The phase 2/3 KEYNOTE-483 trial of pembrolizumab plus chemotherapy for patients with mesothelioma elicited improvements in overall survival and showed consistent safety with previously reported data.
The frontline combination of pembrolizumab (Keytruda) and chemotherapy led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs chemotherapy alone, meeting the primary end point of the phase 2/3 KEYNOTE-483 trial (NCT02784171) in patients with unresectable advanced or metastatic malignant pleural mesothelioma.1
The safety profile of the combination was also consistent with previously reported data from studies of pembrolizumab plus chemotherapy. Additional results from the phase 2/3 KEYNOTE-483 trial will be presented at an upcoming medical meeting and shared with regulatory authorities.
“Malignant pleural mesothelioma is a rapidly progressing 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, in a 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.”
Malignant mesothelioma is a type of cancer that develops in the linings of some parts of the body, including the chest, abdomen, heart, and testicles. Pleural mesothelioma develops in the lining of the lungs and makes up approximately 75% of all cases of malignant mesothelioma.
KEYNOTE-483 is a randomized, open-label trial which included 440 patients who were randomized in a 1:1 fashion to receive either 200 mg of pembrolizumab every 3 weeks for up to 35 cycles in combination with 500 mg/m2 of pemetrexed every 3 weeks for 6 cycles and 75 mg/m2 of cisplatin every 3 weeks for 6 cycles, or pemetrexed plus cisplatin alone. Notably, carboplatin substitution for cisplatin was also permitted.
Those enrolled in the trial were patients aged at least 18 years or older and who had a histologically confirmed unresectable advanced and/or metastatic malignant pleural mesothelioma.2 Patients must have been eligible to receive standard chemotherapy with pemetrexed and cisplatin, had an ECOG performance status of 0 or 1, had no contraindications to standard chemotherapy, were incurable with use of standard therapies.
Patients may have had prior radiation at least 28 days prior to registration. However, radiation to the thorax was not permitted unless clear disease progression was demonstrated. Previous major surgery was also permitted at least 28 days prior to registration.
The primary end point of the study was OS along with secondary end points of blinded independent central review–assessed progression-free survival and objective response rate per RECIST v1.1 criteria modified for mesothelioma. Investigators also evaluated safety and quality of life.1
“There have been few treatment advances for patients with malignant pleural mesothelioma, which can be challenging to treat through surgery and radiation alone,” said Quincy Chu, MD, FRCP, study chair of KEYNOTE-483, in a press release. “The results from the trial have the potential to make a difference for patients with this disease who have had limited treatment options available to them.”