Adding Pembrolizumab to Chemotherapy for Previously Untreated Advanced Pleural Mesothelioma

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As reported in The Lancet by Chu et al, a phase III trial conducted in Canada, Italy, and France showed that the addition of pembrolizumab to chemotherapy improved survival in previously untreated patients with advanced pleural mesothelioma.

Study Details

In the multicenter open-label trial, 440 patients were randomly assigned between January 2017 and September 2020 to receive cisplatin at 75 mg/m² or carboplatin at area under the curve = 5–6 plus pemetrexed at 500 mg/m² every 3 weeks for up to six cycles with (n = 222) or without (n = 218) pembrolizumab at 200 mg every 3 weeks for up to 2 years. Patients had a median age of 71 years (interquartile range [IQR] = 66–75 years). The primary endpoint was overall survival in all randomly assigned patients.

Overall Survival

At final analysis (database lock in December 2022), median follow-up was 16.2 months (IQR = 8.3–27.8 months). Median overall survival was 17.3 months (95% confidence interval [CI] = 14.4–21.3 months) in the pembrolizumab group vs 16.1 months (95% CI = 13.1–18.2 months) in the control group (hazard ratio [HR] = 0.79, 95% CI = 0.64–0.98, P = .0324). Rates at 2 and 3 years were 39% (95% CI = 33%–46%) vs 33% (95% CI = 27%–40%) and 25% (95% CI = 20%–33%) vs 17% (95% CI = 13%–24%). Hazard ratios favored the pembrolizumab group in both the PD-L1–positive and PD-L1–negative subgroups.

Median progression-free survival was 7.13 months (95% CI = 6.9–8.1 months) in the pembrolizumab group vs 7.16 months (95% CI = 6.8–7.7 months) in the control group (HR = 0.80, 95% CI = 0.65–0.99, P = .0372). Rates at 1 year were 26% (95% CI = 21%–33%) vs 17% (95% CI = 12%–23%).

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in 27% of patients in the pembrolizumab group and 15% of those in the control group, most commonly fatigue (7%) and nausea (5%) in the pembrolizumab group and fatigue (6%) in the control group. Hospital admissions for treatment-related serious adverse events occurred in 18% vs 6% of patients. The pembrolizumab group had higher rates of blood transfusions (25% vs 16%), platelet transfusions (5% vs 1%) and febrile neutropenia (5% vs 1%). Treatment-related adverse events led to death in seven patients (3%) in the pembrolizumab group vs two patients (1%) in the control group.

The investigators concluded, “In patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum/pemetrexed chemotherapy was tolerable and resulted in a significant improvement in overall survival. This regimen is a new treatment option for previously untreated advanced pleural mesothelioma.”

Lesley Seymour, MD, of the Canadian Cancer Trials Group, Kingston, Ontario, is the corresponding author for The Lancet article.

Disclosure: The study was funded by The Canadian Cancer Society and Merck & Co. For full disclosures of the study authors, visit

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