The European Society for Medical Oncology (ESMO) Virtual Congress 2020 presented several abstracts with good news for patients with lung cancer. Long-term follow-up of immunotherapies showed excellent survival, a promising new ALK inhibitor improved outcomes compared with the standard of care, the first KRAS-targeted drug improved outcomes, and a survival benefit was reported for cemiplimab (a PD-1 inhibitor that is new to lung cancer).
First-line treatment with cemiplimab significantly improved overall and progression-free survival compared with a platinum doublet in advanced non–small lung cancer (NSCLC) with PD-L1 expression of at least 50% of tumor cells. These findings of the second preplanned interim analysis of the phase III EMPOWER-Lung 1 trial were presented at the ESMO Virtual Congress 2020.1
At a median follow-up of 10 months in the PD-L1 ≥ 50% intent-to-treat population, median overall survival was not reached for the cemiplimab arm vs 14.2 months for the control arm (P = .0002). This represented a 43% reduction in the risk of death with the PD-1 inhibitor compared with a former standard of care (platinum doublet). Median progression-free survival was 8.2 months with cemiplimab vs 5.7 months with the platinum doublet, representing a highly significant 46% reduction in the risk of disease progression or death with cemiplimab vs chemotherapy (P < .0001).
“Our data provide the rationale for cemiplimab as a new first-line monotherapy option for patients with advanced NSCLC and PD-L1 expression ≥ 50%.”— Ahmet Sezer, MD
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“The EMPOWER-Lung 1 study met its primary and secondary endpoints. Taken together, our data provide the rationale for cemiplimab as a new first-line monotherapy option for patients with advanced NSCLC and PD-L1 expression ≥ 50%,” stated lead author Ahmet Sezer, MD, of Baskent University, Ankara, Turkey.
PD-1/PD-L1 inhibitors alone or in combination are considered preferred treatment options for patients with advanced NSCLC and no targetable mutations plus PD-L1 expression ≥ 50%. Selection of treatment depends on consideration of risk vs benefit. Options for NSCLC should improve survival and be well tolerated when possible, and cemiplimab represents a monotherapy option with an improved safety profile over that of platinum-based chemotherapy.
Cemiplimab is a high-affinity PD-1 inhibitor approved by the U.S. Food and Drug Administration for the treatment of advanced cutaneous squamous cell carcinoma. Phase I and II studies in NSCLC and other solid tumors showed that cemiplimab had similar antitumor activity and safety profile compared with other PD-1 inhibitors.
Eligible patients for EMPOWER-Lung 1 had treatment-naive advanced NSCLC; PD-L1 expression ≥ 50%; and no targetable EGFR,ALK, or ROS1 mutations. Treated clinically stable central nervous system metastasis was allowed.
EMPOWER-Lung 1 randomly assigned 710 patients 1:1 to receive cemiplimab at 350 mg intravenously every 3 weeks vs four to six cycles of investigator’s choice platinum doublet. Treatment was continued until progressive disease or for up to 2 years. Patients in the cemiplimab arm were allowed to continue the drug plus be treated with four cycles of chemotherapy upon progressive disease; those in the chemotherapy arm who developed progressive disease could cross over to cemiplimab.
PD-L1 Expression ≥ 50%
Patients were tested for PD-L1 status using the 22C3 pharmDx assay. Dr. Sezer explained that the first 235 enrollees had faulty PD-L1 testing and had to be retested. After retesting for PD-L1, 563 patients met the criteria for PD-L1 expression ≥ 50%, and these patients comprised the intent-to-treat population for high PD-L1 expressers; 283 were treated with cemiplimab and 280, with chemotherapy.
Baseline characteristics were well balanced between the treatment arms in both the overall intent-to-treat population and the PD-L1 expression ≥ 50% intent-to-treat population. About 11% had baseline central nervous system metastases, and 16.2% had locally advanced disease.
In the PD-L1 expression ≥ 50% intent-to-treat population overall and progression-free survival analyses, cemiplimab was superior to chemotherapy; 12-month overall survival was 72.4% with cemiplimab vs 53.9% with chemotherapy. The 24-month survival rate was 50.4% vs 27.2%, respectively. In the PD-L1 expression ≥ 50% intent-to-treat population, the 12-month progression-free survival rate was 40.7% vs 7.1%, respectively; the 18-month progression-free survival rate was 27.8% with cemiplimab and was not evaluable with chemotherapy.
Survival and Quality of Life
Cemiplimab was superior to chemotherapy in the overall intent-to-treat population. At a median follow-up of 13.1 months, median overall survival was 22.1 months with cemiplimab vs 14.3 months with chemotherapy (P = .0022). The 12-month overall survival was 70.3% vs 55.7%, respectively; the 24-month overall survival was 48.6% vs 29.7%, respectively. Median progression-free survival was 6.2 months with cemiplimab vs 5.6 months with chemotherapy (P < .0001). The 12-month progression-free survival was 37.8% vs 7.2%, respectively; the 18-month progression-free survival was 28% vs 3.9%, respectively.
Subgroups, with the exception of Asian patients, almost universally benefited from cemiplimab in terms of both overall and progression-free survival. The median time to response to both cemiplimab and chemotherapy in both intent-to-treat analyses was 2.1 months.
Higher PD-L1 expression was correlated with improved response to cemiplimab but not chemotherapy, Dr. Sezer explained. Regardless of the PD-L1 expression level, the progression-free survival and overall survival curves favored cemiplimab.
Health-related quality of life improved in the cemiplimab arm but deteriorated in the chemotherapy arm, as measured by the Global Health Status/Health-Related Quality-of-Life assay. Improvement or deterioration was defined on that assay as at least a 10-point increase or decrease, respectively, from baseline.
The median duration of treatment was 27.3 months with cemiplimab vs 17.7 months with chemotherapy.
Grade 3 or higher treatment-emergent adverse events were reported in 37.2% of the cemiplimab arm and 48.5% of the chemotherapy arm. Grade 3 or higher treatment-related adverse events occurred in 14.1% of the cemiplimab arm and 39.2% of the chemotherapy arm. Fatal adverse events were 9% with cemiplimab and 2% with chemotherapy.
“The safety profile of cemiplimab was consistent with the previously reported profile for cemiplimab and other PD-1/PD-L1 inhibitors in NSCLC and other tumor types. Despite substantially longer exposure to cemiplimab, the safety profile of cemiplimab appears to be better than that of chemotherapy,” Dr. Sezer stated.
DISCLOSURE: The study was funded by Regeneron Pharmaceuticals and Sanofi. Dr. Sezer has received institutional research funding from Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals, and Sanofi.
1. Sezer A, Kilickap S, Gümüs M, et al: EMPOWER-Lung 1: Phase III first-line cemiplimab monotherapy vs platinum-doublet chemotherapy in advanced non-small cell lung cancer with PD-L1 ≥ 50%. ESMO Virtual Congress 2020. Abstract LBA52. Presented September 21, 2020.
Roy S. Herbst, MD, PhD, FACP, FASCO
Invited discussant of the EMPOWER-Lung 1 trial, Roy S. Herbst, MD, PhD, FACP, FASCO, Chief, Medical Oncology, Yale Cancer Center, New Haven, Connecticut, pointed out the tremendous progress that has been made since 2000 in treating NSCLC. “In 2000, median...