Expert Point of View: Melina E. Marmarelis, MD, MSCE

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Invited study discussant, Melina E. Marmarelis, MD, MSCE, of Abramson Cancer Center at the University of Pennsylvania, Philadelphia, noted that pembrolizumab has been evaluated in advanced mesothelioma in several clinical trials, with varying results. According to Dr. Marmarelis, this high variability is likely due to differences in patient enrollment, such as the line of therapy, PD-L1 level, and varying sample sizes.

“Of note, although some trials reported a trend in better outcomes for higher PD-L1 expression, others did not. It still remains unclear whether PD-L1 status is predictive of better responses to immunotherapy in malignant pleural mesothelioma,” she said.

“Interestingly, partial responses were seen in both the PD-L1–positive and –negative groups in this study, further supporting that PD-L1 status is not predictive of response to pembrolizumab in mesothelioma,” she continued. “Although the overall response rate, progression-free survival, and overall survival are not particularly impressive, the duration of response in the 10 patients with a partial response was surprising.”

Words of Caution

Although the group of responders was small, said Dr. Marmarelis, the impressive duration of response highlights the need for appropriate patient selection for this treatment. The baseline characteristics were as expected, with a mix of PD-L1–positive and –negative tumors as well as epithelioid and nonepithelioid histology. However, the nonepithelioid population (31%) was “larger than usual” in a trial of malignant pleural mesothelioma.

“We don’t have information on the outcomes in these nonepithelioid patients, but with only 10 patients with a partial response, this type of subset analysis could be misleading,” she added.

Should Histology Drive Treatment Decisions?

According to Dr. Marmarelis, the predictive role of malignant pleural histologies has come to the forefront of discussions on immunotherapy and mesothelioma, given the recently reported CheckMate 743 trial. This study evaluated ipilimumab and nivolumab in comparison to chemotherapy in the front-line setting. Although a similar median overall survival was observed in both histology groups treated with dual checkpoint inhibitors, the nonepithelioid group treated with chemotherapy did considerably worse than the nonepithelioid group treated with immunotherapy.

“This raises the possibility that treatment choices in malignant pleural mesothelioma may need to be driven by histology,” Dr. Marmarelis concluded. “More research is needed to improve patient selection for this approach.” 

DISCLOSURE: Dr. Marmarelis holds stock or other ownership interests in Bluebird Bio, Gilead Sciences, Johnson & Johnson, Merck, Pfizer, and Portola Pharmaceuticals; has received honoraria from Novocure and Targeted Oncology; has an immediate family member who has received honoraria from Health Advances; has served as a consultant or advisor to AstraZeneca and Boehringer Ingelheim; has received institutional research funding from AstraZeneca, Lilly, and Trizell; has been reimbursed for travel, accommodations, or other expenses by Boehringer Ingelheim and Novocure; and has held other relationships with Novartis.

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