Pembrolizumab has shown activity in patients with diffuse malignant peritoneal mesothelioma, according to a study published in JAMA Network Open.
The study showed no significant difference in outcomes according to PD-L1 status or histology, but patients with nonepithelioid tumors had a numeric benefit in progression-free survival (PFS) and overall survival (OS).
This retrospective study included 24 patients with diffuse malignant peritoneal mesothelioma. Eighteen patients had epithelioid histology, 4 had biphasic histology, and 1 patient each had sarcomatoid and desmoplastic histology. Six patients had PD-L1-positive tumors, 11 had PD-L1-negative tumors, and 7 had unknown PD-L1 status.
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The patients’ median age at diagnosis was 62 years. Most patients (95.8%) had previously received intravenous systemic chemotherapy, 66.7% had undergone cytoreductive surgery, and 33.3% had prior intraperitoneal chemotherapy.
The patients received pembrolizumab (at 200 mg or 2 mg/kg every 21 days) for a median of 7 cycles (range, 1-42 cycles).
Nineteen patients had radiologic data and were evaluable for response. The objective response rate was 21.1%. Four patients had a partial response, 10 had stable disease, and 5 had progressive disease.
At a median follow-up of 29.2 months, the median PFS was 4.9 months, and the median OS was 20.9 months.
The median PFS was similar regardless of PD-L1 status — 3.1 months among PD-L1-positive patients and 5.7 months among PD-L1-negative patients.
There was a numeric benefit in PFS and OS among patients with nonepithelioid histology, but statistical significance was not reached. The median PFS was 11.5 months for patients with nonepithelioid tumors and 4.0 months for patients with epithelioid tumors (P =.24). The median OS was 31.8 months and 17.5 months, respectively (P =.24).
The researchers noted that 3 patients had PFS lasting 2 years or more. The first patient had epithelioid histology, unknown PD-L1 status, stable disease as their best response, and a 2% change in tumor size.
The second patient had desmoplastic histology, was PD-L1 negative, had stable disease as their best response, and had a -21% change in tumor size. The third patient had biphasic histology, 80% PD-L1 status, a partial response, and a -70% change in tumor size.
“[T]hese preliminary data suggest that pembrolizumab has clinical activity in DMPM [diffuse malignant peritoneal mesothelioma],” the researchers concluded. “Future immunotherapy trials in DMPM should leverage novel immunotherapy targets and a multi-institutional approach to increase the sample size and power to detect disease response and determine the predictive role of histology and biomarkers in this rare disease.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Marmarelis ME, Wang X, Roshkovan L, et al. Clinical outcomes associated with pembrolizumab monotherapy among adults with diffuse malignant peritoneal mesothelioma. JAMA Netw Open. Published online March 10, 2023. doi:10.1001/jamanetworkopen.2023.2526
