A Meta-Analysis of First-Line Treatments for Unresectable Pleural Mesothelioma: Indirect Comparisons from Reconstructed Individual Patient Data of Six Randomized Controlled Trials

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2025 Feb 13

PMID 39941870

Authors

Andrea Messori

Sabrina Trippoli

Eugenia Piragine

Sara Veneziano

Vincenzo Calderone

Affiliations

Soon will be listed here.

Abstract

Background: In unresectable pleural mesothelioma, pemetrexed+cisplatin as first line is considered the standard of care, but novel treatments have been recently proposed.

Methods: Our objective was to compare, albeit indirectly, the results of randomized controlled trials on overall survival (OS). The IPDfromKM method was employed for reconstruct individual patient data (IPD) from the graphs of Kaplan-Meier curves. Cox statistics was run to estimate hazard ratios (HRs).

Results: After a literature search on Medline (via PubMed) and Scopus databases, six randomized controlled trials were identified in which five new treatments (nivolumab plus ipilimumab, bevacizumab plus pemetrexed plus cisplatin, chemotherapy plus pembrolizumab, ONCOS-102 plus pemetrexed plus cisplatin/carboplatin and cediranib plus pemetrexed+cisplatin with maintenance with cediranib) were evaluated. In five trials, pemetrexed plus cisplatin was the standard of care given to the control arms. Nivolumab plus ipilimumab, bevacizumab plus pemetrexed plus cisplatin and chemotherapy plus pembrolizumab showed a significantly better OS compared with controls. ONCOS-102 plus pemetrexed plus cisplatin/carboplatin did not significantly improve OS. In contrast, OS worsened with cisplatin alone and with cediranib plus pemetrexed+cisplatin with maintenance with cediranib.

Discussion: Our analysis indicates that, in patients with unresectable pleural mesothelioma, three of the five novel treatments provided a significant survival benefit compared with the standard of care. Further research is needed to confirm the OS benefit found in our analysis with some treatments, whereas cisplatin alone and cediranib plus pemetrexed+cisplatin with maintenance with cediranib do not seem to deserve further research.

References

Santoro A, OBrien M, Stahel R, Nackaerts K, Baas P, Karthaus M . Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program. J Thorac Oncol. 2008; 3(7):756-63. DOI: 10.1097/JTO.0b013e31817c73d6. View

Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D . Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016; 387(10026):1405-1414. DOI: 10.1016/S0140-6736(15)01238-6. View

Nowak A, Lesterhuis W, Kok P, Brown C, Hughes B, Karikios D . Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in. Lancet Oncol. 2020; 21(9):1213-1223. DOI: 10.1016/S1470-2045(20)30462-9. View

Correale P, Pentimalli F, Nardone V, Giordano A, Mutti L . CONFIRM trial: what is the real efficacy of second-line immunotherapy in mesothelioma?. Lancet Oncol. 2022; 23(1):e13. DOI: 10.1016/S1470-2045(21)00702-6. View

Vogelzang N, Rusthoven J, Symanowski J, Denham C, Kaukel E, Ruffie P . Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma. J Clin Oncol. 2023; 41(12):2125-2133. DOI: 10.1200/JCO.22.02542. View

Liu N, Zhou Y, Lee J . IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2021; 21(1):111. PMC: 8168323. DOI: 10.1186/s12874-021-01308-8. View

Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan M . First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022; 33(5):488-499. DOI: 10.1016/j.annonc.2022.01.074. View

Cashman K, Ritz C . Individual participant data (IPD)-level meta-analysis of randomised controlled trials among dark-skinned populations to estimate the dietary requirement for vitamin D. Syst Rev. 2019; 8(1):128. PMC: 6540379. DOI: 10.1186/s13643-019-1032-6. View

Marshall A, Bayes H, Bardgett J, Wedderburn S, Kerr K, Currie G . Survival from malignant mesothelioma: where are we now?. J R Coll Physicians Edinb. 2015; 45(2):123-6. DOI: 10.4997/JRCPE.2015.207. View

10.

Popat S, Baas P, Faivre-Finn C, Girard N, Nicholson A, Nowak A . Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021; 33(2):129-142. DOI: 10.1016/j.annonc.2021.11.005. View

11.

Schumann S, Kocher G, Minervini F . Epidemiology, diagnosis and treatment of the malignant pleural mesothelioma, a narrative review of literature. J Thorac Dis. 2021; 13(4):2510-2523. PMC: 8107529. DOI: 10.21037/jtd-20-2761. View

12.

Ponce S, Cedres S, Ricordel C, Isambert N, Viteri S, Herrera-Juarez M . ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment. J Immunother Cancer. 2023; 11(9). PMC: 10476122. DOI: 10.1136/jitc-2023-007552. View

13.

Wach J, Vychopen M, Guresir A, Guranda A, Nestler U, Guresir E . A Long-Term Comparative Analysis of Endovascular Coiling and Clipping for Ruptured Cerebral Aneurysms: An Individual Patient-Level Meta-Analysis Assessing Rerupture Rates. J Clin Med. 2024; 13(6). PMC: 10970744. DOI: 10.3390/jcm13061778. View

14.

Baas P, Scherpereel A, Nowak A, Fujimoto N, Peters S, Tsao A . First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021; 397(10272):375-386. DOI: 10.1016/S0140-6736(20)32714-8. View

15.

Amin W, Linkov F, Landsittel D, Silverstein J, Bashara W, Gaudioso C . Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort. F1000Res. 2019; 7:1184. PMC: 6198263. DOI: 10.12688/f1000research.15512.3. View

16.

Marchevsky A, Khoor A, Walts A, Nicholson A, Zhi Zhang Y, Roggli V . Localized malignant mesothelioma, an unusual and poorly characterized neoplasm of serosal origin: best current evidence from the literature and the International Mesothelioma Panel. Mod Pathol. 2019; 33(2):281-296. PMC: 10428660. DOI: 10.1038/s41379-019-0352-3. View

17.

Ricciardi S, Cardillo G, Zirafa C, Carleo F, Facciolo F, Fontanini G . Surgery for malignant pleural mesothelioma: an international guidelines review. J Thorac Dis. 2018; 10(Suppl 2):S285-S292. PMC: 5830571. DOI: 10.21037/jtd.2017.10.16. View

18.

Fujimoto E, Kijima T, Kuribayashi K, Negi Y, Kanemura S, Mikami K . First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma. Expert Rev Anticancer Ther. 2017; 17(9):865-872. DOI: 10.1080/14737140.2017.1340157. View

19.

Liberati A, Altman D, Tetzlaff J, Mulrow C, Gotzsche P, Ioannidis J . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009; 151(4):W65-94. DOI: 10.7326/0003-4819-151-4-200908180-00136. View

20.

Rogula B, Lozano-Ortega G, Johnston K . A Method for Reconstructing Individual Patient Data From Kaplan-Meier Survival Curves That Incorporate Marked Censoring Times. MDM Policy Pract. 2022; 7(1):23814683221077643. PMC: 8808036. DOI: 10.1177/23814683221077643. View