The final analysis of the phase 2/3 CCTG IND.227/KEYNOTE-483 trial identifies a statistically significant survival benefit with pembrolizumab and chemotherapy vs chemotherapy alone in the first-line setting for patients with unresectable advanced or metastatic malignant pleural mesothelioma.
Treatment with pembrolizumab (Keytruda) and chemotherapy in the first line 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 CCTG IND.227/KEYNOTE-483 study (NCT02784171).
The combination’s safety profile appeared consistent with previous findings. Results from the study are due to read out at an upcoming medical meeting and will be discussed with global regulatory authorities.
“Malignant pleural mesothelioma is a rapidly progressing cancer that develops in the lining of the lungs and has a poor prognosis,” Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said in the press release. “Patients are in need of new treatments that can improve survival outcomes, and these positive results support the potential of [pembrolizumab] in combination with chemotherapy as a first-line treatment for patients with the most common form of malignant mesothelioma.”
The randomized, open-label, phase 3 part of the CCTG IND.227/KEYNOTE-483 study enrolled a total of 440 patients who were randomly assigned to receive either 200 mg of pembrolizumab every 3 weeks for up to 35 cycles plus 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin every 3 weeks for 6 cycles or the chemotherapy backbone alone; substitution with carboplatin was allowed.
The study’s primary end points were OS and progression-free survival, with secondary end points including objective response rate by blinded independent central review, safety, and quality of life.
To be included in the trial, patients were required to have histologically confirmed malignant pleural mesothelioma incurable with standard therapies and be eligible for treatment with standard chemotherapy with no contraindications. Additional inclusion criteria included the presence of radiologically documented disease, being age 18 and older, having an ECOG performance status of 0 or 1, and having all radiology studies within 21 days of study registration.
Patients who were diagnosed with an immunodeficiency or who require systemic steroid therapy, who have active autoimmune disease requiring systemic treatment, or who have not received a live vaccine within 30 days of starting therapy were not eligible for enrollment. Additional exclusion criteria included active central nervous system metastases, having untreated and/or uncontrolled cardiovascular conditions, a history of other malignancies, or a history of allergic reactions to compounds similar to pembrolizumab or the chemotherapy agents included in the study.
KEYTRUDA® (pembrolizumab) plus chemotherapy significantly improved overall survival versus chemotherapy alone as first-line treatment for advanced malignant pleural mesothelioma. News release. Merck. March 10, 2023. Accessed March 10, 2023. http://bit.ly/4240463