Pembrolizumab regimen ‘ticks all the efficacy boxes’ for advanced mesothelioma
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Key takeaways:
- The trial met its primary endpoint, showing significant improvement in OS with the pembrolizumab regimen vs. chemotherapy alone.
- The pembrolizumab regimen decreased risk for death by 21%.
CHICAGO — The addition of pembrolizumab to chemotherapy significantly extended OS as first-line therapy for adults with advanced malignant pleural mesothelioma, according to results of the randomized phase 3 IND.227/KEYNOTE-483 trial.
The data, presented at ASCO Annual Meeting, showed the pembrolizumab-containing regimen reduced the risk for death by 21% compared with chemotherapy alone.
“It ticks all the efficacy boxes,” Scott A. Laurie, MD, FRCPC, a researcher and thoracic medical oncologist at The Ottawa Hospital and associate professor of medicine in the division of medical oncology at University of Ottawa, told Healio. "This familiar regimen — one oncologists already use routinely in the management of non-small cell lung cancer — should become a new therapeutic option for patients with advanced pleural mesothelioma.”
Background, methodology
The phase 2 portion of the IND.227/KEYNOTE-483 trial showed “promising results” for both the use of pembrolizumab (Keytruda, Merck) as monotherapy and in combination with chemotherapy for treatment of advanced malignant pleural mesothelioma, Laurie said.
The Canadian Cancer Trials Group — in collaboration with National Cancer Institute of Naples and Intergroupe Francophone de Cancérologie Thoracique — conducted the randomized phase 3 IND.227/KEYNOTE-483 trial to assess the safety and efficacy of adding of the anti-PD-1 therapy pembrolizumab to chemotherapy for patients with unresectable advanced or metastatic pleural mesothelioma.
The study included 440 patients randomly assigned to receive pemetrexed and cisplatin with or without pembrolizumab dosed at 200 mg every 3 weeks for up to 35 cycles.
OS — defined as time from randomization to the date of death from any cause — served as the study’s primary endpoint. Secondary endpoints included objective response rate and safety.
Key findings
The trial met its primary endpoint, with pembrolizumab plus chemotherapy conferring a significant improvement in OS compared with chemotherapy alone (HR = 0.79; 95% CI, 0.64-0.98).
Investigators reported a 62.2% objective response rate among those who received pembrolizumab plus chemotherapy compared with 38.1% for those who received chemotherapy alone (P < .0001).
Researchers also observed significantly improved PFS among study participants who received pembrolizumab plus chemotherapy (HR for disease progression or death = 0.8; 95% CI, 0.65-0.99).
Pembrolizumab plus chemotherapy resulted in a 1-year PFS rate of 26% compared with 17% among those who received chemotherapy only.
Grade 3 or grade 4 treatment-related adverse events occurred more frequently in the pembrolizumab group compared with those who received chemotherapy only (27% vs. 15%). However, the safety profile of the pembrolizumab regimen used in IND.227/KEYNOTE-483 is comparable to what researchers have observed using immunotherapies in similar patient populations, including the phase 3 KEYNOTE-189 trial for individuals with non-small cell lung cancer.
Clinical implications
The pembrolizumab-chemotherapy regimen gives clinicians an effective second option to consider for previously untreated malignant plural mesothelioma, according to Laurie.
“Oncologists will need to make their choice based on what's best for the patient in front of them, but we believe this pembrolizumab regimen is a viable, perhaps preferable alternative to first-line therapy with nivolumab [Opdivo, Bristol Myers Squibb] and ipilimumab [Yervoy, Bristol Myers Squibb],” he told Healio.
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Chu QS, et al. Abstract LBA8505. Presented at: ASCO Annual Meeting; June 2-6, 2022; Chicago.
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