The FDA has approved [ Keytruda (pembrolizumab) ] plus pemetrexed and platinum chemotherapy in the frontline treatment of patients with unresectable advanced or metastatic malignant pleural mesothelioma.
Data from the phase 2/3 KEYNOTE-483 study (NCT02784171) showed that [ Keytruda (pembrolizumab) ] plus chemotherapy (n = 222) significantly improved overall survival (OS) vs chemotherapy alone (n = 218), with a median OS of 17.3 months (95% CI, 14.4-21.3) and 16.1 months (95% CI, 13.1-18.2), respectively (HR, 0.79; 95% CI, 0.64-0.98; P =.0162).
Moreover, the median progression-free survival was 7.1 months in both the investigative (95% CI, 6.9-8.1) and control (95% CI, 6.8-7.7) arms, respectively (HR, 0.80; 95% CI, 0.65-0.99; P =.0194); this translated to a 20% reduction in the risk of disease progression or death. The confirmed objective response rate was also higher with the addition of [ Keytruda (pembrolizumab) ] to chemotherapy vs chemotherapy alone, at 52% (95% CI, 45.5%-59.0%) and 29% (95% CI, 23.0%-35.4%), respectively. The median duration of response in the respective arms was 6.9 months (95% CI, 5.8-8.3) and 6.8 months (95% CI, 5.5-8.5).
The study enrolled patients with unresectable advanced or metastatic malignant pleural mesothelioma. Patients needed to have measurable disease by modified RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and acceptable hematological, liver, and renal function. They could not have previously received systemic therapy in the advanced setting, a contraindication to immunotherapy, no other active malignancy, and no known central nervous system metastases unless treated and stable.
Study participants were randomly assigned 1:1 to receive [ Keytruda (pembrolizumab) ] every 3 weeks for up to 2 years plus pemetrexed and platinum-based chemotherapy for up to 6 cycles or pemetrexed and platinum-based chemotherapy for up to 6 cycles. Chemotherapy consisted of cisplatin at 75 mg/m2 or carboplatin at area under the curve 5 or 6 and pemetrexed at 500 mg/m2. Patients were stratified by histology.
The main efficacy outcome measure was OS and additional efficacy measures included PFS, ORR, and DOR per blinded independent central review and according to modified RECIST 1.1 criteria for mesothelioma.
Data from exploratory OS analyses showed that in those with epithelioid disease (n = 345), the median OS in the [ Keytruda (pembrolizumab) ] /chemotherapy and chemotherapy arms were 19.8 months (95% CI, 16.0-22.2) and 18.2 months (95% CI, 16.0-20.4), respectively (HR, 0.89; 95% CI, 0.70-1.13).2 The estimated 3-year OS rates were 26% (19%-34%) and 20% (14%-28%). The median PFS was 7.13 months (95% CI, 6.9-8.1) in the [ Keytruda (pembrolizumab) ] arm vs 7.39 months (95% CI, 7.0-8.4) in the chemotherapy arm (HR, 0.93; 95% CI, 0.1-1.2).
In those with non-epithelioid disease (n = 95), the median OS with [ Keytruda (pembrolizumab) ] plus chemotherapy was 12.3 months (95% CI, 8.67-21.2) vs 8.2 months (95% CI, 5.85-10.8) with chemotherapy alone (HR, 0.57; 95% CI, 0.36-0.89). The respective 3-year OS rates were 23% (13%-40%) and 7% (2%-21%). The median PFS was 6.9 months (95% CI, 4.5-9.7) in the [ Keytruda (pembrolizumab) ] arm vs 4.5 months (95% CI, 4.0-6.4) in the chemotherapy arm (HR, 0.48; 95% CI, 0.3-0.8). [Footnotes omitted] [Article continues at original source, with footnotes]
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