Calabrò L, et al. - In patients with malignant mesothelioma, researchers investigated the efficacy and safety of first-line or second-line tremelimumab combined with durvalumab, an anti-PD-L1 monoclonal antibody. As per outcomes, the combination of tremelimumab and durvalumab seemed active, with a good safety profile in these patients.

Methods

• Researchers performed an open-label, non-randomised, phase 2 trial enrolling patients with unresectable pleural or peritoneal mesothelioma.
• The patients received intravenous tremelimumab (1 mg/kg bodyweight) and durvalumab (20 mg/kg bodyweight) every 4 weeks for four doses, followed by maintenance intravenous durvalumab at the same dose and schedule for nine doses.
• The proportion of patients with an immune-related objective response according to the immune-related modified Response Evaluation Criteria in Solid Tumors (RECIST; for pleural mesothelioma) or immune-related RECIST version 1.1 (for peritoneal mesothelioma) was assessed as the primary endpoint.
• They performed the primary analysis by intention to treat.
• Patients who received at least one dose of study drug were included in the safety analysis.

Results

• Researchers enrolled 40 patients with mesothelioma from Oct 30, 2015, to Oct 12, 2016; the patients received at least one dose each of tremelimumab and durvalumab.
• For a median of 19·2 months (IQR 13·8–20·5), follow-up of the patients was performed .
• An immune-related objective response was noted in 11 (28%) of 40 patients (all partial responses; confirmed in ten patients); median response duration was 16·1 months (IQR 11·5–20·5).
• Immune-related disease control was noted in 26 (65%) patients; of these, 25 (63%) demonstrated disease control.
• Observations revealed median immune-related progression-free survival of 8·0 months (95% CI 6·7–9·3), median progression-free survival of 5·7 months (1·7–9·7), and median overall survival of 16·6 months (13·1–20·1).
• No correlation of baseline tumour PD-L1 expression was noted with the proportion of patients who had an immune-related objective response or immune-related disease control, with immune-related progression-free survival, or with overall survival.
• Treatment-related adverse events of any grade were encountered in 30 (75%) patients; 7 of whom (18%) experienced grade 3–4 treatment-related adverse events.
• They encountered treatment-related toxicity that was generally manageable and reversible with protocol guidelines.