First-line cemiplimab monotherapy significantly improved overall survival and progression-free survival compared to chemotherapy among patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 >=50 percent, despite a high crossover rate, according to findings presented at the ESMO Asia Virtual Congress 2020 (Abstract 378MO).
EMPOWER-Lung 1, a multicenter, open-label, global, Phase III study, investigated cemiplimab, an anti-PD-1, in patients with treatment-naive stage IIIB, IIIC, or IV squamous or non-squamous NSCLC with PD-L1 expressed in >=50 percent of tumor cells. The findings suggest that cemiplimab monotherapy is a viable first-line option for this patient population.
Methodology & Findings
This randomized trial compared first-line cemiplimab monotherapy given at 350 mg every 3 weeks with 4-6 cycles of investigator's choice chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression.
Key eligibility criteria included treatment-naive advanced NSCLC; PD-L1 >=50 percent; no EGFR, ALK, or ROS1 mutations; and ECOG PS of 0 or 1. Additionally, patients with treated, clinically stable CNS metastases and controlled hepatitis B or C or HIV were allowed to enroll.
Primary endpoints included overall survival and progression-free survival. Overall response rate, duration of response, HRQoL, and safety were the secondary objectives.
"We enrolled and randomized 710 patients," said study author Ahmet Sezer, MD, Associate Professor of Medical Oncology at Baskent University in Adana, Turkey. "Notably, and as was allowed per protocol, 73.9 percent of patients who progressed on chemotherapy received cemiplimab as a crossover treatment. A total of 31.6 percent of patients who progressed on cemiplimab received extended treatment with additional chemotherapy.
"For the primary endpoints, this presentation will focus on the PD-L1 >=50 percent population, which consists of 563 patients who had PD-L1 testing performed by 22C3 assay per instructions for use. The population was at the request of the FDA to the sponsor," he explained.
The baseline characteristics were well-balanced between the cemiplimab and chemotherapy arms. "Of note, there was a substantial proportion of patients who had brain metastases and locally advanced NSCLC," Sezer highlighted. "These patients have been underrepresented in clinical trials for first-line PD-1/PD-L1 inhibitors."
Among the PD-L1 >=50 percent population, the median overall survival was not reached for cemiplimab. Comparatively, the median overall survival was 14.2 months for patients treated with chemotherapy.
"The 12-month and 24-month overall survival rates were longer for cemiplimab versus chemotherapy," Sezer reported. "Cemiplimab also significantly improved progression-free survival with median 8.2 months versus 5.7 months with chemotherapy. These results were consistent with that observed in the ITT population.
"Response rate was higher for cemiplimab at 39.2 percent compared with 20.4 percent for chemotherapy," he continued. "The median duration of response was 16.7 months for cemiplimab and 6.0 months for chemotherapy."
The researchers conducted an exploratory analysis and discovered that the reduction in tumor volume with cemiplimab was greater with increasing PD-L1 levels, according to Sezer. "Patients with PD-L1 expression levels of 90 percent or more demonstrated the largest reduction in tumor measurement."
Changes from baseline in Global Health Status and HRQoL were also reported. A change of 10 points or more was considered clinically meaningful. "Early and sustained clinically meaningful improvements in health-related quality of life were observed with cemiplimab, but not with chemotherapy," noted Sezer.
In terms of safety, the researchers reported that adverse events leading to deaths were considered related to treatment in 2.5 percent of patients treated with cemiplimab compared to 2 percent of those who underwent chemotherapy.
"Immune-related adverse events occurred in 17.5 percent of patients in the cemiplimab arm and 2.3 percent of patients in chemotherapy arm," Sezer said. "Overall, despite substantially longer exposure to cemiplimab, the safety profile of cemiplimab was consistent with the previous reports of other PD-1/PD-L1 inhibitors."
Concluding his presentation, Sezer noted that the EMPOWER-Lung 1 study met its primary and secondary endpoints. "Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy," he summarized. "The significant improvement in overall survival was achieved despite a high crossover rate of 74 percent.
"Despite substantially longer exposure to cemiplimab, the safety profile and patient-reported quality of life support the positive benefit-risk profile for cemiplimab," Sezer stated. "Our data provides rationale for cemiplimab as the new first-line, monotherapy option for patients with advanced, non-small cell lung cancer with PD-L1 >=50 percent."
Catlin Nalley is a contributing writer.