Malignant pleural mesothelioma

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Last updated on 2024-09-06:19 regimens on this page
33 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.
==ASCO==
*2018: Kindler et al. Treatment of malignant pleural mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline link to PMC article EuroPMC
==ESMO==
*2021: Popat et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2015: Baas et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. EuroPMC
**2010: Stahel et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Stahel et al. Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2008: Stahel et al. Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN Guidelines - Mesothelioma: Pleural
**2024: Stevenson et al. NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024 EuroPMC
**2023: Ettinger et al. Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology EuroPMC
**2016: Ettinger et al. NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016 EuroPMC
**2012: Ettinger et al. Malignant pleural mesothelioma. EuroPMC
==SITC==
*2022: Govindan et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma link to PMC article EuroPMC
=Advanced or metastatic disease, first-line therapy=
==Carboplatin & Pemetrexed==
===Regimen variant #1, AUC 5/500 x 6===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Castagneto et al. 2007 	2003-07 to 2005-03 	Phase 2 	 	
Baas et al. 2021 (CheckMate 743) 	2016-2018 	Phase 3 (C)	Ipilimumab & Nivolumab 	Shorter OS1Median OS: 14.1 vs 18.1 mo(HR 1.37, 95% CI 1.15-1.64)
Chu et al. 2023 (IND227) 	2017-01-31 to 2020-09-04	Phase 3 (C)	1a. Carboplatin, Pemetrexed, Pembrolizumab1b. Cisplatin, Pemetrexed, Pembrolizumab	Seems to have shorter OSMedian OS: 16.1 vs 17.3 mo(HR 1.27, 95% CI 1.02-1.56)
Szlosarek et al. 2024 (ATOMIC-Meso)	2017-08-01 to 2021-08-15	Phase 3 (C)	1a. Carboplatin, Pegargimanse, Pemetrexed1b. Cisplatin, Pegargimanse, Pemetrexed 	Shorter OS (primary endpoint)Median OS: 7.7 vs 9.3 mo(HR 1.41, 95% CI 1.08-1.82)
1Reported efficacy for CheckMate 743 is based on the 2022 update.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second, 30 minutes after pemetrexed
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
====Supportive therapy====
*(varies depending on reference):
*Folic acid 350 to 600 mcg PO once per day, starting at least 1 week prior to pemetrexed, to continue throughout therapy
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week prior to pemetrexed, then 1000 mcg IM once every 9 weeks
*Dexamethasone (Decadron) by one of the following:
**4 mg PO twice per day the day before, the day of, and day after pemetrexed
**8 mg IM once the day before, the day of, and day after pemetrexed
*No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after pemetrexed 
21-day cycle for 6 cycles
===Regimen variant #2, AUC 5/500 x 9===
Study 	Dates of enrollment	Evidence
Castagneto et al. 2007	2003-07 to 2005-03 	Phase 2
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second, 30 minutes after pemetrexed
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
====Supportive therapy====
*(varies depending on reference):
*Folic acid 350 to 600 mcg PO once per day, starting at least 1 week prior to pemetrexed, to continue throughout therapy
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week prior to pemetrexed, then 1000 mcg IM once every 9 weeks
*Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
**Alternatively, Dexamethasone (Decadron) may be given 8 mg IM the day before, the day of, and day after pemetrexed
*No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after pemetrexed 
21-day cycle for up to 9 cycles
===Regimen variant #3, AUC 5/500, indefinite===
Study 	Dates of enrollment	Evidence
Ceresoli et al. 2006	2002-11 to 2005-03 	Phase 2
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second, 30 minutes after pemetrexed
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
====Supportive therapy====
*(varies depending on reference):
*Folic acid 350 to 600 mcg PO once per day, starting at least 1 week prior to pemetrexed, to continue throughout therapy
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week prior to pemetrexed, then 1000 mcg IM once every 9 weeks
*Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
**Alternatively, Dexamethasone (Decadron) may be given 8 mg IM the day before, the day of, and day after pemetrexed
*No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after pemetrexed 
21-day cycles
===Regimen variant #4, AUC 6/500 x 6===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Chu et al. 2023 (IND227)	2017-01-31 to 2020-09-04	Phase 3 (C)	1a. Carboplatin, Pemetrexed, Pembrolizumab1b. Cisplatin, Pemetrexed, Pembrolizumab	Seems to have shorter OSMedian OS: 16.1 vs 17.3 mo(HR 1.27, 95% CI 1.02-1.56)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
====Supportive therapy====
*(varies depending on reference):
*Folic acid 350 to 600 mcg PO once per day, starting at least 1 week prior to pemetrexed, to continue throughout therapy
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week prior to pemetrexed, then 1000 mcg IM once every 9 weeks
*Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
**Alternatively, Dexamethasone (Decadron) may be given 8 mg IM the day before, the day of, and day after pemetrexed
*No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after pemetrexed 
21-day cycle for 6 cycles
===References===
# Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, Ceribelli A, Bearz A, Morenghi E, Cavina R, Marangolo M, Parra HJ, Santoro A. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006 Mar 20;24(9):1443-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Castagneto B, Botta M, Aitini E, Spigno F, Degiovanni D, Alabiso O, Serra M, Muzio A, Carbone R, Buosi R, Galbusera V, Piccolini E, Giaretto L, Rebella L, Mencoboni M. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann Oncol. 2008 Feb;19(2):370-3. Epub 2007 Dec 20. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# CheckMate 743: Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Jahan T, Antonia S, Oulkhouir Y, Bautista Y, Cornelissen R, Greillier L, Grossi F, Kowalski D, Rodríguez-Cid J, Aanur P, Oukessou A, Baudelet C, Zalcman G. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. Epub 2021 Jan 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02899299
##Update: Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, Talbot T, Monnet I, Hiret S, Baas P, Nowak AK, Fujimoto N, Tsao AS, Mansfield AS, Popat S, Zhang X, Hu N, Balli D, Spires T, Zalcman G. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022 May;33(5):488-499. Epub 2022 Feb 3. link to original article EuroPMC
#IND227: Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. Epub 2023 Nov 3. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02784171
#ATOMIC-Meso: Szlosarek PW, Creelan BC, Sarkodie T, Nolan L, Taylor P, Olevsky O, Grosso F, Cortinovis D, Chitnis M, Roy A, Gilligan D, Kindler H, Papadatos-Pastos D, Ceresoli GL, Mansfield AS, Tsao A, O'Byrne KJ, Nowak AK, Steele J, Sheaff M, Shiu CF, Kuo CL, Johnston A, Bomalaski J, Zauderer MG, Fennell DA; ATOMIC-Meso Study Group. Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial. JAMA Oncol. 2024 Apr 1;10(4):475-483. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT02709512
==Carboplatin, Pemetrexed, Bevacizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Awaiting publication (BEAT-meso)	2019-ongoing 	Phase 3 (C)	ABCP 	TBD if different primary endpoint of OS
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4 up to 6: AUC 5 IV once on day 1
*Pemetrexed (Alimta) as follows:
**Cycles 1 to 4 up to 6: 500 mg/m2 IV once on day 1
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
===References===
#BEAT-meso: NCT03762018
==Carboplatin, Pemetrexed, Pembrolizumab==
===Regimen variant #1, AUC 5===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Chu et al. 2023 (IND227)	2017-01-31 to 2020-09-04	Phase 3 (E-esc)	1a. Carboplatin & Pemetrexed1b. Cisplatin & Pemetrexed	Seems to have longer OS (primary endpoint)Median OS: 17.3 vs 16.1 mo(HR 0.79, 95% CI 0.64-0.98)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 5 IV once on day 1
*Pemetrexed (Alimta) as follows:
**Cycles 1 to 6: 500 mg/m2 IV once on day 1
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===Regimen variant #2, AUC 6===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Chu et al. 2023 (IND227)	2017-01-31 to 2020-09-04	Phase 3 (E-esc)	1a. Carboplatin & Pemetrexed1b. Cisplatin & Pemetrexed	Seems to have longer OS (primary endpoint)Median OS: 17.3 vs 16.1 mo(HR 0.79, 95% CI 0.64-0.98)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 6 IV once on day 1
*Pemetrexed (Alimta) as follows:
**Cycles 1 to 6: 500 mg/m2 IV once on day 1
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===References===
#IND227: Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. Epub 2023 Nov 3. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02784171
==Cisplatin monotherapy==
===Regimen variant #1, 75 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Vogelzang et al. 2003 (EMPHACIS)	1999-2001 	Phase 3 (C)	Cisplatin & Pemetrexed	Seems to have shorter OSMedian OS: 9.3 vs 12.1 mo(HR 1.30)
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV over 2 hours once on day 1
21-day cycles
===Regimen variant #2, 80 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
van Meerbeeck et al. 2005 (EORTC 08983)	2000-2003 	Phase 3 (C)	Cisplatin & Raltitrexed	Seems to have shorter OSMedian OS: 8.8 vs 11.4 mo(HR 1.32, 95% CI 1.00-1.72)
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV over 1 to 2 hours once on day 1
21-day cycles
===References===
# EMPHACIS: Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005636
## Update: Manegold C, Symanowski J, Gatzemeier U, Reck M, von Pawel J, Kortsik C, Nackaerts K, Lianes P, Vogelzang NJ. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Ann Oncol. 2005 Jun;16(6):923-7. Epub 2005 Apr 11. link to original article EuroPMC
# EORTC 08983: van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G; EORTC Lung Cancer Group; National Cancer Institute of Canada Clinical Trials Group. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005 Oct 1;23(28):6881-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00004920
==Cisplatin & Gemcitabine (GC)==
===Regimen variant #1, 100/1000===
Study 	Dates of enrollment	Evidence
Nowak et al. 2002	Not reported 	Phase 2
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 1, given first
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, given second
====Supportive therapy====
*Minimum of 3 liters of IV hydration for [cisplatin, with magnesium supplementation
*5-HT3 antagonists & Dexamethasone (Decadron) IV once per day on days 1, 8, 15, prior to chemotherapy
*5-HT3 antagonists, Dexamethasone (Decadron), and/or phenothiazines for antiemesis PO or by rectal suppository for 3 to 5 days after cisplatin
28-day cycle for up to 6 cycles
===Regimen variant #2, 80/1250===
Study 	Dates of enrollment	Evidence
van Haarst et al. 2002	1999-04 to 1999-12 	Phase 2
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV over 3 hours once on day 1, given second
*Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
====Supportive therapy====
*Minimum of 2 liters of IV hydration for cisplatin
*5-HT3 antagonists prior to cisplatin
*corticosteroids prior to cisplatin
21-day cycle for up to 6 cycles
===References===
# van Haarst JM, Baas P, Manegold Ch, Schouwink JH, Burgers JA, de Bruin HG, Mooi WJ, van Klaveren RJ, de Jonge MJ, van Meerbeeck JP. Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma. Br J Cancer. 2002 Feb 1;86(3):342-5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC content property of HemOnc.org 
# Nowak AK, Byrne MJ, Williamson R, Ryan G, Segal A, Fielding D, Mitchell P, Musk AW, Robinson BW. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma. Br J Cancer. 2002 Aug 27;87(5):491-6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==Cisplatin & Pemetrexed==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Vogelzang et al. 2003 (EMPHACIS) 	1999-2001 	Phase 3 (E-RT-esc)	Cisplatin 	Seems to have longer OS (primary endpoint)Median OS: 12.1 vs 9.3 mo(HR 0.77)
Zalcman et al. 2016 (MAPS) 	2008-2014 	Phase 3 (C) 	PCB 	Shorter OSMedian OS: 16.1 vs 18.8 mo(HR 1.30, 95% CI 1.05-1.61)
Grosso et al. 2017 (LUME-Meso) 	2013-09 to 2014-12 	Phase 2/3 (C) 	Cisplatin, Nintedanib, Pemetrexed 	Did not meet primary endpoint of PFS1
Lim et al. 2024 (MARS 2) 	2015-06-19 to 2021-01-21	Phase 3 (C) 	Chemotherapy & Extended pleurectomy decortication 	Longer OS (primary endpoint)Median OS: 24.8 vs 19.3 mo(RMST24: -1.9 mo, 95% CI -3.4 to -0.3 mo)
Baas et al. 2021 (CheckMate 743) 	2016-2018 	Phase 3 (C) 	Ipilimumab & Nivolumab 	Shorter OS2Median OS: 14.1 vs 18.1 mo(HR 1.37, 95% CI 1.15-1.64)
Chu et al. 2023 (IND227) 	2017-01-31 to 2020-09-04	Phase 3 (C) 	1a. Carboplatin, Pemetrexed, Pembrolizumab1b. Cisplatin, Pemetrexed, Pembrolizumab	Seems to have shorter OSMedian OS: 16.1 vs 17.3 mo(HR 1.27, 95% CI 1.02-1.56)
Szlosarek et al. 2024 (ATOMIC-Meso)	2017-08-01 to 2021-08-15	Phase 3 (C) 	1a. Carboplatin, Pegargimanse, Pemetrexed1b. Cisplatin, Pegargimanse, Pemetrexed 	Shorter OS (primary endpoint)Median OS: 7.7 vs 9.3 mo(HR 1.41, 95% CI 1.08-1.82)
Awaiting publication (DREAM3R) 	2021-ongoing 	Phase 3 (C) 	1a. Carboplatin, Pemetrexed, Durvalumab1b. Cisplatin, Pemetrexed, Durvalumab 	TBD if different primary endpoint of OS
1Reported efficacy for LUME-Meso is based on the 2019 update.
2Reported efficacy for CheckMate 743 is based on the 2022 update.
Note: EMPHACIS (aka JMCH) did not specify the total number of cycles and some patients did receive more than 6 cycles. MARS 2 did not specify the type or dosing of chemotherapy; it is included here since this was a common first-line treatment regimen at the time the trial was conducted.
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV over 2 hours once on day 1, given second, 30 minutes after pemetrexed
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
====Supportive therapy====
*Folic acid 350 to 1000 mcg PO once per day, starting 1 to 3 weeks prior to pemetrexed, to continue throughout therapy
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 3 weeks prior to pemetrexed, then 1000 mcg IM once every 9 weeks
*Dexamethasone (Decadron) (dose not specified by reference) the day before, the day of, and day after pemetrexed
21-day cycle for up to 6 cycles (see note)
===References===
# EMPHACIS: Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005636
## Update: Manegold C, Symanowski J, Gatzemeier U, Reck M, von Pawel J, Kortsik C, Nackaerts K, Lianes P, Vogelzang NJ. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Ann Oncol. 2005 Jun;16(6):923-7. Epub 2005 Apr 11. link to original article EuroPMC
# MAPS: Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, Rivière F, Janicot H, Gervais R, Locher C, Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Parienti JJ, Scherpereel A; IFCT. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2;387(10026):1405-14. Epub 2015 Dec 21. Erratum in: Lancet. 2016 Apr 2;387(10026):e24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00651456
##HRQoL analysis: Eberst G, Anota A, Scherpereel A, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Léna H, Rivière F, Monnet I, Gounant V, Janicot H, Gervais R, Locher C, Charton E, Morin F, Zalcman G, Westeel V; French Cooperative Thoracic Intergroup (IFCT). Health-Related Quality of Life Impact from Adding Bevacizumab to Cisplatin-Pemetrexed in Malignant Pleural Mesothelioma in the MAPS IFCT-GFPC-0701 Phase III Trial. Clin Cancer Res. 2019 Oct;25(19):5759-5765. link to original article link to EuroPMC
# LUME-Meso: Grosso F, Steele N, Novello S, Nowak AK, Popat S, Greillier L, John T, Leighl NB, Reck M, Taylor P, Planchard D, Sørensen JB, Socinski MA, von Wangenheim U, Loembé AB, Barrueco J, Morsli N, Scagliotti G. Nintedanib plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma: Phase II results from the randomized, placebo-controlled LUME-Meso trial. J Clin Oncol. 2017 Nov 1;35(31):3591-3600. Epub 2017 Sep 11. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01907100
## Update: Scagliotti GV, Gaafar R, Nowak AK, Nakano T, van Meerbeeck J, Popat S, Vogelzang NJ, Grosso F, Aboelhassan R, Jakopovic M, Ceresoli GL, Taylor P, Orlandi F, Fennell DA, Novello S, Scherpereel A, Kuribayashi K, Cedres S, Sørensen JB, Pavlakis N, Reck M, Velema D, von Wangenheim U, Kim M, Barrueco J, Tsao AS. Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2019 Jul;7(7):569-580. Epub 2019 May 15. link to original article EuroPMC
# CheckMate 743: Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Jahan T, Antonia S, Oulkhouir Y, Bautista Y, Cornelissen R, Greillier L, Grossi F, Kowalski D, Rodríguez-Cid J, Aanur P, Oukessou A, Baudelet C, Zalcman G. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. Epub 2021 Jan 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02899299
##Update: Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, Talbot T, Monnet I, Hiret S, Baas P, Nowak AK, Fujimoto N, Tsao AS, Mansfield AS, Popat S, Zhang X, Hu N, Balli D, Spires T, Zalcman G. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022 May;33(5):488-499. Epub 2022 Feb 3. link to original article EuroPMC
#IND227: Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. Epub 2023 Nov 3. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02784171
#ATOMIC-Meso: Szlosarek PW, Creelan BC, Sarkodie T, Nolan L, Taylor P, Olevsky O, Grosso F, Cortinovis D, Chitnis M, Roy A, Gilligan D, Kindler H, Papadatos-Pastos D, Ceresoli GL, Mansfield AS, Tsao A, O'Byrne KJ, Nowak AK, Steele J, Sheaff M, Shiu CF, Kuo CL, Johnston A, Bomalaski J, Zauderer MG, Fennell DA; ATOMIC-Meso Study Group. Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial. JAMA Oncol. 2024 Apr 1;10(4):475-483. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT02709512
#MARS 2: Lim E, Waller D, Lau K, Steele J, Pope A, Ali C, Bilancia R, Keni M, Popat S, O'Brien M, Tokaca N, Maskell N, Stadon L, Fennell D, Nelson L, Edwards J, Tenconi S, Socci L, Rintoul RC, Wood K, Stone A, Muthukumar D, Ingle C, Taylor P, Cove-Smith L, Califano R, Summers Y, Tasigiannopoulos Z, Bille A, Shah R, Fuller E, Macnair A, Shamash J, Mansy T, Milton R, Koh P, Ionescu AA, Treece S, Roy A, Middleton G, Kirk A, Harris RA, Ashton K, Warnes B, Bridgeman E, Joyce K, Mills N, Elliott D, Farrar N, Stokes E, Hughes V, Nicholson AG, Rogers CA; MARS 2 Investigators. Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial. Lancet Respir Med. 2024 Jun;12(6):457-466. Epub 2024 May 10. link to original article link to PMC article does not contain dosing details EuroPMC NCT02040272
#DREAM3R: NCT04334759
==Cisplatin & Raltitrexed==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
van Meerbeeck et al. 2005 (EORTC 08983)	2000-2003 	Phase 3 (E-esc)	Cisplatin 	Seems to have longer OS (primary endpoint)Median OS: 11.4 vs 8.8 mo(HR 0.76, 95% CI 0.58-1.00)
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV over 1 to 2 hours once on day 1, given second
*Raltitrexed (Tomudex) 3 mg/m2 IV over 15 minutes once on day 1, given first
21-day cycles
===References===
# EORTC 08983: van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G; EORTC Lung Cancer Group; National Cancer Institute of Canada Clinical Trials Group. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005 Oct 1;23(28):6881-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00004920
==Cisplatin, Pemetrexed, Bevacizumab==
PCB: Pemetrexed, Cisplatin, Bevacizumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zalcman et al. 2016 (MAPS)	2008-2014 	Phase 3 (E-esc)	PC 	Longer OS (primary endpoint)Median OS: 18.8 vs 16.1 mo(HR 0.77, 95% CI 0.62-0.95)
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 6 cycles
===References===
# MAPS: Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, Rivière F, Janicot H, Gervais R, Locher C, Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Parienti JJ, Scherpereel A; IFCT. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2;387(10026):1405-14. Epub 2015 Dec 21. Erratum in: Lancet. 2016 Apr 2;387(10026):e24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00651456
##HRQoL analysis: Eberst G, Anota A, Scherpereel A, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Léna H, Rivière F, Monnet I, Gounant V, Janicot H, Gervais R, Locher C, Charton E, Morin F, Zalcman G, Westeel V; French Cooperative Thoracic Intergroup (IFCT). Health-Related Quality of Life Impact from Adding Bevacizumab to Cisplatin-Pemetrexed in Malignant Pleural Mesothelioma in the MAPS IFCT-GFPC-0701 Phase III Trial. Clin Cancer Res. 2019 Oct;25(19):5759-5765. link to original article link to EuroPMC
==Cisplatin, Pemetrexed, Pembrolizumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Chu et al. 2023 (IND227)	2017-01-31 to 2020-09-04	Phase 3 (E-esc)	1a. Carboplatin & Pemetrexed1b. Cisplatin & Pemetrexed	Seems to have longer OS (primary endpoint)Median OS: 17.3 vs 16.1 mo(HR 0.79, 95% CI 0.64-0.98)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 6: 75 mg/m2 IV once on day 1
*Pemetrexed (Alimta) as follows:
**Cycles 1 to 6: 500 mg/m2 IV once on day 1
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===References===
#IND227: Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. Epub 2023 Nov 3. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02784171
==Cisplatin, Pemetrexed, TTFields==
===Regimen===
Study 	Dates of enrollment	Evidence
Ceresoli et al. 2019 (STELLAR)	2015-2017 	Phase 2
====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 up to 6 cycles
====Tumor treating fields====
*NovoTTF-100A system (Optune)
===References===
# STELLAR: Ceresoli GL, Aerts JG, Dziadziuszko R, Ramlau R, Cedres S, van Meerbeeck JP, Mencoboni M, Planchard D, Chella A, Crinò L, Krzakowski M, Rüssel J, Maconi A, Gianoncelli L, Grosso F. Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1702-1709. Epub 2019 Oct 15. link to original article EuroPMC NCT02397928
==Ipilimumab & Nivolumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Baas et al. 2021 (CheckMate 743)	2016-2018 	Phase 3 (E-RT-switch-ooc)	1a. Carboplatin & Pemetrexed1b. Cisplatin & Pemetrexed	Longer OS1 (primary endpoint)Median OS: 18.1 vs 14.1 mo (HR 0.73, 95% CI 0.61-0.87)
1Reported efficacy is based on the 2022 update.
====Immunotherapy====
*Ipilimumab (Yervoy) 1 mg/kg IV once on day 1, given second
*Nivolumab (Opdivo) 3 mg/kg IV once per day on days 1, 15, 29, given first
42-day cycle for up to 18 cycles (2 years)
===References===
# CheckMate 743: Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Jahan T, Antonia S, Oulkhouir Y, Bautista Y, Cornelissen R, Greillier L, Grossi F, Kowalski D, Rodríguez-Cid J, Aanur P, Oukessou A, Baudelet C, Zalcman G. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. Epub 2021 Jan 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02899299
##Update: Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, Talbot T, Monnet I, Hiret S, Baas P, Nowak AK, Fujimoto N, Tsao AS, Mansfield AS, Popat S, Zhang X, Hu N, Balli D, Spires T, Zalcman G. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022 May;33(5):488-499. Epub 2022 Feb 3. link to original article EuroPMC
==Pemetrexed monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Taylor et al. 2008	Not reported 	Phase 2
====Chemotherapy====
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
====Supportive therapy====
*Folic acid 350 to 600 mcg PO once per day, starting 1 to 2 weeks before pemetrexed, to continue throughout therapy and at least 3 weeks after the last dose of pemetrexed
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 2 weeks prior to pemetrexed, then 1000 mcg IM once every 9 weeks
*Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
21-day cycles
===References===
# Taylor P, Castagneto B, Dark G, Marangolo M, Scagliotti GV, van Klaveren RJ, Labianca R, Serke M, Schuette W, van Meerbeeck JP, Heigener D, Liu Y, Adachi S, Blatter J, von Pawel J. Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. J Thorac Oncol. 2008 Jul;3(7):764-71. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Vinorelbine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Muers et al. 2008 (MS01)	2001-2006 	Phase 3 (E-esc)	1. Best supportive care	Might have longer OS (primary endpoint)Median OS: 9.5 vs 7.6 mo(HR 0.80, 95% CI 0.63-1.02)
Muers et al. 2008 (MS01)	2001-2006 	Phase 3 (E-esc)	2. MVP 	Not directly compared
Note: Some guidelines list the dosage as 25 to 30 mg/m2. No primary reference could be found for the 25 mg/m2 dosage. Note also that it is not clear from the reference whether 11 or 12 doses were given.
====Chemotherapy====
*Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
7-week cycle for 2 cycles
===References===
# MS01: Muers MF, Stephens RJ, Fisher P, Darlison L, Higgs CM, Lowry E, Nicholson AG, O'Brien M, Peake M, Rudd R, Snee M, Steele J, Girling DJ, Nankivell M, Pugh C, Parmar MK; MS01 Trial Management Group. Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet. 2008 May 17;371(9625):1685-94. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00075699
=Advanced or metastatic disease, subsequent lines of therapy=
==Doxorubicin monotherapy==
===Regimen variant #1, 60 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gregorc et al. 2018 (NGR015)	2010-2013 	Phase 3 (C)	Investigator's choice of:1a. Doxorubicin & NGR-hTNF1b. Gemcitabine & NGR-hTNF1c. Vinorelbine & NGR-hTNF	Did not meet primary endpoint of OSMedian OS: 8 vs 8.5 mo(HR 1.06, 95% CI 0.85-1.33)
Note: To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
====Prior treatment criteria====
*NGR015: One prior pemetrexed-containing regimen
====Chemotherapy====
*Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
===Regimen variant #2, 75 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gregorc et al. 2018 (NGR015)	2010-2013 	Phase 3 (C)	Investigator's choice of:1a. Doxorubicin & NGR-hTNF1b. Gemcitabine & NGR-hTNF1c. Vinorelbine & NGR-hTNF	Did not meet primary endpoint of OSMedian OS: 8 vs 8.5 mo(HR 1.06, 95% CI 0.85-1.33)
Note: To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
====Prior treatment criteria====
*NGR015: One prior pemetrexed-containing regimen
====Chemotherapy====
*Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
===References===
# NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01098266
==Gemcitabine monotherapy==
===Regimen variant #1, 1000 mg/m2, 2 out of 3 weeks===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gregorc et al. 2018 (NGR015) 	2010-2013 	Phase 3 (C)	Investigator's choice of:1a. Doxorubicin & NGR-hTNF1b. Gemcitabine & NGR-hTNF1c. Vinorelbine & NGR-hTNF	Did not meet primary endpoint of OSMedian OS: 8 vs 8.5 mo(HR 1.06, 95% CI 0.85-1.33)
Popat et al. 2020 (PROMISE-meso)	2017-09 to 2018-08 	Phase 3 (C)	Pembrolizumab 	Did not meet primary endpoint of PFSMedian PFS: 3.4 vs 2.5 mo(HR 0.94, 95% CI 0.65-1.37)
Note: To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
====Prior treatment criteria====
*NGR015: One prior pemetrexed-containing regimen
*PROMISE-meso: Failure of platinum-based chemotherapy
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
===Regimen variant #2, 1000 mg/m2, 3 out of 4 weeks===
Study 	Dates of enrollment	Evidence
Zauderer et al. 2014meso	2003-2010 	Retrospective, fewer than 20 pts
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===Regimen variant #3, 1250 mg/m2, 2 out of 3 weeks===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gregorc et al. 2018 (NGR015)	2010-2013 	Phase 3 (C)	Investigator's choice of:1a. Doxorubicin & NGR-hTNF1b. Gemcitabine & NGR-hTNF1c. Vinorelbine & NGR-hTNF	Did not meet primary endpoint of OSMedian OS: 8 vs 8.5 mo(HR 1.06, 95% CI 0.85-1.33)
Note: To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
====Prior treatment criteria====
*NGR015: One prior pemetrexed-containing regimen
====Chemotherapy====
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
===References===
# Retrospective: Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer. 2014 Jun;84(3):271-4. Epub 2014 Mar 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
# NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01098266
# PROMISE-meso: Popat S, Curioni-Fontecedro A, Dafni U, Shah R, O'Brien M, Pope A, Fisher P, Spicer J, Roy A, Gilligan D, Gautschi O, Nadal E, Janthur WD, López Castro R, García Campelo R, Rusakiewicz S, Letovanec I, Polydoropoulou V, Roschitzki-Voser H, Ruepp B, Gasca-Ruchti A, Peters S, Stahel RA. A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Ann Oncol. 2020 Dec;31(12):1734-1745. Epub 2020 Sep 22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02991482
==Gemcitabine & Vinorelbine==
===Regimen===
Study 	Dates of enrollment	Evidence
Zauderer et al. 2014meso	2003-2010 	Retrospective, fewer than 20 pts
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
*Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycles
===References===
# Retrospective: Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer. 2014 Jun;84(3):271-4. Epub 2014 Mar 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==Nivolumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Fennell et al. 2021 (CONFIRMmeso)	2017-2020 	Phase 3 (E-esc)	Placebo 	Longer OS (co-primary endpoint)Median OS: 10.2 vs 6.9 mo(HR 0.69, 95% CI 0.52-0.91)
Note: this trial should not be confused with the one by the same name in breast cancer.
====Prior treatment criteria====
*Failure of first-line platinum-based chemotherapy
====Immunotherapy====
*Nivolumab (Opdivo) 240 mg IV over 30 minutes once on day 1
14-day cycle for up to 26 cycles (1 year)
===References===
# CONFIRMmeso: Fennell DA, Ewings S, Ottensmeier C, Califano R, Hanna GG, Hill K, Danson S, Steele N, Nye M, Johnson L, Lord J, Middleton C, Szlosarek P, Chan S, Gaba A, Darlison L, Wells-Jordan P, Richards C, Poile C, Lester JF, Griffiths G; CONFIRM trial investigators. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol. 2021 Nov;22(11):1530-1540. Epub 2021 Oct 14. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT03063450
==Pemetrexed monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Jassem et al. 2008 (JMEW)	2001-2004 	Phase 3 (E-esc)	Best supportive care	Did not meet primary endpoint of OSMedian OS: 9.7 vs 8.4 mo
====Prior treatment criteria====
*One prior systemic chemotherapy regimen, not including pemetrexed
====Chemotherapy====
*Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
====Supportive therapy====
*Folic acid 350 to 1000 mcg PO once per day, starting 1 to 2 weeks prior to pemetrexed, to continue throughout therapy and at least 3 weeks after the last dose of pemetrexed
*Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 2 weeks prior to pemetrexed, then 1000 mcg IM once every 9 weeks
*Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
21-day cycle for 8 or more cycles
===References===
# JMEW: Jassem J, Ramlau R, Santoro A, Schuette W, Chemaissani A, Hong S, Blatter J, Adachi S, Hanauske A, Manegold C. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol. 2008 Apr 1;26(10):1698-704. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00190762
==Vinorelbine monotherapy==
===Regimen variant #1, 25 mg/m2 IV, weekly===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gregorc et al. 2018 (NGR015)	2010-2013 	Phase 3 (C)	Investigator's choice of:1a. Doxorubicin & NGR-hTNF1b. Gemcitabine & NGR-hTNF1c. Vinorelbine & NGR-hTNF	Did not meet primary endpoint of OSMedian OS: 8 vs 8.5 mo(HR 1.06, 95% CI 0.85-1.33)
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Prior treatment criteria====
*NGR015: One prior pemetrexed-containing regimen
====Chemotherapy====
*Vinorelbine (Navelbine) 25 mg/m2 IV once on day 1
7-day cycle for 12 cycles
===Regimen variant #2, 30 mg/m2 IV, 2 weeks out of 3===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Popat et al. 2020 (PROMISE-meso)	2017-09 to 2018-08 	Phase 3 (C)	Pembrolizumab	Did not meet primary endpoint of PFSMedian PFS: 3.4 vs 2.5 mo(HR 0.94, 95% CI 0.65-1.37)
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Prior treatment criteria====
*PROMISE-meso: Failure of platinum-based chemotherapy
====Chemotherapy====
*Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycles
===Regimen variant #3, 30 mg/m2 IV, weekly===
Study 	Dates of enrollment	Evidence
Stebbing et al. 2008	Not reported 	Phase 2
====Chemotherapy====
*Vinorelbine (Navelbine) 30 mg/m2 (maximum dose of 60 mg) IV over 5 minutes once on day 1
7-day cycles
===Regimen variant #4, 60 mg/m2 PO, 2 weeks out of 3===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Popat et al. 2020 (PROMISE-meso)	2017-09 to 2018-08 	Phase 3 (C)	Pembrolizumab	Did not meet primary endpoint of PFSMedian PFS: 3.4 vs 2.5 mo(HR 0.94, 95% CI 0.65-1.37)
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Prior treatment criteria====
*PROMISE-meso: Failure of platinum-based chemotherapy
====Chemotherapy====
*Vinorelbine (Navelbine) 60 mg/m2 PO once per day on days 1 & 8
21-day cycles
===Regimen variant #5, 60 mg/m2 PO, weekly===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gregorc et al. 2018 (NGR015)	2010-2013 	Phase 3 (C)	Investigator's choice of:1a. Doxorubicin & NGR-hTNF1b. Gemcitabine & NGR-hTNF1c. Vinorelbine & NGR-hTNF	Did not meet primary endpoint of OSMedian OS: 8 vs 8.5 mo(HR 1.06, 95% CI 0.85-1.33)
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Prior treatment criteria====
*NGR015: One prior pemetrexed-containing regimen
====Chemotherapy====
*Vinorelbine (Navelbine) 60 mg/m2 PO once on day 1
7-day cycle for 12 cycles
===Regimen variant #6, 80 mg/m2 PO, 2 weeks out of 3===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Popat et al. 2020 (PROMISE-meso)	2017-09 to 2018-08 	Phase 3 (C)	Pembrolizumab	Did not meet primary endpoint of PFSMedian PFS: 3.4 vs 2.5 mo(HR 0.94, 95% CI 0.65-1.37)
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Prior treatment criteria====
*PROMISE-meso: Failure of platinum-based chemotherapy
====Chemotherapy====
*Vinorelbine (Navelbine) 80 mg/m2 PO once per day on days 1 & 8
21-day cycles
===References===
# Stebbing J, Powles T, McPherson K, Shamash J, Wells P, Sheaff MT, Slater S, Rudd RM, Fennell D, Steele JP. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer. 2009 Jan;63(1):94-7. Epub 2008 May 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01098266
# PROMISE-meso: Popat S, Curioni-Fontecedro A, Dafni U, Shah R, O'Brien M, Pope A, Fisher P, Spicer J, Roy A, Gilligan D, Gautschi O, Nadal E, Janthur WD, López Castro R, García Campelo R, Rusakiewicz S, Letovanec I, Polydoropoulou V, Roschitzki-Voser H, Ruepp B, Gasca-Ruchti A, Peters S, Stahel RA. A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Ann Oncol. 2020 Dec;31(12):1734-1745. Epub 2020 Sep 22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02991482
Category:Malignant pleural mesothelioma regimens
Category:Disease-specific pages
Category:Thoracic cancers
Category:Mesotheliomas