First-line treatment with the high-affinity, highly potent PD-1 inhibitor cemiplimab-rwlc (Libtayo) significantly improved overall survival (OS) and progression-free survival (PFS) compared with standard platinum-based chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) and PD ligand 1 (PD-L1) expression on at least 50% of tumor cells. The results of the second preplanned interim analysis of the phase 3 EMPOWER-Lung 1 clinical trial were presented at the 2020 virtual meeting of the European Society for Medical Oncology (ESMO).
“The EMPOWER-Lung 1 study met its primary and secondary end points. 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 investigator Ahmet Sezer, MD, Department of Medical Oncology, Başkent University, Adana, Turkey.
“The EMPOWER-Lung 1 trial is a real-world symphony,” commented invited discussant Roy S. Herbst, MD, PhD, Chief, Medical Oncology, Yale Cancer Center, New Haven, CT. “This is a trial done late in the game with an approved drug, and it included a more real-world population than other trials of PD-1/PD-L1 inhibitors. Everyone had to be a smoker, and even more significantly, patients were allowed to have stable brain metastasis. This is what we see in the real world,” Dr Herbst added.
In the intent-to-treat (ITT) population, the median OS was not reached in the cemiplimab group versus 14.2 months in the chemotherapy group (P = .0002). In the ITT population with PD-L1 ≥50%, at a median follow-up of 10.8 months, the median OS was not reached in the cemiplimab group versus 14.3 months in the chemotherapy group (P = .0002). This translated to a 43% reduction in mortality risk with the PD-1 inhibitor versus standard chemotherapy.
The median PFS was 8.2 months with cemiplimab versus 5.7 months with the platinum doublet chemotherapy, accounting for a significant 46% reduction in risk for disease progression or death with cemiplimab versus chemotherapy (P <.0001).
Cemiplimab is currently approved by the FDA for the treatment of patients with advanced cutaneous squamous-cell carcinoma. Phase 1 and 2 studies in NSCLC and other solid tumors suggest that cemiplimab has antitumor activity and a safety profile similar to that of other PD-1 inhibitors.
The EMPOWER-Lung 1 trial enrolled treatment-naïve patients with advanced NSCLC and no targetable EGFR, ALK, or ROS1 mutations. However, patients with clinically treated stable central nervous system metastases were eligible for the study.
The study randomized 710 patients in a 1:1 ratio to cemiplimab 350 mg intravenously every 3 weeks or to 4 to 6 cycles of the investigator’s choice of chemotherapy. Treatment was continued until progressive disease or for up to 2 years. The patients in the cemiplimab arm who had progressive disease were allowed to continue to receive cemiplimab plus 4 cycles of chemotherapy; those in the chemotherapy arm could cross over to cemiplimab therapy when their disease progressed.
PD-L1 testing was performed with the 22C3 pharmDx assay. The ITT population with high PD-L1 expression comprised 563 patients with PD-L1 expression ≥50%; they too, were randomized in a 1:1 ratio to cemiplimab or to chemotherapy.
The baseline characteristics were well-balanced between the treatment arms in the overall ITT population and the PD-L1 ≥50% ITT population.
In the PD-L1 ≥50% ITT population, cemiplimab had OS and PFS superior to chemotherapy. At 12 months, the OS rate was 72.4% in patients receiving cemiplimab compared with 53.9% in those receiving chemotherapy. The 24-month survival rates were 50.4% and 27.2%, respectively. The 12-month PFS rates were 40.7% and 7.1%, respectively; the 18-month PFS rate was 27.8% in the cemiplimab arm and was not evaluable in the chemotherapy arm.
Cemiplimab was also superior to chemotherapy in the overall ITT population. At a median follow-up of 13.1 months, the median OS was 22.1 months with cemiplimab versus 55.7% with chemotherapy (P = .0002). The 12-month OS rates were 70.3% and 55.7%, respectively; the 24-month OS rates were 48.6% and 29.7%, respectively. The median PFS was 6.2 months with cemiplimab and 5.6 months with chemotherapy (P <.0001). The 12-month PFS rates were 37.8% and 7.2%, respectively; the 18-month PFS rates were 28% and 3.9%, respectively.
The survival benefit of cemiplimab was evident across all subgroups, except the Asian patients.
Higher PD-L1 expression was correlated with an improved response to cemiplimab but not to chemotherapy, Dr Sezer explained. Regardless of PD-L1 expression level, the PFS and OS curves favored cemiplimab.
Health-related quality of life was maintained in the cemiplimab arm, but deteriorated in the chemotherapy arm, according to the Global Health Status/Health-Related Quality of Life assay.
“The quality of life data are impressive [with cemiplimab]. This becomes even more important as you treat patients for longer periods of time,” Dr Herbst noted.
On October 29, 2020, the FDA granted cemiplimab a priority review for the treatment of patients with advanced NSCLC and PD-L1 expression ≥50%.
Grade ≥3 treatment-emergent adverse events were reported in 37.2% of the patients in the cemiplimab arm and 48.5% of the patients in the chemotherapy arm. Grade ≥3 treatment-related adverse events occurred in 14.1% of the patients in the cemiplimab arm and 39.2% of the patients in the chemotherapy arm. Fatal adverse events occurred in 9% of the patients who received cemiplimab and in 2% of those who received 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 chemotherapy,” Dr Sezer said.