Research in context
Evidence before this study
We searched MEDLINE for full-text articles published from Jan 1, 2000, to Dec 31, 2014, in English or French, reporting phase 3, randomised, clinical trials and phase 2 studies relevant to our study. We used the terms “mesothelioma”, “bevacizumab”, “angiogenic inhibitors”, and “chemotherapy”. We found that the standard of care for medical treatment of mesothelioma is pemetrexed plus cisplatin on the basis of a phase 3 study done in 2003 reporting a 12·1 month overall survival (OS) that exceeds 13 months in patients receiving vitamins B9 and B12. Angiogenic inhibitors as monotherapies were reported with modest efficacy because of the role of vascular endothelial growth factor in mesothelioma biology. Investigators of three phase 2 studies reported interesting results with the triple association of the angiogenic drug bevacizumab and a platinum-based doublet with either gemcitabine or pemetrexed. However, no phase 3 data had been reported for addition of bevacizumab to the present standard of care (pemetrexed and cisplatin).
Added value of this study
A pemetrexed-based chemotherapy doublet was recommended as a treatment option for malignant pleural mesothelioma by the 2007 National Institute for Health and Care Excellence guidance that was in place at the beginning of our study for patients with WHO performance statuses of 0 or 1 deemed to have advanced disease and for whom surgical intervention was deemed inappropriate. Findings from our study of bevacizumab plus pemetrexed and cisplatin compared with pemetrexed and cisplatin alone showed a significantly improved median OS and progression-free survival with addition of bevacizumab. Mesothelioma traditionally has a poor prognosis; however, in our study, patient subgroups that have previously shown poor prognosis benefited as much as other subgroups from addition of bevacizumab, including those with an ECOG performance status of 2, a haemoglobin concentration of ≤140 g/L, thrombocytosis, a leucocyte count of 8·3 × 109/L or higher, or sarcomatoid or mixed histology. Therefore, these data show an alternative to present options that have not been improved on since the pivotal study by Vogelzang and colleagues of pemetrexed plus cisplatin more than 10 years ago.
Implications of all the available evidence
Addition of bevacizumab to the present standard of care cisplatin and pemetrexed significantly increased OS and progression-free survival in mesothelioma, with manageable toxic effects. We believe that this result has important implications for future first-line treatment of mesothelioma because the pemetrexed plus cisplatin plus bevacizumab regimen should be considered as a new treatment option for patients with newly diagnosed mesothelioma who are eligible to receive bevacizumab and who are not candidates for curative-intent surgery.