Treatment with pembrolizumab (Keytruda) and first-line chemotherapy resulted in a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with unresectable advanced or metastatic malignant pleural mesothelioma, according to a press release from Merck on the final analysis of the phase 2 /3 study CCTG IND.227/KEYNOTE-483 (NCT02784171).
The safety profile of the combination appeared consistent with previous findings. The results of the study are to be read at an upcoming medical congress and discussed with global regulatory authorities.
“Malignant pleural mesothelioma is a rapidly progressive cancer that develops in the lining of the lungs and has a poor prognosis,” said Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories press release. “Patients need new treatments that can improve survival, and these positive results support the potential of [pembrolizumab] in combination with chemotherapy as first-line therapy for patients with the most common form of malignant mesothelioma.”
A total of 440 patients were enrolled in the randomized, open-label, Phase 3 portion of the CCTG IND.227/KEYNOTE-483 study, who were randomized to receive either pembrolizumab 200 mg every 3 weeks for up to 35 cycles plus pemetrexed 500 mg/m2 and 75 mg/m2 cisplatin every 3 weeks for 6 cycles or the chemotherapy backbone alone; Substitution with carboplatin was allowed.
The primary endpoints of the study were OS and progression-free survival, secondary endpoints were objective response rate by blinded independent central review, safety and quality of life.
To be included in the study, patients had to have histologically confirmed malignant pleural mesothelioma that was untreatable with standard therapies and be eligible for treatment with standard chemotherapy without contraindications. Additional inclusion criteria were the presence of radiologically documented disease, age 18 years and older, an ECOG performance status of 0 or 1, and the presence of all radiological studies within 21 days of study registration.
Patients diagnosed with immunodeficiency or requiring systemic steroid therapy, with an active autoimmune disease requiring systemic treatment, or who have not received a live vaccine within 30 days of initiating therapy were not eligible for enrollment . Additional exclusion criteria were active central nervous system metastases, untreated and/or uncontrolled cardiovascular disease, a history of other malignancies, or a history of allergic reactions to compounds similar to pembrolizumab or to the chemotherapeutic agents included in the study.
reference
KEYTRUDA® (pembrolizumab) plus chemotherapy significantly improved overall survival over chemotherapy alone as first-line treatment for advanced malignant pleural mesothelioma. press release. note March 10, 2023. Accessed March 10, 2023. http://bit.ly/4240463
