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Cited by 968Occupational and environmental lung diseasesIntraperitoneal and Appendiceal MalignanciesPleural and Pulmonary Diseases

Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): A randomised, controlled, open-label, phase 3 trial

Zalcman, Gérard, Mazieres, Julien, Margery, Jacques, Greillier, Laurent, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Molinier, Olivier, Corre, Romain +13 more·2016·The Lancet
DOI 10.1016/s0140-6736(15)01238-6
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Abstract

Background Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma.Methods In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0·8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m(2) pemetrexed plus 75 mg/m(2) cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456.Findings From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18·8 months [95% CI 15·9-22·6]) than with PC (16·1 months [14·0-17·9]; hazard ratio 0·77 [0·62-0·95]; p=0·0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC.Interpretation Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease.Funding Intergroupe Francophone de Cancérologie Thoracique (IFCT).

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  • A randomized controlled open-label phase III clinical trial in malignant pleural mesothelioma patients reported a median overall survival of 16.1 months in its control arm of pemetrexed and cisplatin.

    “Of note, a randomized controlled open-label phase III clinical trial in MPM patients published in 2016 demonstrated a median OS in its control arm (pemetrexed and cisplatin) of 16.1 months [15].”

    From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [15]

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Authors
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, M.-P., Morin, F., Creveuil, C., Parienti, J.-J., & Scherpereel, A.
Affiliations
  • Inserm (FR)
  • Institut Gustave Roussy (FR)
  • Assistance Publique Hôpitaux de Marseille (FR)
  • Centre Hospitalier Intercommunal Toulon-La Seyne-sur-Mer (FR)
  • Centre Hospitalier du Mans (FR)
  • Hôpital Pontchaillou (FR)
  • Hôpital Intercommunal de Créteil (FR)
  • Hôpital d'instruction des Armées Percy (FR)
  • Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
  • Centre François Baclesse (FR)
  • Intergroupe Francophone de Cancérologie Thoracique (FR)
  • Normandie Université (FR)
Corresponding author
Zalcman, Gérard
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2016-04
Volume
387
Issue
10026
Pages
1405-1414
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(15)01238-6
OpenAlex
W2215044613
Cited by
968
References
37
Citations by year
2026: 27 · 2025: 60 · 2024: 73 · 2023: 93 · 2022: 125 · 2021: 138 · 2020: 116 · 2019: 88 · 2018: 109 · 2017: 83 · 2016: 50 · 2015: 2 · 2014: 1 · 2012: 1
FWCI
64.33
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ligue Contre le Cancer
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
  • Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pleural and Pulmonary Diseases
Keywords
malignant pleural mesothelioma, bevacizumab, cisplatin, pemetrexed, first-line chemotherapy, vascular endothelial growth factor inhibition, overall survival, smoking status, antiplatelet agents, anti-inflammatory agents, anti-angiogenic therapy, asbestos exposure, pleural effusion
MeSH terms
Bevacizumab, Pemetrexed, Mesothelioma, Malignant, Aged, Antineoplastic Combined Chemotherapy Protocols, Cisplatin, Creatinine, Female, Humans, Hypertension, Lung Neoplasms, Male, Mesothelioma, Middle Aged, Pleural Neoplasms, Proteinuria, Thrombosis, Vascular Endothelial Growth Factor A

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