1. Nalley, Catlin

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Treatment with cemiplimab plus chemotherapy in the first line demonstrated clinically meaningful and statistically significant improvements in outcomes for patients with advanced non-small cell lung cancer (NSCLC) when compared to chemotherapy alone, according to recently reported data.

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"[Cemiplimab] added to chemotherapy significantly improved patient outcomes, extending median overall survival to 22 months and median progression-free survival to 8 months," said study author Miranda Gogishvili, MD, an oncologist at the High Technology Medical Center University Clinic, in Tbilisi, Georgia, in a statement.


"Exploratory analyses showed that survival improvements were seen across squamous and non-squamous histologies and in patients with reduced daily functioning, with 43 percent of patients having squamous disease and 84 percent having an ECOG 1 performance status," she reported. "Furthermore, in another exploratory analysis, the [cemiplimab] combination helped delay deterioration in patient-reported quality of life and pain symptoms."


Cemiplimab is a high-affinity, fully human anti-PD-1 agent that has demonstrated safety and efficacy in the EMPOWER-Lung 3 study, according to Gogishvili. This treatment is approved as a first-line monotherapy for advanced NSCLC patients whose tumors have high PD-L1 expression (>=50%) and no EGFR, ALK, or ROS1 aberrations.


Findings from the pre-specified second interim analysis (with a data cutoff of June 14, 2021) of EMPOWER-Lung 3 (Part 2) were presented by Gogishvili during the ESMO Congress 2021 (Abstract LBA51).



EMPOWER-Lung 3, a randomized, two-part, Phase III study, examined first-line treatment of patients with advanced (Stage III/IV) squamous or non-squamous NSCLC without actionable mutations. The double-blind Part 2 of the study enrolled patients irrespective of PD-L1 levels and compared clinical activity and safety of cemiplimab in combination with platinum-based chemotherapy, versus placebo plus chemotherapy.


Patients-stratified by PD-L1 expression and histology-were randomized 2:1 to receive either cemiplimab 350 mg once every 3 weeks or placebo once every 3 weeks for 108 weeks (or until disease progression). Patients in both arms also received up to 4 cycles of chemotherapy, followed by mandatory pemetrexed maintenance for non-squamous patients assigned to a pemetrexed-containing regimen, Gogishvili explained.


The primary endpoint of the study was overall survival. Key secondary endpoints included progression-free survival and objective response rate per blinded independent central review.


Study Findings

Overall, the researchers randomized 466 patients to the cemiplimab plus chemotherapy (n=312) or chemotherapy only (n=154) group. Baseline characteristics were generally balanced between both arms, according to Gogishvili.


The median age was 63 (25-84) years. The majority of patients were male (83.9%) and 393 of included patients (84.3%) had an ECOG performance status of 1. When looking at the histology breakdown, 266 patients (57.1%) had non-squamous NSCLC and 200 patients (42.9%) had squamous disease. The researchers reported that 85.2 percent of patients in the study had Stage IV disease.


"At a median follow-up of 16 months cemiplimab plus chemotherapy led to a statistically significant and clinically meaningful improvement in median overall survival (22 months vs. 13 months, HR=0.71)," said Gogishvili, who noted that progression-free survival improved as well among patients receiving cemiplimab (8.2 months vs. 5 months, HR=0.56).


"Objective response rate was also higher in cemiplimab plus chemotherapy at 43 percent, including 2.6 percent complete responses," she noted during her presentation. "Median duration of response [for patients in the cemiplimab arm] was longer (15.6 months vs. 7.3 months)."


The researchers also observed favorable patient-reported outcomes. For instance, cemiplimab plus chemotherapy delayed deterioration in pain symptoms and showed a trend towards delayed deterioration in global health status/quality of life, when compared to chemotherapy, according to the study authors. Pain symptoms were also improved among patients receiving the combination treatment compared to their chemotherapy-only counterparts.


The safety profile for cemiplimab plus chemotherapy was generally consistent with the known profile and no new safety signals were identified. The median duration of exposure was 38.5 weeks for the cemiplimab combination and 21.3 weeks for chemotherapy alone.


Treatment emergent adverse events of any grade were reported in 96 percent of patients undergoing cemiplimab plus chemotherapy and in 94 percent of those receiving placebo plus chemotherapy. Of these events, 5 percent led to discontinuation in the combination arm and 3 percent in the chemotherapy only group. Immune-related adverse events of any grade occurred in 19 percent of patients receiving cemiplimab and 0 percent in the placebo cohort.


Overall, the most common adverse events for both treatment groups were anemia, alopecia, and nausea. The incidence of Grade >=3 adverse events was 44 percent in the cemiplimab plus chemotherapy arm and 31 percent in the placebo plus chemotherapy group. Common Grade >=3 adverse events occurring in 5 percent or more patients included anemia and neutropenia.


Concluding her presentation, Gogishvili noted, "In patients with advanced NSCLC, first-line cemiplimab in combination with chemotherapy demonstrated clinically meaningful and statistically significant improvement in overall survival, progression-free survival, objective response rate, and duration of response versus chemotherapy alone.


"Cemiplimab in combination with chemotherapy demonstrated an acceptable benefit-risk profile, favorable patient-reported outcomes, low rates of adverse events leading to discontinuation, and a safety profile generally consistent with those known for cemiplimab and for platinum-based chemotherapy," she continued.


"Cemiplimab with platinum-doublet chemotherapy is a new first-line treatment option for patients with advanced NSCLC without targetable mutations irrespective of histology and PD-L1 levels," Gogishvili concluded.


Catlin Nalley is a contributing writer.