Pembrolizumab active in diffuse malignant peritoneal mesothelioma
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Pembrolizumab demonstrated clinical activity among patients with diffuse malignant peritoneal mesothelioma, regardless of PD-L1 status or histology, according to data published in JAMA Network Open.
“In clinic, we have seen some people experience durable clinical benefit from pembrolizumab, so I was not surprised to find that we had a number of long-term responders,” Melina E. Marmarelis, MD, MSCE, assistant professor of medicine at Hospital of the University of Pennsylvania, told Healio. “The overall response rate is in line with the response rate for immunotherapy in other malignancies, so I think this data confirms that pembrolizumab is an active drug in this disease.”
Diffuse malignant peritoneal mesothelioma (DMPM), an uncommon form of malignant mesothelioma that arises from the peritoneum, has been associated with median OS of 9 to 100 months.
Pembrolizumab (Keytruda, Merck) has shown activity in diffuse pleural mesothelioma; however, limited data are available for DMPM.
Researchers conducted a retrospective cohort study of adults with DMPM treated between Jan. 1, 2015, and Sept. 1, 2019, at either University of Pennsylvania’s Abramson Cancer Center or Memorial Sloan Kettering Cancer Center.
The study included 24 patients (median age, 62 years; interquartile range, 52.4-70.6; 58.3% women; 79.2% white) who received either 200 mg or 2 mg/kg pembrolizumab monotherapy every 21 days. All but one patient received a median two lines (range, 0-6 lines) of systemic chemotherapy before pembrolizumab.
Researchers evaluated median PFS and median OS using Kaplan-Meier estimates. They determined the best overall response using RECIST version 1.1 and used the Fisher exact test to assess associations of disease features with partial response.
Of the 17 patients who underwent PD-L1 testing, six (35.3%) exhibited positive tumor PD-L1 expression (range, 1% to 80%).
Four of 19 evaluable patients (21%) exhibited a partial response (ORR = 21.1%; 95% CI, 6.1-46.6), whereas 10 (52.6%) had stable disease and five (26.3%) had progressive disease.
Researchers did not note an association between partial response and presence of a BAP1 alteration, PD-L1 positivity or nonepithelioid histology.
At a median follow-up of 29.2 months (95% CI, 19.3-not available), results showed median PFS of 4.9 months (95% CI, 2.8-13.3) and median OS of 20.9 months (95% CI, 10-not available). Three patients (12.5%) experienced PFS of more than 2 years.
Patients with nonepithelioid histology experienced a numerical advantage over patients with epithelioid histology in both median PFS (11.5 months vs. 4 months) and median OS (31.8 months vs. 17.5 months), although the difference fell short of statistical significance, according to researchers.
Marmarelis told Healio she hopes the results support inclusion of pembrolizumab in National Comprehensive Cancer Network guidelines for peritoneal mesothelioma.
“Second, I think this could be a good option for patients not eligible for dual checkpoint blockade with ipilimumab (Yervoy, Bristol Myers Squibb) or nivolumab (Opdivo, Bristol Myers Squibb).
“We still have work to do in deciphering who benefits most from immunotherapy. In this study, we saw a signal that patients with nonepithelioid histology may have benefited more from pembrolizumab than those with epithelioid histology, but we will need to confirm this in future studies,” she added.
For more information:
Melina E. Marmarelis, MD, MSCE, can be reached at Perelman Center for Advanced Medicine, 3400 Civic Center Blvd., 10th floor, South Tower, Philadelphia, PA 19104; email: melina.marmarelis@pennmedicine.upenn.edu.
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Marmarelis ME, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2023.2526.
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