Nivolumab, pembrolizumab promising in malignant mesothelioma
Data from phase Ib and II trials presented at the 17th World Conference on Lung Cancer (WCLC) show promising efficacy of nivolumab and pembrolizumab in patients with malignant mesothelioma, a highly aggressive cancer with poor prognosis and limited treatment options after progression on platinum-containing chemotherapy.
In a phase II study on 34 patients with malignant pleural mesothelioma (MPM) that progressed after ≥1 prior therapy, nivolumab (3 mg/kg every 2 weeks) treatment resulted in partial response (PR) in five patients and stable disease (SD) in 12 patients after 12 weeks. Disease control rate (DCR) at 12 weeks, the study’s primary endpoint, was 50 percent. [WCLC 2016, abstract OA13.01]
“At 24 weeks, four patients had a PR and seven had SD, yielding a DCR rate of 33 percent. Median progression-free survival [PFS] was 110 days,” reported Dr Paul Baas of the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Grade 3/4 adverse events (AEs) occurred in eight patients and included nausea and vomiting (n=2 each), pneumonitis, pericardial effusion, infection and infusion-related reaction (n=1 each).
“PD-L1 expression ≥1 percent was found in 29 percent of patients. Three of the 20 patients with no PD-L1 expression achieved PR, while eight had SD. PR and SD were also observed in patients with PD-L1 expression,” said Baas.
In another phase II study that evaluated pembrolizumab (200 mg IV every 21 days) in 34 patients with malignant mesothelioma, PR and SD were seen in seven and 20 patients, respectively, yielding a response rate (RR) of 21 percent and a DCR of 80 percent. Median PFS was 6.2 months, while median overall survival (OS) was 11.9 months. [WCLC 2016, abstract OA13.02]
“Patients in the study had MPM or peritoneal malignant mesothelioma that progressed on or after 1–2 prior regimens including pemetrexed or platinum,” said Professor Hedy Kindler of the University of Chicago, Illinois, US.
“The RR was lower in patients without PD-L1 expression vs those with expression [12 vs 27 percent]. However, there was no significant difference in PFS [p=0.38] or OS [p=0.25],” she added. “The most common grade 3/4 AEs were pneumonitis [6 percent], fatigue [6 percent] and adrenal insufficiency (6 percent].”
Similarly, a DCR rate of 72 percent was seen in 25 patients with advanced, PD-L1–positive MPM who received pembrolizumab (10 mg/kg every 2 weeks) in the phase Ib KEYNOTE-028 study. Five patients achieved PR, while 13 had stable disease. The objective RR was 20 percent, clinical benefit rate was 40 percent, and median duration of response was 12 months. [WCLC 2016, abstract OA13.03]
“Median PFS was 5.4 months, while median OS was 18 months,” reported Dr Evan Alley of the Penn Mesothelioma and Pleural Program, Penn Medicine, Philadelphia, Pennsylvania, US. “Grade ≥3 AEs occurred in five patients.”