Cemiplimab With or Without Chemotherapy Provides Long-Term Clinical Benefit in Locally Advanced NSCLC

First-line cemiplimab (Libtayo) monotherapy or in combination with platinum-based chemotherapy conferred long-term clinical benefit to patients with unresectable, locally advanced non–­small cell lung cancer (NSCLC) who were ineligible for concurrent chemoradiation, according to a post-hoc analysis presented at the 2023 European Lung Cancer Congress.¹

The analysis compared long-term survival data from patients in the EMPOWER-Lung 1 (NCT03088540) and EMPOWER-Lung 3 (NCT03409614) studies that looked at the use of cemiplimab alone and with chemotherapy, respectively. In the exploratory analysis, researchers looked at the subgroup of patients with locally advanced NSCLC who made up approximately 15% of the patient population as the trial looked at a broad set of patients with either squamous or nonsquamous NSCLC. From the EMPOWER-Lung 1 study, 87 out of 565 patients had locally advanced NSCLC compared with 69 out of 466 patients in the EMPOWER-Lung 3 study.

At a 35.7 month follow-up of the EMPOWER-Lung 1 cohort, researchers saw a median overall survival (OS) of 26.1 months (95% CI, 17.1-36.6) for patients on cemiplimab compared with a median OS of 13.9 months (95% CI, 9.6-27.0) in the chemotherapy arm (HR, 0.67; 95% CI, 0.38-1.17, P = .1532). In comparison, at a 29.0 month follow-up of the second part of the EMPOWER-Lung 3 study, the median OS of patients on cemiplimab and chemotherapy was 24.1 months (95% CI, 16.5-NE) compared with 13.8 months (95% CI, 10.3-24.8) for patients on placebo and chemotherapy (HR, 0.50; 95% CI, 0.27-0.95, P = .0293). Moreover, at 24 months in the EMPOWER-Lung 1 trial, researchers observed a 56.3% OS rate vs 36.0% in the comparator arm, whereas in the EMPOWER-Lung 3 study they confirmed a 51.8% OS rate for patients treated with cemiplimab vs 34.6% in the comparator arm, according to Ewa Kalinka, MD, PhD, who presented these data at the 2023 conference.

Progression-free survival (PFS) results also remained favoring patients treated with cemiplimab. In the EMPOWER-Lung 1 study, those treated with the immunotherapy had a median PFS of 8.1 months (95% CI, 4.2-14.5) compared with 6.2 months (95% CI, 4.6-6.4) for patients on chemotherapy (HR, 0.56; 95% CI, 0.34-0.95, P = .0286). Moreover, in the EMPOWER-Lung 3 study, a median PFS of 12.5 months (95% CI, 8.2-19.5) was seen for patients on the combination therapy compared with a median of 6.2 months (95% CI, 4.3-6.4) for patients on placebo and chemotherapy (HR, 0.34; 95% CI, 0.19-0.61, P = .0002).

According to Kalinka, an oncologist in the Department of Oncology, Instytut Centrum Zdrowia Matki Polki in Poland, they observed an important milestone for these patients with locally advanced NSCLC as the objective response rate (ORR) favored patients treated with immunotherapy. ORR in the EMPOWER-Lung 1 trial was 48.9% for patients on cemiplimab with 4.4% of those response being complete responses (CR) and 44.4% of those being partial response (PR), whereas patients on chemotherapy had a 31% ORR with 2.4% being CRs and 28.6% being PRs. Treatment with cemiplimab and chemotherapy in the EMPOWER-Lung 3 trial showed 8.9% of patients had a CR with an ORR of 57.8% while there were no CRs in the placebo arm with just a 29.2% ORR.

Duration of response (DOR) was also discussed, but researchers could only estimate it. In EMPOWER-Lung 1, a median DOR of 18.8 months was seen in 22 patients on cemiplimab alone compared with a median DOR of 6.2 months for 13 patients on chemotherapy alone. In EMPOWER-Lung 2, 26 patients in the combination arm had a DOR of 27.8 months vs 4.2 months for 7 patients on placebo and chemotherapy.

Both trials used 350 mg of cemiplimab given intravenously once every 3 weeks until progression of disease or until 108 weeks. A key difference between the studies was that in the EMPOWER-Lung 1 study, investigators compared the immunotherapy to 4-6 cycles of the investigators’ choice of chemotherapy and looked only at patients with a PD-L1 expression of 50% or more. In comparison, the EMPOWER-Lung 3 study allowed for patients with any level of PD-L1 expression and added 4 cycles of platinum doublet chemotherapy to cemiplimab.

No new safety signals were observed in the analysis, with the most common adverse events (AEs) on cemiplimab in the EMPOWER-Lung 1 study being arthralgia (15.6%), back pain (15.6%), anemia (13.3%), and pneumonia (13.3%). With the addition of chemotherapy in the EMPOWER-Lung 3 study along with arthralgia (15.6%), anemia (40%), and fatigue (13.3%), other common AEs included alopecia (40%), nausea (31.1%), neutropenia (20%), increased alanine aminotransferase (20%), and peripheral sensory neuropathy (20%).

“The long-term follow-up data from both trials continues to demonstrate the clinical benefit of first-line cemiplimab as monotherapy, or in combination with platinum-based chemotherapy in the treatment of patients with locally advanced NSCLC who are not candidates for concurrent chemoradiation,” concluded Kalinka. “The safety profile...doesn't give us any new signals from what we know, and the data highlight cemiplimab addresses an unmet clinical need for this subset of patients.”

Reference

Kalinka E, Bondarenko I, Gogishvili M, et al. First-line cemiplimab for locally advanced non-small cell lung cancer: Updated subgroup analyses from EMPOWER-Lung 1 and EMPOWER-Lung 3. Presented at: 2023 European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Abstract 114MO.