PMID- 35358809 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220512 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 166 DP - 2022 May TI - Systemic therapy for pre-treated malignant mesothelioma: A systematic review, meta-analysis and network meta-analysis of randomised controlled trials. PG - 287-299 LID - S0959-8049(22)00129-0 [pii] LID - 10.1016/j.ejca.2022.02.030 [doi] AB - BACKGROUND: Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of clinical uncertainty about the choice of active treatment in this poor prognosis malignancy. METHODS: To compare the effectiveness and safety and weigh the benefit of different systemic treatments in patients with pre-treated mesothelioma by systematic review, meta-analysis and network meta-analysis of RCTs. Full-text articles and abstracts were searched on PubMed, EMBASE, Cochrane Library and oncology conferences proceedings from 2005 through November 2021 for phase 2 and 3 RCTs. The protocol was submitted to the PROSPERO registry. Reporting followed the PRISMA guideline. Outcomes of interest were overall survival (OS) and progression-free (PFS), grade >/=3 treatment-related (Tr) adverse events (AEs), Tr-deaths and Tr-AEs leading to treatment discontinuation. FINDINGS: Nine trials at low risk of bias by Cochrane Collaboration's methodology were included, encompassing 2789 patients. Five studies showed PFS benefit in the experimental treatment. In two studies, OS was prolonged by immunotherapy (versus placebo) or by adding an antiangiogenic agent to chemotherapy. Reported Tr-AE were lower with single-agent anti-PD1 compared with chemotherapy or placebo. The meta-analysis revealed a beneficial global effect on OS and PFS from experimental treatments (HR 0.86, 95% CI 0.77-0.96, p = 0.0083 and HR 0.79, 95% CI 0.72-0.86, p < 0.001), that for the PFS significantly favoured the comparison with non-active treatments (HR 0.73, 95% CI 0.66-0.81, p < 0.001). Younger patients (i.e. <65-70 years) appeared to benefit the most in OS (HR 0.71, 95% CI 0.55-0.92, p = 0.04). The risk of serious Tr-AEs and Tr-deaths was not significantly increased by experimental treatments (RR 1.38, 95% CI 0.81-2.35, p = 0.24 and RR 2.07, 95% CI 0.69-6.24, p = 0.19, respectively) that instead increased TrAEs leading to treatment discontinuation (RR 2.9, 95% CI 1.44-6.08, p = 0.003). The network meta-analysis did not identify any superior treatment in PFS. INTERPRETATION: For patients with pre-treated MPM, single-agent anti-PD1 or chemotherapy +/- the antiangiogenic agent can be considered active and safe systemic therapeutic options, particularly for younger patients. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Banna, Giuseppe Luigi AU - Banna GL AD - Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy. Electronic address: giuseppe.banna@ircc.it. FAU - Signori, Alessio AU - Signori A AD - Department of Health Sciences Section of Biostatistics, University of Genova, Genoa, Italy. FAU - Curioni-Fontecedro, Alessandra AU - Curioni-Fontecedro A AD - Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland. FAU - Cortellini, Alessio AU - Cortellini A AD - Department of Surgery and Cancer, Imperial College London, Faculty of Medicine, Hammersmith Hospital, London, United Kingdom. FAU - Ponzano, Marta AU - Ponzano M AD - Department of Health Sciences Section of Biostatistics, University of Genova, Genoa, Italy. FAU - Giunta, Emilio Francesco AU - Giunta EF AD - Department of Experimental Medicine, Universita Degli Studi Della Campania Luigi Vanvitelli, Naples, Italy. FAU - Rebuzzi, Sara Elena AU - Rebuzzi SE AD - Medical Oncology, Ospedale San Paolo, Savona, Italy. FAU - Chan, Samuel AU - Chan S AD - Oncology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom. FAU - Gebbia, Vittorio AU - Gebbia V AD - La Maddalena Cancer Center, Palermo, Italy. FAU - van Eeden, Ronwyn AU - van Eeden R AD - The Medical Oncology Centre of Rosebank, University of the Witwatersrand, Johannesburg, South Africa. FAU - Addeo, Alfredo AU - Addeo A AD - Department of Oncology, Geneva University Hospital, Geneve, Switzerland. FAU - Ottensmeier, Christian AU - Ottensmeier C AD - Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20220328 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal) SB - IM MH - Angiogenesis Inhibitors/adverse effects MH - *Antibodies, Monoclonal/therapeutic use MH - Humans MH - Immunotherapy/methods MH - *Mesothelioma, Malignant MH - Network Meta-Analysis OTO - NOTNLM OT - CTLA4 OT - Chemotherapy OT - Immunotherapy OT - Mesothelioma OT - Meta-analysis OT - Network meta-analysis OT - PD1 OT - Pre-treated OT - Randomised controlled trials OT - Systematic review COIS- Conflict of Interest statement AA reported personal fees from BMS, AstraZeneca, Boehringer-Ingelheim, Roche, MSD, Pfizer, Eli Lilly, Astellas. AC reported fees from Astrazeneca, MSD, BMS, Roche, Novartis, Eisai. ACF reports personal fees from Astrazeneca, BMS, Boehringer-Ingelheim, Pfizer, Roche, Takeda, MSD, Janssen-Cilag. CO reports personal fees from BMS. GLB reported personal fees from Astellas, Astrazeneca. RvE reports personal fees from Roche, Novartis, Takeda, MSD. SER reported fees from Amgen, BMS, GSK, Astellas, Roche; support for attending meeting from MSD and BMS. All other authors declare no competing interests. EDAT- 2022/04/01 06:00 MHDA- 2022/04/27 06:00 CRDT- 2022/03/31 20:13 PHST- 2022/02/20 00:00 [received] PHST- 2022/02/27 00:00 [accepted] PHST- 2022/04/01 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/03/31 20:13 [entrez] AID - S0959-8049(22)00129-0 [pii] AID - 10.1016/j.ejca.2022.02.030 [doi] PST - ppublish SO - Eur J Cancer. 2022 May;166:287-299. doi: 10.1016/j.ejca.2022.02.030. Epub 2022 Mar 28.