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Saltz et al. 2004 	2001 	Phase 2 (RT) 	 	
Cunningham et al. 2004 (BOND) 	2001-07 to 2002-05 	Phase 3 (C) 	Irinotecan & Cetuximab	Shorter TTP
Lenz et al. 2006 (SALVAGE) 	Not reported 	Phase 2 	 	
Jonker et al. 2007 (NCIC-CTG CO.17) 	2003-2005 	Phase 3 (E-RT-esc)	Best supportive care 	Longer OS (primary endpoint)Median OS: 6.1 vs 4.6 mo(HR 0.77, 95% CI 0.64-0.92)
Siu et al. 2013 (NCIC-CTG/AGITG CO.20)	2008-2011 	Phase 3 (C) 	Brivanib & Cetuximab 	Might have shorter OS (primary endpoint)Median OS: 8.1 vs 8.8 mo(HR 1.14, 95% CI 0.97-1.35)
Price et al. 2014 (ASPECCT) 	2010-2012 	Phase 3 (C) 	Panitumumab 	Non-inferior OSMedian OS: 10 vs 10.4 mo(HR 1.03, 95% CI 0.90-1.19)
====Prior treatment criteria====
*Saltz et al. 2004: Exposure to irinotecan-containing therapy, with clinical failure
*BOND: Exposure to irinotecan-containing therapy, with progression
*SALVAGE: Exposure to irinotecan, oxaliplatin, and a fluoropyrimidine
*NCIC-CTG CO.17: Exposure to irinotecan, oxaliplatin, and a fluoropyrimidine or contraindication to these drugs
*NCIC-CTG/AGITG CO.20: Exposure to a fluoropyrimidine and exposure to irinotecan and oxaliplatin or contraindication to these drugs
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once on day 1
====Supportive therapy====
*Varies depending on reference
*Antihistamine (such as Diphenhydramine (Benadryl) 50 mg IV) prior to at least the first infusion of cetuximab
7-day cycles
===Regimen variant #2, bi-weekly===
Study 	Dates of enrollment	Evidence
Tabernero et al. 2009	2004-09 to 2006-08 	Phase 1
Note: no primary reference could be found for this exact dosing in monotherapy; in the phase I trial it is described as "the most convenient and feasible dose".
====Targeted therapy====
*Cetuximab (Erbitux) 500 mg/m2 IV over 2 hours once on day 1
**If tolerated, subsequent doses can be given over 1 hour
====Supportive therapy====
*Antihistamine prior to cetuximab
14-day cycles
===References===
#Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004 Apr 1;22(7):1201-8. Epub 2004 Mar 1. link to original article EuroPMC
#BOND: Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#SALVAGE: Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, Mirtsching B, Cohn AL, Pippas AW, Azarnia N, Tsuchihashi Z, Mauro DJ, Rowinsky EK. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol. 2006 Oct 20;24(30):4914-21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#NCIC-CTG CO.17: Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00079066
##Subgroup analysis: Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65. link to original article EuroPMC
##Subgroup analysis: Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, Pavlakis N, Gibbs P, Zhu L, Dueck DA, Whittom R, Langer C, O'Callaghan CJ. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC-CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol. 2011 Jan;22(1):118-26. Epub 2010 Jul 5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Phase I: Tabernero J, Ciardiello F, Rivera F, Rodriguez-Braun E, Ramos FJ, Martinelli E, Vega-Villegas ME, Roselló S, Liebscher S, Kisker O, Macarulla T, Baselga J, Cervantes A. Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Ann Oncol. 2010 Jul;21(7):1537-45. Epub 2009 Nov 25. link to original article EuroPMC
#NCIC-CTG/AGITG CO.20: Siu LL, Shapiro JD, Jonker DJ, Karapetis CS, Zalcberg JR, Simes J, Couture F, Moore MJ, Price TJ, Siddiqui J, Nott LM, Charpentier D, Liauw W, Sawyer MB, Jefford M, Magoski NM, Haydon A, Walters I, Ringash J, Tu D, O'Callaghan CJ. Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: the NCIC Clinical Trials Group and AGITG CO.20 Trial. J Clin Oncol. 2013 Jul 1;31(19):2477-84. Epub 2013 May 20. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00640471
##HRQoL analysis: Ringash J, Au HJ, Siu LL, Shapiro JD, Jonker DJ, Zalcberg JR, Moore MJ, Strickland A, Kotb R, Jeffery M, Alcindor T, Ng S, Salim M, Sabesan S, Easaw JC, Shannon J, El-Tahche F, Walters I, Tu D, O'Callaghan CJ; NCIC Clinical Trials Group; Australasian Gastrointestinal Trials Group. Quality of life in patients with K-RAS wild-type colorectal cancer: the CO.20 phase 3 randomized trial. Cancer. 2014 Jan 15;120(2):181-9. Epub 2013 Oct 11. link to original article EuroPMC
#ASPECCT: Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, Murugappan S, Sidhu R. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014 May;15(6):569-79. Epub 2014 Apr 14. link to original article EuroPMC NCT01001377
##Update: Price T, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Guan X, Peeters M. Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer. Eur J Cancer. 2016 Nov;68:51-59. Epub 2016 Oct 5. link to original article EuroPMC
==Irinotecan & Cetuximab==
===Regimen variant #1, 125/250, irinotecan 2 weeks on, 1 week off===
FDA-recommended dose
Note: In contrast to BOND, some guidelines list irinotecan as being given on days 1 & 8 of a 21-day cycle. No primary reference could be found for this. Note also that the FDA-recommended dosing is for the cetuximab component; no comment is made about irinotecan dosing.
====Chemotherapy====
*Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1 & 8
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8 & 15
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
====Supportive therapy====
*Antihistamine prior to at least the first infusion of cetuximab
21-day cycles
===Regimen variant #2, 125/250, irinotecan 4 weeks on, 2 weeks off===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Cunningham et al. 2004 (BOND)	2001-07 to 2002-05 	Phase 3 (E-RT-esc)	Cetuximab 	Longer TTP (secondary endpoint)Higher ORR (primary endpoint)
Note that the FDA-recommended dosing is for the cetuximab component; no comment is made about irinotecan dosing.
====Prior treatment criteria====
*BOND: Exposure to irinotecan-containing therapy, with progression
====Chemotherapy====
*Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 15, 22
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8, 15, 22, 29, 36
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
====Supportive therapy====
*Antihistamine prior to at least the first infusion of cetuximab
42-day cycles
===Regimen variant #3, 150/500, bi-weekly===
Study 	Dates of enrollment	Evidence
Osumi et al. 2018	2011-2014 	Phase 2
====Prior treatment criteria====
*Exposure to fluoropyrimidine‐ and oxaliplatin‐based chemotherapy, with treatment failure
====Chemotherapy====
*Irinotecan (Camptosar) 150 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) 500 mg/m2 IV over 2 hours once on day 1
**Subsequent doses are given over 60 minutes
====Supportive therapy====
*Antihistamine prior to cetuximab
14-day cycles
===Regimen variant #4, 180/250, bi-weekly, with response adaptation===
Study 	Dates of enrollment	Evidence
Van Cutsem et al. 2012 (EVEREST)	2004-2005 	Non-randomized part of phase 1/2 RCT
====Prior treatment criteria====
*Exposure to irinotecan-containing chemotherapy
====Chemotherapy====
*Irinotecan (Camptosar) 180 mg/m2 IV over 30 minutes once per day on days 1 & 15
====Targeted therapy====
*Cetuximab (Erbitux) 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once per day on days 8 & 15
21-day course
====Subsequent treatment====
*EVEREST, grade 0 or 1 skin reaction: Standard-dose Irinotecan & Cetuximab continuation vs escalate to Irinotecan & Cetuximab; cetuximab 500 mg/m2
*EVEREST, grade 2 or worse skin reaction: Continue standard-dose Irinotecan & Cetuximab
===Regimen variant #5, 180/500, bi-weekly===
Study 	Dates of enrollment	Evidence
Martín-Martorell et al. 2008	2005-2007 	Phase 2
====Prior treatment criteria====
*One previous line of chemotherapy
====Chemotherapy====
*Irinotecan (Camptosar) 180 mg/m2 IV over 30 minutes once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) 500 mg/m2 IV over 2 hours once on day 1
**If tolerated, subsequent doses can be given over 1 hour
====Supportive therapy====
*Antihistamine prior to cetuximab
*Dexamethasone (Decadron) & Ondansetron (Zofran) prior to irinotecan
14-day cycles
===Regimen variant #6, 350/250, q3wk irinotecan===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Cunningham et al. 2004 (BOND)	2001-07 to 2002-05 	Phase 3 (E-RT-esc)	Cetuximab 	Longer TTP (secondary endpoint)Higher ORR (primary endpoint)
Note that the FDA-recommended dosing is for the cetuximab component; no comment is made about irinotecan dosing.
====Prior treatment criteria====
*BOND: Exposure to irinotecan-containing therapy, with progression
====Chemotherapy====
*Irinotecan (Camptosar) by the following criteria:
**Standard patients: 350 mg/m2 IV over 90 minutes once on day 1
**If aged 70 years old or more, ECOG performance status 2 or more, or prior pelvic radiation: 300 mg/m2 IV over 90 minutes once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8 & 15
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
====Supportive therapy====
*Antihistamine prior to at least the first infusion of cetuximab
21-day cycles
===References===
#BOND: Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Martín-Martorell P, Roselló S, Rodríguez-Braun E, Chirivella I, Bosch A, Cervantes A. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer. 2008 Aug 5;99(3):455-8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
#EVEREST: Van Cutsem E, Tejpar S, Vanbeckevoort D, Peeters M, Humblet Y, Gelderblom H, Vermorken JB, Viret F, Glimelius B, Gallerani E, Hendlisz A, Cats A, Moehler M, Sagaert X, Vlassak S, Schlichting M, Ciardiello F. Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol. 2012 Aug 10;30(23):2861-8. Epub 2012 Jul 2. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#Osumi H, Shinozaki E, Mashima T, Wakatsuki T, Suenaga M, Ichimura T, Ogura M, Ota Y, Nakayama I, Takahari D, Chin K, Miki Y, Yamaguchi K. Phase II trial of biweekly cetuximab and irinotecan as third-line therapy for pretreated KRAS exon 2 wild-type colorectal cancer. Cancer Sci. 2018 Aug;109(8):2567-2575. Epub 2018 Jul 13. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000019893
==Panitumumab monotherapy==
===Example orders===
*Example orders for Panitumumab (Vectibix) in colon cancer
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Van Cutsem et al. 2007 (20020408)	2004-01 to 2005-06 	Phase 3 (E-RT-esc) 	Best supportive care	Longer PFS (primary endpoint)Median PFS: 8 vs 7.3 wks(HR 0.54, 95% CI 0.44-0.66)
Price et al. 2014 (ASPECCT) 	2010-2012 	Phase 3 (E-RT-switch-ic)	Cetuximab 	Non-inferior OS (primary endpoint)Median OS: 10.4 vs 10 mo(HR 0.97, 95% CI 0.84-1.11)
Kim et al. 2016 (20100007) 	2011-2013 	Phase 3 (E-RT-esc) 	Best supportive care	Longer OS (primary endpoint)1Median OS: 10 vs 6.9 mo(HR 0.72, 95% CI 0.55-0.94)
1Reported efficacy for 20100007 is based on the 2018 update.
====Prior treatment criteria====
*20020408 & 20100007: Exposure to irinotecan, oxaliplatin, and a fluoropyrimidine
====Targeted therapy====
*Panitumumab (Vectibix) 6 mg/kg IV over 60 minutes once on day 1
14-day cycles
===References===
#20020408: Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007 May 1;25(13):1658-64. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00113763
##HRQoL analysis: Odom D, Barber B, Bennett L, Peeters M, Zhao Z, Kaye J, Wolf M, Wiezorek J. Health-related quality of life and colorectal cancer-specific symptoms in patients with chemotherapy-refractory metastatic disease treated with panitumumab. Int J Colorectal Dis. 2011 Feb;26(2):173-81. Epub 2010 Dec 29. link to original article link to PMC article EuroPMC
#ASPECCT: Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, Murugappan S, Sidhu R. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014 May;15(6):569-79. Epub 2014 Apr 14. link to original article EuroPMC NCT01001377
##Update: Price T, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Guan X, Peeters M. Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer. Eur J Cancer. 2016 Nov;68:51-59. Epub 2016 Oct 5. link to original article EuroPMC
#20100007: Kim TW, Elme A, Kusic Z, Park JO, Udrea AA, Kim SY, Ahn JB, Valencia RV, Krishnan S, Bilic A, Manojlovic N, Dong J, Guan X, Lofton-Day C, Jung AS, Vrdoljak E. A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer. Br J Cancer. 2016 Nov 8;115(10):1206-1214. Epub 2016 Oct 13. link to original article link to PMC article EuroPMC NCT01412957
##Update: Kim TW, Elme A, Park JO, Udrea AA, Kim SY, Ahn JB, Valencia RV, Krishnan S, Manojlovic N, Guan X, Lofton-Day C, Jung AS, Vrdoljak E. Final Analysis of Outcomes and RAS/BRAF Status in a Randomized Phase 3 Study of Panitumumab and Best Supportive Care in Chemorefractory Wild Type KRAS Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2018 Sep;17(3):206-214. Epub 2018 Mar 21. link to original article EuroPMC
Category:Colorectal cancer regimens
Category:Biomarker-specific pages
Category:Gastrointestinal cancers