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.

Background

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.

Study Details

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.

Safety

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.

REFERENCE

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.