First-line treatment with cemiplimab-rwlc monotherapy improved overall survival, progression-free survival, and objective response rates compared with chemotherapy in patients with advanced non–small cell lung cancer (NSCLC) with PD-L1 expression of at least 50% and clinically stable treated brain metastases, according to a post hoc subgroup analysis of the phase III EMPOWER-Lung 1 trial.1 These results of the substudy mirror the results in all patients included in the EMPOWER-Lung 1 trial. Cemiplimab is a monoclonal antibody directed against PD-1 and considered a new option for the treatment of NSCLC with PD-L1 ≥ 50%.
“In this substudy of EMPOWER-Lung 1, cemiplimab provided durable benefits in patients with treated clinically stable brain metastases. Cemiplimab monotherapy represents a suitable option for this subgroup of patients,” stated the first author of this poster presentation, Mustafa Özgüroglu, MD, of Istanbul University-Cerrahpasa, Turkey.
“In this substudy of EMPOWER-Lung 1, cemiplimab provided durable benefits in patients with treated clinically stable brain metastases.”— Mustafa Özgüroglu, MD
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Approximately 10% of all patients with newly diagnosed NSCLC have brain metastases, as do 26% of those with stage IV disease at diagnosis. The prognosis for these patients is generally poor. Whole-brain radiotherapy is often used to treat these patients, but responses are not durable, and patients with a large burden of disease typically cannot delay receiving systemic treatment to undergo radiotherapy.
In the overall results of the EMPOWER-Lung 1 trial, first-line cemiplimab monotherapy was superior to investigator’s choice of chemotherapy in achieving overall survival, progression-free survival, and objective response rates, as well as having a longer duration of response in this group of patients. The study included 710 patients with advanced NSCLC of whom 563 had PD-L1 expression ≥ 50%. Patients were randomly assigned to receive cemiplimab monotherapy intravenously at 350 mg every 3 weeks with treatment continued until disease progression vs four to six cycles of investigator’s choice of chemotherapy. At disease progression, patients randomly assigned to cemiplimab could continue to receive the drug along with four cycles of chemotherapy and those randomly assigned to chemotherapy were given the option to cross over to cemiplimab.
The positive results of EMPOWER-Lung 1 led to the inclusion of cemiplimab in the updated National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (version 4.2021) for NSCLC as a category 1 preferred first-line treatment option for patients with NSCLC and PD-L1 expression ≥ 50%.
“Historically, patients with brain metastases have been underrepresented in clinical trials of NSCLC. However, EMPOWER-Lung 1 included a notable proportion of patients with brain metastases,” Dr. Özgüroglu said.
The post hoc EMPOWER-Lung 1 substudy focused on a total of 68 patients (12.1% of the study population) with adequately treated clinically stable brain metastases at the time of randomization. Patients received standard whole-brain radiation therapy and were stable 14 days before randomization. A total of 34 patients were randomly assigned to receive cemiplimab and 34, to investigator’s choice of chemotherapy. Brain imaging was performed at regular intervals.
At baseline, the median patient age was about 60. There were more men in the cemiplimab group (33 vs 29 in the chemotherapy group) and more patients with an Eastern Cooperative Oncology Group performance status of 0 (10 vs 5, respectively). Nonsquamous histology was documented in 85.3% of the cemiplimab group vs 76.5% of the chemotherapy group.
The median duration of follow-up was about 9.2 weeks for both arms of the analysis. Estimated overall survival was 18.7 months with cemiplimab vs 11.7 months with investigator’s choice of chemotherapy (P = .0091), representing an estimated improvement of 83% for cemiplimab. Estimated progression-free survival was 10.4 months vs 5.3 months with chemotherapy (P = .0231), representing an estimated 55% improvement with cemiplimab. The objective response rate was 41.2% for cemiplimab vs 8.8% for chemotherapy.
Cemiplimab reduced the risk of brain metastases progression-free survival and death by 72% vs chemotherapy, according to a Kaplan-Meier estimation. Intracranial disease progression was observed in two cemiplimab-treated patients (5.9%) vs four chemotherapy-treated patients (11.8%). Intracranial disease progression due to a new tumor occurred in one cemiplimab-treated patient (2.9%) vs four chemotherapy-treated patients (11.8 %). Intracranial disease progression due to an existing tumor occurred in two patients (5.9%) vs one patient (2.9%), respectively.
“These findings are limited to a post hoc analysis and should be considered exploratory,” wrote the authors.
DISCLOSURE: The study was funded by Regeneron. Dr. Özgüroglu has received honoraria from Astellas Pharma and Novartis; has received institutional honoraria from Janssen Oncology; has served as a consultant or advisor to AstraZeneca and MSD Oncology; has participated in a speakers bureau for AstraZeneca; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca.
1. Özgüroglu M, Sezer A, Kilickap S, et al: Cempilimab monotherapy as first-line treatment of patients with brain metastastases from advanced non-small cell lung cancer with PD-L1 ≥ 50%: EMPOWER-Lung-1 subgroup analysis. 2021 ASCO Annual Meeting. Abstract 9085. Presented June 4, 2021.