Non-small cell lung cancer, ALK-positive - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the ALK+ NSCLC page for current regimens.
Last updated on TBA:TBA regimens on this page
TBA variants on this page
=Adjuvant therapy=
==Carboplatin & Gemcitabine (GCb)==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wu et al. 2024 (ALINA)	2018-08 to 2021-12 	Phase 3 (C)	Alectinib 	Shorter DFSDFS24: 63.7% vs 93.6%(HR 4.17, 95% CI 2.33-7.69)
====Preceding treatment====
*Resection
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
===References===
#ALINA: Wu YL, Dziadziuszko R, Ahn JS, Barlesi F, Nishio M, Lee DH, Lee JS, Zhong W, Horinouchi H, Mao W, Hochmair M, de Marinis F, Migliorino MR, Bondarenko I, Lu S, Wang Q, Ochi Lohmann T, Xu T, Cardona A, Ruf T, Noe J, Solomon BJ; ALINA Investigators. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Apr 11;390(14):1265-1276. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03456076
==Carboplatin & Pemetrexed==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wu et al. 2024 (ALINA)	2018-08 to 2021-12 	Phase 3 (C)	Alectinib 	Shorter DFSDFS24: 63.7% vs 93.6%(HR 4.17, 95% CI 2.33-7.69)
====Preceding treatment====
*Resection
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
*Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
===References===
#ALINA: Wu YL, Dziadziuszko R, Ahn JS, Barlesi F, Nishio M, Lee DH, Lee JS, Zhong W, Horinouchi H, Mao W, Hochmair M, de Marinis F, Migliorino MR, Bondarenko I, Lu S, Wang Q, Ochi Lohmann T, Xu T, Cardona A, Ruf T, Noe J, Solomon BJ; ALINA Investigators. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Apr 11;390(14):1265-1276. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03456076
==Carboplatin & Vinorelbine==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wu et al. 2024 (ALINA)	2018-08 to 2021-12 	Phase 3 (C)	Alectinib 	Shorter DFSDFS24: 63.7% vs 93.6%(HR 4.17, 95% CI 2.33-7.69)
====Preceding treatment====
*Resection
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
*Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
===References===
#ALINA: Wu YL, Dziadziuszko R, Ahn JS, Barlesi F, Nishio M, Lee DH, Lee JS, Zhong W, Horinouchi H, Mao W, Hochmair M, de Marinis F, Migliorino MR, Bondarenko I, Lu S, Wang Q, Ochi Lohmann T, Xu T, Cardona A, Ruf T, Noe J, Solomon BJ; ALINA Investigators. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Apr 11;390(14):1265-1276. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03456076
==Cisplatin & Gemcitabine (GC)==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wu et al. 2024 (ALINA)	2018-08 to 2021-12 	Phase 3 (C)	Alectinib 	Shorter DFSDFS24: 63.7% vs 93.6%(HR 4.17, 95% CI 2.33-7.69)
====Preceding treatment====
*Resection
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
===References===
#ALINA: Wu YL, Dziadziuszko R, Ahn JS, Barlesi F, Nishio M, Lee DH, Lee JS, Zhong W, Horinouchi H, Mao W, Hochmair M, de Marinis F, Migliorino MR, Bondarenko I, Lu S, Wang Q, Ochi Lohmann T, Xu T, Cardona A, Ruf T, Noe J, Solomon BJ; ALINA Investigators. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Apr 11;390(14):1265-1276. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03456076
==Cisplatin & Pemetrexed==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wu et al. 2024 (ALINA)	2018-08 to 2021-12 	Phase 3 (C)	Alectinib 	Shorter DFSDFS24: 63.7% vs 93.6%(HR 4.17, 95% CI 2.33-7.69)
====Preceding treatment====
*Resection
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
===References===
#ALINA: Wu YL, Dziadziuszko R, Ahn JS, Barlesi F, Nishio M, Lee DH, Lee JS, Zhong W, Horinouchi H, Mao W, Hochmair M, de Marinis F, Migliorino MR, Bondarenko I, Lu S, Wang Q, Ochi Lohmann T, Xu T, Cardona A, Ruf T, Noe J, Solomon BJ; ALINA Investigators. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Apr 11;390(14):1265-1276. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03456076
==Cisplatin & Vinorelbine (CVb)==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wu et al. 2024 (ALINA)	2018-08 to 2021-12 	Phase 3 (C)	Alectinib 	Shorter DFSDFS24: 63.7% vs 93.6%(HR 4.17, 95% CI 2.33-7.69)
====Preceding treatment====
*Resection
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
===References===
#ALINA: Wu YL, Dziadziuszko R, Ahn JS, Barlesi F, Nishio M, Lee DH, Lee JS, Zhong W, Horinouchi H, Mao W, Hochmair M, de Marinis F, Migliorino MR, Bondarenko I, Lu S, Wang Q, Ochi Lohmann T, Xu T, Cardona A, Ruf T, Noe J, Solomon BJ; ALINA Investigators. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Apr 11;390(14):1265-1276. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03456076
=Advanced or metastatic disease, ALK inhibitor-naive=
==Carboplatin & Pemetrexed==
CP: Carboplatin & Pemetrexed
Carbo-Pem: Carboplatin & Pemetrexed
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Solomon et al. 2014 (PROFILE 1014)	2011-2013 	Phase 3 (C)	Crizotinib	Shorter PFSMedian PFS: 7 vs 10.9 mo(HR 2.22, 95% CI 1.67-2.86)Might have shorter OS1Median OS: 47.5 vs NYR mo(HR 1.32, 95% CI 0.95-1.82)
Wu et al. 2018 (PROFILE 1029) 	2012-2014 	Phase 3 (C)	Crizotinib	Shorter PFSMedian PFS: 6.8 vs 11.1 mo(HR 2.50, 95% CI 1.77-3.45)
Soria et al. 2017 (ASCEND-4) 	2013-2015 	Phase 3 (C)	Ceritinib 	Shorter PFSMedian PFS: 8.1 vs 16.6 mo(HR 1.82, 95% CI 1.37-2.38)
1Reported OS efficacy for PROFILE 1014 is based on the 2018 update.
====Biomarker eligibility criteria====
*Biomarker: ALK Fusion Gene Rearrangement
*Diagnostics: IHC
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 or 6 IV over 15 to 60 minutes once on day 1, given second
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
====Supportive therapy====
*Dexamethasone (Decadron) 4 mg or equivalent corticosteroid PO twice per day on the day before, the day of, and day after each dose of pemetrexed
*Folic acid (Folate) 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of pemetrexed, to be taken throughout pemetrexed therapy
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of pemetrexed, to be given throughout pemetrexed therapy
21-day cycle for varying durations: 4 cycles (ASCEND-4); 6 cycles (PROFILE 1014, PROFILE 1029)
====Subsequent treatment====
*ASCEND-4: Pemetrexed maintenance
===References===
# PROFILE 1014: Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. Erratum in: N Engl J Med. 2015 Oct 15;373(16):1582. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01154140
## Subgroup analysis: Solomon BJ, Cappuzzo F, Felip E, Blackhall FH, Costa DB, Kim DW, Nakagawa K, Wu YL, Mekhail T, Paolini J, Tursi J, Usari T, Wilner KD, Selaru P, Mok TS. Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non-small-cell lung cancer: results from PROFILE 1014. J Clin Oncol. 2016 Aug 20;34(24):2858-65. Epub 2016 Mar 28. link to original article EuroPMC
## Pooled subgroup analysis: Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. link to original article link to PMC article EuroPMC
## Update: Solomon BJ, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Tang Y, Wilner KD, Blackhall F, Mok TS. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018 Aug 1;36(22):2251-2258. Epub 2018 May 16. link to original article EuroPMC
# ASCEND-4: Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4;389(10072):917-929. Epub 2017 Jan 24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01828099
# PROFILE 1029: Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, Ho JCM, Ong CK, Tsai CM, Chung CH, Wilner KD, Tang Y, Masters ET, Selaru P, Mok TS. Results of PROFILE 1029, a phase III comparison of first-line crizotinib versus chemotherapy in East Asian patients with ALK-positive advanced non-small cell lung cancer. J Thorac Oncol. 2018 Oct;13(10):1539-1548. Epub 2018 Aug 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01639001
==Cisplatin & Pemetrexed==
Pem-Cis: Pemetrexed & Cisplatin
Cis-Pem: Cisplatin & Pemetrexed
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Solomon et al. 2014 (PROFILE 1014)	2011-2013 	Phase 3 (C)	Crizotinib	Shorter PFSMedian PFS: 7 vs 10.9 mo(HR 2.22, 95% CI 1.67-2.86)Might have shorter OS1Median OS: 47.5 vs NYR mo(HR 1.32, 95% CI 0.95-1.82)
Wu et al. 2018 (PROFILE 1029) 	2012-2014 	Phase 3 (C)	Crizotinib	Shorter PFSMedian PFS: 6.8 vs 11.1 mo(HR 2.50, 95% CI 1.77-3.45)
Soria et al. 2017 (ASCEND-4) 	2013-2015 	Phase 3 (C)	Ceritinib 	Shorter PFSMedian PFS: 8.1 vs 16.6 mo(HR 1.82, 95% CI 1.37-2.38)
1Reported OS efficacy for PROFILE 1014 is based on the 2018 update.
====Biomarker eligibility criteria====
Biomarker: ALK Fusion Gene Rearrangement
Diagnostics: FISH or IHC
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1, given second
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
====Supportive therapy====
*(as described in JMDB):
*Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to pemetrexed
*Folic acid (Folate) 1 mg PO once per day
*In Sequist et al. 2013: Patients "received Folic acid (Folate), vitamin B12, and dexamethasone, as per package recommendations for pemetrexed."
21-day cycle for varying durations: 4 cycles (ASCEND-4); 6 cycles (PROFILE 1014, PROFILE 1029)
====Subsequent treatment====
*ASCEND-4: Pemetrexed maintenance
===References===
# PROFILE 1014: Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. Erratum in: N Engl J Med. 2015 Oct 15;373(16):1582. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01154140
## Subgroup analysis: Solomon BJ, Cappuzzo F, Felip E, Blackhall FH, Costa DB, Kim DW, Nakagawa K, Wu YL, Mekhail T, Paolini J, Tursi J, Usari T, Wilner KD, Selaru P, Mok TS. Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non-small-cell lung cancer: results from PROFILE 1014. J Clin Oncol. 2016 Aug 20;34(24):2858-65. Epub 2016 Mar 28. link to original article EuroPMC
## Pooled subgroup analysis: Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. link to original article link to PMC article EuroPMC
## Update: Solomon BJ, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Tang Y, Wilner KD, Blackhall F, Mok TS. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018 Aug 1;36(22):2251-2258. Epub 2018 May 16. link to original article EuroPMC
# ASCEND-4: Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4;389(10072):917-929. Epub 2017 Jan 24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01828099
# PROFILE 1029: Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, Ho JCM, Ong CK, Tsai CM, Chung CH, Wilner KD, Tang Y, Masters ET, Selaru P, Mok TS. Results of PROFILE 1029, a phase III comparison of first-line crizotinib versus chemotherapy in East Asian patients with ALK-positive advanced non-small cell lung cancer. J Thorac Oncol. 2018 Oct;13(10):1539-1548. Epub 2018 Aug 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01639001
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Shaw et al. 2013 (PROFILE 1007)	2010-2012 	Phase 3 (C)	Crizotinib	Shorter PFSMedian PFS: 3 vs 7.7 mo(HR 2.04, 95% CI 1.56-2.70)
====Biomarker eligibility criteria====
Biomarker: ALK Fusion Gene Rearrangement
Diagnostics: FISH
====Chemotherapy====
*Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
====Supportive therapy====
*Per JMEI: Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2 (3 days)
21-day cycles
===References===
# PROFILE 1007: Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors EuroPMC NCT00932893
##PRO analysis: Blackhall F, Kim DW, Besse B, Nokihara H, Han JY, Wilner KD, Reisman A, Iyer S, Hirsh V, Shaw AT. Patient-reported outcomes and quality of life in PROFILE 1007: a randomized trial of crizotinib compared with chemotherapy in previously treated patients with ALK-positive advanced non-small-cell lung cancer. J Thorac Oncol. 2014 Nov;9(11):1625-33. Erratum in: J Thorac Oncol. 2015 Nov;10(11):1657. link to original article EuroPMC
## Pooled subgroup analysis: Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. link to original article link to PMC article EuroPMC
==Pemetrexed monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Shaw et al. 2013 (PROFILE 1007)	2010-2012 	Phase 3 (C)	Crizotinib	Shorter PFSMedian PFS: 3 vs 7.7 mo(HR 2.04, 95% CI 1.56-2.70)
====Biomarker eligibility criteria====
*Biomarker: ALK Fusion Gene Rearrangement
*Diagnostics: FISH 
====Chemotherapy====
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
====Supportive therapy====
*(per Ardizzoni et al. 2012):
*Dexamethasone (Decadron) 4 mg or equivalent corticosteroid PO twice per day on the day before, the day of, and day after each dose of pemetrexed
*Folic acid (Folate) 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of pemetrexed, to be taken throughout pemetrexed therapy
**JMEI used Folic acid (Folate) 1 mg PO once per day
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of pemetrexed, to be given throughout pemetrexed therapy
21-day cycles 
===References===
# PROFILE 1007: Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors EuroPMC NCT00932893
##PRO analysis: Blackhall F, Kim DW, Besse B, Nokihara H, Han JY, Wilner KD, Reisman A, Iyer S, Hirsh V, Shaw AT. Patient-reported outcomes and quality of life in PROFILE 1007: a randomized trial of crizotinib compared with chemotherapy in previously treated patients with ALK-positive advanced non-small-cell lung cancer. J Thorac Oncol. 2014 Nov;9(11):1625-33. Erratum in: J Thorac Oncol. 2015 Nov;10(11):1657. link to original article EuroPMC
## Pooled subgroup analysis: Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. link to original article link to PMC article EuroPMC
=Advanced or metastatic disease, ALK inhibitor-exposed=
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Shaw et al. 2017 (ASCEND-5)	2013-2015 	Phase 3 (C)	Ceritinib 	Shorter PFSMedian PFS: 1.6 vs 5.4 mo(HR 2.04, 95% CI 1.49-2.78)
Novello et al. 2018 (ALUR) 	2015-2018 	Phase 3 (C)	Alectinib 	Shorter PFS1Median PFS: 1.4 vs 10.9 mo(HR 5.00, 95% CI 3.03-8.33)
1Reported efficacy for ALUR is based on the 2022 update.
====Biomarker eligibility criteria====
*Biomarker: ALK Fusion Gene Rearrangement
*Diagnostics: FISH or IHC
====Chemotherapy====
*Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
====Supportive therapy====
*Per JMEI: Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2 (3 days)
21-day cycles
===References===
# ASCEND-5: Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886. Epub 2017 Jun 9. link to original articledosing details in manuscript have been reviewed by our editorsEuroPMC NCT01828112
# ALUR: Novello S, Mazières J, Oh IJ, de Castro J, Migliorino MR, Helland Å, Dziadziuszko R, Griesinger F, Kotb A, Zeaiter A, Cardona A, Balas B, Johannsdottir HK, Das-Gupta A, Wolf J. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018 Jun 1;29(6):1409-1416. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02604342
##Update: Wolf J, Helland Å, Oh IJ, Migliorino MR, Dziadziuszko R, Wrona A, de Castro J, Mazieres J, Griesinger F, Chlistalla M, Cardona A, Ruf T, Trunzer K, Smoljanovic V, Novello S. Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer. ESMO Open. 2022 Feb;7(1):100333. Epub 2022 Jan 15. link to original article link to PMC article EuroPMC
==Pemetrexed monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Shaw et al. 2017 (ASCEND-5)	2013-2015 	Phase 3 (C)	Ceritinib 	Shorter PFSMedian PFS: 1.6 vs 5.4 mo(HR 2.04, 95% CI 1.49-2.78)
Novello et al. 2018 (ALUR) 	2015-2018 	Phase 3 (C)	Alectinib 	Shorter PFS1Median PFS: 1.4 vs 10.9 mo(HR 5.00, 95% CI 3.03-8.33)
1Reported efficacy for ALUR is based on the 2022 update.
====Biomarker eligibility criteria====
*Biomarker: ALK Fusion Gene Rearrangement
*Diagnostics: FISH or IHC
====Chemotherapy====
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
====Supportive therapy====
*(per Ardizzoni et al. 2012):
*Dexamethasone (Decadron) 4 mg or equivalent corticosteroid PO twice per day on the day before, the day of, and day after each dose of pemetrexed
*Folic acid (Folate) 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of pemetrexed, to be taken throughout pemetrexed therapy
**JMEI used Folic acid (Folate) 1 mg PO once per day
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of pemetrexed, to be given throughout pemetrexed therapy
21-day cycles
===References===
# ASCEND-5: Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886. Epub 2017 Jun 9. link to original articledosing details in manuscript have been reviewed by our editorsEuroPMC NCT01828112
# ALUR: Novello S, Mazières J, Oh IJ, de Castro J, Migliorino MR, Helland Å, Dziadziuszko R, Griesinger F, Kotb A, Zeaiter A, Cardona A, Balas B, Johannsdottir HK, Das-Gupta A, Wolf J. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018 Jun 1;29(6):1409-1416. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02604342
##Update: Wolf J, Helland Å, Oh IJ, Migliorino MR, Dziadziuszko R, Wrona A, de Castro J, Mazieres J, Griesinger F, Chlistalla M, Cardona A, Ruf T, Trunzer K, Smoljanovic V, Novello S. Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer. ESMO Open. 2022 Feb;7(1):100333. Epub 2022 Jan 15. link to original article link to PMC article EuroPMC
Category:Non-small cell lung cancer regimens
Category:Historical regimens
Category:Biomarker-specific pages
Category:Lung cancers