Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study

Aims Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis and limited treatment options. Cisplatin plus pemetrexed is the only approved first‐line treatment for patients with unresectable MPM. Recently, promising outcomes were observed with first‐line bevacizumab combined with cisplatin/pemetrexed, leading to the recommendation of this regimen as a first‐line treatment option for patients with MPM. Bevacizumab plus cisplatin/pemetrexed has been shown to be safe and effective in non–small cell lung cancer, however, there are no efficacy or safety data in Japanese patients with MPM treated with this regimen. We conducted a multicenter study to evaluate tolerability and safety for Japanese patients with chemotherapy‐naïve, unresectable MPM. Methods Eligible patients (n = 7) received bevacizumab plus cisplatin/pemetrexed (up to six cycles), then single‐agent bevacizumab until disease progression or onset of unacceptable adverse events (AEs), according to the 3+3 design analogy. Results One patient (14.3%) reported an AE (gastric ulcer) meeting tolerability criteria. All patients experienced gastrointestinal disorders, including nausea (grade 1/2 only, n = 6, 85.7%) and constipation (grade 1/2 only, n = 5, 71.4%). Five patients (71.4%) had grade 3 hypertension. Two patients discontinued treatment due to gastric ulcer (n = 1) and proteinuria (n = 1). At data cut‐off, four patients had stable disease, two had partial response and one had non‐complete response/non‐progressive disease due to the absence of target lesions. Conclusions Bevacizumab plus cisplatin/pemetrexed then bevacizumab was well tolerated in Japanese patients with MPM. The addition of bevacizumab to standard cisplatin/pemetrexed showed survival benefit in mesothelioma patients, leading to its recommendation as a first‐line treatment option. Until now, there have been no tolerability or safety data for the triplet combination in Japanese mesothelioma patients. We evaluated this triplet combination for Japanese mesothelioma patients in a clinical trial according to the 3+3 design analogy and demonstrated its safety and tolerability.