Malignant pleural mesothelioma - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main MPM page for regimens that include active anticancer treatment.
=Advanced or metastatic disease, first-line therapy=
==Best supportive care==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Muers et al. 2008 (MS01)	2001-2006 	Phase 3 (C)	1. MVP 	Did not meet primary endpoint of OS
Muers et al. 2008 (MS01)	2001-2006 	Phase 3 (C)	2. Vinorelbine	Might have shorter OS
No antineoplastic treatment; used as a comparator arm and here for reference purposes only.
===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 link to PMC article EuroPMC NCT00075699
=Maintenance after first-line therapy=
==Best supportive care==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Buikhuisen et al. 2013 (NVALT 5)	2004-2009 	Phase 3 (C)	Thalidomide	Did not meet primary endpoint of TTP
Aerts et al. 2024 (DENIM) 	2018-06-21 to 2021-06-10	Phase 3 (C)	MesoPher 	Did not meet primary endpoint of OS
No antineoplastic treatment after first-line therapy.
====Preceding treatment====
*NVALT 5: First-line pemetrexed-containing chemotherapy x 4
*DENIM: First-line Carboplatin & Pemetrexed or Cisplatin & Pemetrexed x 4 to 6
===References===
# NVALT 5: Buikhuisen WA, Burgers JA, Vincent AD, Korse CM, van Klaveren RJ, Schramel FM, Pavlakis N, Nowak AK, Custers FL, Schouwink JH, Gans SJ, Groen HJ, Strankinga WF, Baas P. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study. Lancet Oncol. 2013 May;14(6):543-51. Epub 2013 Apr 12. link to original article EuroPMC ISRCTN13632914
#DENIM: Aerts JG, Belderbos R, Baas P, Scherpereel A, Bezemer K, Enninga I, Meijer R, Willemsen M, Berardi R, Fennell D, Kerstens R, Cornelissen R, van Meerbeeck JP; DENIM team. Dendritic cells loaded with allogeneic tumour cell lysate plus best supportive care versus best supportive care alone in patients with pleural mesothelioma as maintenance therapy after chemotherapy (DENIM): a multicentre, open-label, randomised, phase 2/3 study. Lancet Oncol. 2024 Jul;25(7):865-878. Epub 2024 Jun 4. link to original article EuroPMC NCT03610360
=Advanced or metastatic disease, subsequent lines of therapy=
==Best supportive care==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Jassem et al. 2008 (JMEW) 	2001-2004 	Phase 3 (C) 	Pemetrexed 	Seems to have shorter PFS
Maio et al. 2017 (DETERMINE)	2013-2014 	Randomized Phase 2b (C)	Tremelimumab	Did not meet primary endpoint of OS
No antineoplastic treatment.
===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 EuroPMC NCT00190762
# DETERMINE: Maio M, Scherpereel A, Calabrò L, Aerts J, Cedres Perez S, Bearz A, Nackaerts K, Fennell DA, Kowalski D, Tsao AS, Taylor P, Grosso F, Antonia SJ, Nowak AK, Taboada M, Puglisi M, Stockman PK, Kindler HL. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017 Sep;18(9):1261-1273. Epub 2017 Jul 17. link to original article EuroPMC NCT01843374
==Placebo==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Krug et al. 2015 (VANTAGE-014) 	2005-2011 	Phase 3 (C)	Vorinostat	Did not meet primary endpoint of OSMedian OS: 27.1 vs 30.7 weeks(HR 1.02, 95% CI 0.85-1.20)
Fennell et al. 2021 (CONFIRMmeso)	2017-2020 	Phase 3 (C)	Nivolumab 	Shorter OS (co-primary endpoint)Median OS: 6.9 vs 10.2 mo(HR 1.45, 95% CI 1.10-1.92)
No active antineoplastic treatment. Note that we have renamed CONFIRM to avoid confusion with the trial by the same name in breast cancer.
===References===
# VANTAGE-014: Krug LM, Kindler HL, Calvert H, Manegold C, Tsao AS, Fennell D, Öhman R, Plummer R, Eberhardt WE, Fukuoka K, Gaafar RM, Lafitte JJ, Hillerdal G, Chu Q, Buikhuisen WA, Lubiniecki GM, Sun X, Smith M, Baas P. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2015 Apr;16(4):447-56. Epub 2015 Mar 20. Erratum in: Lancet Oncol. 2015 May;16(5):e199. link to original article EuroPMC NCT00128102
# 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 link to PMC article EuroPMC NCT03063450
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