Dataset Information

Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer

ABSTRACT:

Objectives

In randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression.

Methods

Patients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring).

Results

In the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction—the most suitable method based on published guidelines and trial characteristics—produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction.

Conclusions

After adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.

SUBMITTER: Feliciano J

PROVIDER: S-EPMC10110970 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn the EMPOWER-Lung 1 trial (ClinicalTrials.gov, NCT03088540), cemiplimab conferred longer survival than platinum-doublet chemotherapy for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. Patient-reported outcomes were evaluated among trial participants.MethodsAdults with NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. At baseline and day 1 of each treatment cycle, patients were administered the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Lung Cancer Module (QLQ-LC13) questionnaires. Mixed-model repeated measures analysis estimated overall change from baseline for PD-L1 ≥50% and intention-to-treat populations. Kaplan-Meier analysis estimated time to definitive deterioration.ResultsIn PD-L1 ≥50% patients (cemiplimab, n = 283; chemotherapy, n = 280), baseline QLQ-C30 and QLQ-LC13 scores showed moderate-to-high functioning and low symptom burden. Change from baseline favored cemiplimab on global health status/quality of life (GHS/QOL), functioning, and most symptom scales. Risk of definitive deterioration across functioning scales was reduced versus chemotherapy; hazard ratios were 0.48 (95% CI, 0.32-0.71) to 0.63 (95% CI, 0.41-0.96). Cemiplimab showed lower risk of definitive deterioration for disease-related (dyspnea, cough, pain in chest, pain in other body parts, fatigue) and treatment-related symptoms (peripheral neuropathy, alopecia, nausea/vomiting, appetite loss, constipation, diarrhea) (nominal p < .05). Results were similar in the intention-to-treat population.ConclusionsResults support cemiplimab for first-line therapy of advanced NSCLC from the patient's perspective. Improved survival is accompanied by improvements versus platinum-doublet chemotherapy in GHS/QOL and functioning and reduction in symptom burden.

Project description:Background: The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.) PCT as the first-line treatment for patients with advanced NSCLC from the perspective of the Chinese healthcare system. Methods: We constructed a Markov model to evaluate the cost-effectiveness of CCT as the first-line treatment for patients with advanced NSCLC. The transition probabilities were extracted from the survival data of the EMPOWER-LUNG 3 trial. The drugs' costs were referred from national tender prices, while other model input parameters were derived from the EMPOWER-LUNG 3 trial and published literature. The outcome parameters mainly included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model outcomes. Results: Compared to PCT, in the CCT regimen, an additional $79,667 was spent in terms of the total cost and with an additional 0.31 QALYs, resulting in an ICER value of $253,148/QALY. Sensitivity analysis indicated that the hazard ratio (HR) of OS, the cost of cemiplimab (100 mg), and the HR of PFS, all significantly impacted the model's results. The probability of CCT (vs. PCT) being cost-effective was 0% at a willingness-to-pay threshold of $38,201/QALYs in China. The scenario analysis showed that when the price of cemiplimab was reduced to less than $184.09/100 mg, the CCT regimen could be considered cost-effective as the first-line treatment for patients with advanced NSCLC compared to the PCT. Conclusion: In China, the CCT was not cost-effective as the first-line treatment for patients with advanced NSCLC.