First-line Cemiplimab Plus Chemo Wins Approval in Canada for Advanced NSCLC

Health Canada has approved the combination of cemiplimab-rwlc (Libtayo) and platinum-based chemotherapy for the first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 aberrations who are not candidates for definitive chemoradiation.¹

The regulatory decision was supported by data from the phase 3 EMPOWER-Lung 3 trial (Study 16113; NCT03409614), which showed that cemiplimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in overall survival (OS) vs placebo plus chemotherapy (HR, 0.71; 95% CI, 0.53-0.93; 2-sided P = .0140). Patients treated in the cemiplimab arm (n = 312) experienced a median OS of 21.9 months (95% CI, 15.5-not evaluable) compared with 13.0 months (95% CI, 11.9-16.1) for those in the placebo arm (n = 154).²

“The approval of this new indication of [cemiplimab] highlights continued progress in first-line treatment options for people impacted by advanced lung cancer in Canada,” Barb Melosky, MD, FRCPC, clinical professor of medicine at the University of British Columbia, stated in a news release. “The phase 3 EMPOWER-Lung 3 trial showed significant improvements across primary and key secondary end points, including OS in the cemiplimab plus chemotherapy arm.”

In November 2022, the FDA approved cemiplimab in combination with platinum-based chemotherapy for the treatment of adult patients with advanced NSCLC with no EGFR, ALK, or ROS1 aberrations, based on data from EMPOWER-Lung 3.³

The randomized, multicenter, double-blind, placebo-controlled trial enrolled patients with locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation, or patients with metastatic NSCLC who had not previously received systemic treatment for metastatic disease. Patients were eligible regardless of tumor PD-L1 expression status.²

Those with EGFR, ALK, or ROS1 genomic tumor aberrations were excluded. Other key exclusion criteria included a medical condition that required systemic immunosuppression, or an ongoing or recent autoimmune disease requiring systemic therapy. Patients with a history of brain metastases were eligible if they were previously treated and returned to neurological baseline for at least 2 weeks prior to randomization.

Patients were randomly assigned 2:1 to receive 350 mg of intravenous cemiplimab or matching placebo once every 3 weeks for 108 weeks plus platinum-based chemotherapy every 3 weeks for 4 cycles. Platinum-based chemotherapy consisted of carboplatin area under the curve (AUC) 5 or 6 and 200 mg/m² of paclitaxel; 75 mg/m² of cisplatin and 200 mg/m² of paclitaxel; carboplatin AUC 5 or 6 and 500 mg/m² of pemetrexed; or 75 mg/m² of cisplatin and 500 mg/m² of pemetrexed.

OS served as the trial’s primary end point. Key secondary end points included progression-free survival (PFS) and overall response rate (ORR).

Additional data showed that patients in the cemiplimab arm achieved a median PFS of 8.2 months (95% CI, 6.4-9.3) compared with 5.0 months (95% CI, 4.3-6.2) for those in the placebo arm (HR, 0.56; 95% CI, 0.44-0.70; P < .0001).

The ORR was 43% (95% CI, 38%-49%) in the experimental arm vs 23% (95% CI, 16%-30%) in the control arm. The complete response and partial response (PR) rates in the cemiplimab arm were 2.6% and 41%, respectively. All responders in the placebo arm experienced a PR. The median duration of response was 15.6 months (range, 1.7-18.7+) in the experimental arm vs 7.3 months (range, 1.8-18.8+) in the control arm.

Regarding safety, serious adverse effects (AEs) occurred in 25% of patients treated with cemiplimab plus chemotherapy. The most common serious AEs reported in at least 2% of patients included pneumonia, anemia, and neutropenia.

Six percent of patients who received cemiplimab plus chemotherapy had fatal reactions, including death not otherwise specified (2.9%), sudden death (1.0%), acute hepatitis (0.3%), acute respiratory distress syndrome (0.3%), mesenteric artery thrombosis (0.3%), pneumonia (0.3%), pneumonitis (0.3%), and pulmonary hemorrhage (0.3%).

The most common any-grade AEs that occurred in at least 15% of patients included alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite. The most common grade 3/4 laboratory abnormalities were anemia, neutropenia, lymphopenia, leukopenia, hyponatremia, thrombocytopenia, hyperglycemia, hypophosphatemia, increased alanine aminotransferase (ALT), hypocalcemia, hyperkalemia, hypermagnesemia, hypokalemia, and increased creatinine.

Additionally, 33% of patients needed a dose interruption of cemiplimab due to AEs. AEs that led to interruptions in at least 2% of patients included anemia, pneumonia, neutropenia, thrombocytopenia, fatigue, COVID-19, and pyrexia.

AEs leading to permanent discontinuation of treatment in at least 2 patients included increased ALT and anemia.

References

1. Libtayo (cemiplimab) in combination with chemotherapy now approved in Canada for the first-line treatment of advanced non-small cell lung cancer. News release. Sanofi Canada. May 1, 2023. Accessed May 2, 2023. https://sanoficanada.mediaroom.com/2023
2. Libtayo. Prescribing information. Regeneron Pharmaceuticals, Inc. 2022. Accessed May 2, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761097s014lbl.pdf
3. FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. FDA. November 8, 2022. Accessed May 2, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-combination-platinum-based-chemotherapy-non-small-cell-lung-cancer