Dataset Information

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.

ABSTRACT:

Background

For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010-2020.

Methods

Relevant RCTs were identified by searching databases and conference proceedings as per ISPOR, NICE, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR) and safety/tolerability. Fixed-effect models were used due to limited evidence. Various sensitivity analyses were conducted to validate the base case analyses.

Results

The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an incompatible PD-L1 assay (SP142) was used for patient selection. For first-line advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 (0.50-0.86), 1-12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04-2.62)], and comparable OS [HR (95% CrI): 0.77 (0.54-1.10), 1-12 months] versus pembrolizumab. There was no evidence of differences between cemiplimab and pembrolizumab for Grade 3-5 adverse events (AEs) [OR (95% CrI): 1.47 (0.83-2.60)], immune-mediated AEs [1.75 (0.33-7.49)], and all-cause discontinuation due to AEs [1.21 (0.58-2.61)].

Conclusions

Considering the limitations of indirect treatment comparisons, in patients with advanced NSCLC and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability versus pembrolizumab.

SUBMITTER: Freemantle N

PROVIDER: S-EPMC9210099 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.

Freemantle Nick N Xu Yingxin Y Wilson Florence R FR Guyot Patricia P Chen Chieh-I CI Keeping Sam S Konidaris Gerasimos G Chan Keith K Kuznik Andreas A Atsou Kokuvi K Glowienka Emily E Pouliot Jean-Francois JF Gullo Giuseppe G Rietschel Petra P

Therapeutic advances in medical oncology 20220616

<h4>Background</h4>For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) <i>versus</i> chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic lit ...[more]

PMID: 35747163

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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:Objective: Three immune checkpoint inhibitors (ICIs), pembrolizumab, atezolizumab and cemiplimab, have been successively approved as first-line treatments for advanced non-small-cell lung cancer (NSCLC) patients with programmed cell death ligand 1(PD-L1) expression of at least 50%. This study was designed to compare the cost-effectiveness of these three novel therapies in this patient population. Material and Methods: Using Markov model and network meta-analysis, we conducted separate cost-effectiveness analyses for cemiplimab, pembrolizumab and atezolizumab among advanced NSCLC patients with PD-L1 of at least 50% from the United States health care sector perspective. Health states included progression-free survival, progressive disease, end-stage disease, and death. Clinical efficacy and safety data were derived from phase III clinical trials and health state utilities and costs data were collected from published resources. Two scenario analyses were conducted to assess the impact of varying subsequent anticancer therapies on the cost-effectiveness of these 3 ICIs and cost-effectiveness of pembrolizumab combined with chemotherapy versus these 3 first-line ICI monotherapies. Results: In base case analysis, cemiplimab compared with pembrolizumab was associated with a gain of 0.44 quality-adjusted life-years (QALYs) and an increased cost of $23,084, resulting in an incremental cost-effectiveness ratio (ICER) of $52,998/QALY; cemiplimab compared with atezolizumab was associated with a gain of 0.13 QALYs and a decreased cost of $104,642, resulting in its dominance of atezolizumab. The first scenario analysis yielded similar results as our base case analysis. The second scenario analysis founded the ICERs for pembrolizumab plus chemotherapy were $393,359/QALY, $190,994/QALY and $33,230/QALY, respectively, compared with cemiplimab, pembrolizumab and atezolizumab. Conclusion: For advanced NSCLC patients with PD-L1 of at least 50%, cemiplimab was a cost-effective option compared with pembrolizumab and a dominant alternative against atezolizumab. Our scenario analysis results supported the cemiplimab plus chemotherapy as a second-line therapy and suggested an extended QALY but overwhelming cost linking to pembrolizumab plus chemotherapy.

Project description:BackgroundThis study investigated real-world time on treatment (rwToT) and overall survival (OS) for patients with metastatic non-small cell lung cancer (mNSCLC) who initiated first-line (1L) pembrolizumab monotherapy. We also explored discontinuation reasons and subsequent treatments, stratified by number of cycles among those who completed ≥17 cycles of 1L pembrolizumab.MethodsPatients with mNSCLC without actionable genetic aberrations, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and unknown, and PD-L1 TPS ≥ 50% starting 1L pembrolizumab monotherapy between 24-Oct-2016 and 31-Dec-2018 within The US Oncology Network were identified retrospectively and evaluated using structured data, with a data cutoff of 30-Sep-2021. Patient characteristics and disposition were summarized using descriptive statistics. OS and rwToT were evaluated using Kaplan-Meier method for all ECOG PS and PS 0-1. A subgroup of patients who completed ≥17 cycles were evaluated using supplemental chart review data to discern reasons for discontinuation.ResultsOf the 505 patients with mNSCLC with PD-L1 TPS ≥50%, 61% had ECOG PS 0-1, 23% had ECOG PS 2, and 65% had nonsquamous histology. Median rwToT and OS of pembrolizumab were 7.0 (95% CI, 6.0-8.4) months and 24.5 (95% CI, 20.1-29.3) months, respectively. In the subgroup with ECOG PS 0-1, they were 7.6 months (95% CI, 6.2-9.2) and 28.8 months (95% CI, 22.4-37.5), respectively. Of the 103 patients who completed ≥17 cycles, 57 (55.3%) patients received 17 - 34 cycles and 46 (44.7%) patients received ≥35 cycles. Approximately 7.7% of the study population received pembrolizumab beyond 35 cycles. Most common reasons for discontinuation were disease progression (38.6%) and toxicity (19.3%) among patients who received 17-34 cycles of pembrolizumab, and disease progression (13.0%) and completion of therapy (10.9%) among patients who received ≥35 cycles.ConclusionConsistent with findings from KEYNOTE-024 and other real-world studies, this study demonstrates the long-term effectiveness of pembrolizumab monotherapy as 1L treatment for mNSCLC with PD-L1 TPS ≥50%. Among patients who completed ≥17 cycles, nearly half completed ≥35 cycles. Disease progression and toxicity were the most common reasons for discontinuation among patients who received 17-34 cycles of pembrolizumab. Reasons for discontinuation beyond 35 cycles need further exploration.

Dataset Information

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.

Background

Methods

Results

Conclusions

Publications

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.

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