First-line treatment with the combination of pembrolizumab and chemotherapy generated a statistically significant and clinically meaningful improvement in overall survival compared with chemotherapy alone in patients with unresectable advanced or metastatic malignant pleural mesothelioma.
First-line treatment with the combination of pembrolizumab (Keytruda) and chemotherapy generated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with chemotherapy alone in patients with unresectable advanced or metastatic malignant pleural mesothelioma, meeting the primary end point of the phase 2/3 KEYNOTE-483 trial (NCT02784171).1
Safety findings were consistent with data from previously reported studies of pembrolizumab plus chemotherapy. Full results 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,” Eliav Barr, MD, senior vice president, head of Global Clinical Development and chief medical officer at Merck Research Laboratories, stated in a news 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 develops in the linings of certain parts of the body, including the chest, abdomen, heart, and testicles. Pleural mesothelioma accounts for approximately 75% of all cases of malignant mesothelioma.
The randomized, open-label KEYNOTE-483 trial enrolled patients at least 18 years of age with histologically confirmed unresectable advanced and/or metastatic malignant pleural mesothelioma who were eligible to receive standard chemotherapy with pemetrexed and cisplatin, had no contraindications to standard chemotherapy, were incurable by standard therapies, and had an ECOG performance status of 0 or 1.2
No prior chemotherapy for any stage of advanced/metastatic disease was permitted. Those who received previous neoadjuvant/adjuvant cisplatin-based systemic chemotherapy needed to be at least 12 months removed from their last dose of chemotherapy. Patients were not allowed to have prior targeted small molecule therapy, viral therapies, biologic therapies, or angiogenesis inhibitors for advanced/metastatic disease, or immunotherapy in any setting.
Radiation was permitted at least 28 days prior to registration, but radiation to the thorax was not permitted unless clear disease progression had been demonstrated. Surgery was permitted at least 28 days prior to registration.
Patients with active central nervous system metastases and/or carcinomatous meningitis were excluded.
In the phase 3 trial, investigators randomly assigned 440 patients in a 1:1 fashion to 200 mg of pembrolizumab every 3 weeks for up to 35 cycles in combination with 500 mg/m2 of pemetrexed every 3 weeks for six cycles and 75 mg/m2 of cisplatin every 3 weeks for 6 cycles, or pemetrexed plus cisplatin alone. Notably, carboplatin substitution for cisplatin was permitted.
Along with the primary end point of OS, secondary end points included blinded independent central review–assessed progression-free survival and objective response rate per RECIST v1.1 criteria modified for mesothelioma, as well as 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,” Quincy Chu, MD, FRCP, study chair of KEYNOTE-483, stated in a news 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.”