Dataset Information

Stage as the Sole "Biomarker" for Adjuvant Pembrolizumab in Resected Stage IB to IIIA NSCLC without Considerations for PD-L1 Expression Level, ALK/EGFR Mutational Status, and Prior Adjuvant Chemotherapy per FDA Approval Indications of PEARLS/Keynote-091?

ABSTRACT: One of the most recent advancements in NSCLC was the approval of immunotherapy in the adjuvant setting. Both atezolizumab and pembrolizumab have been approved for the use in early stage NSCLC patients post resection. As it broadens the options for our patients, multiple approvals in the same setting are generally welcomed. However, there were important differences in the two studies that led to the approvals and the data could be confusing. Here we review IMpower010, the study that led to the first approval of atezolizumab in the adjuvant setting with comparison to the Keynote-091 study evaluating pembrolizumab in the adjuvant setting, gaining the most recent FDA approval for adjuvant use in early stage NSCLC.

SUBMITTER: Nagasaka M

PROVIDER: S-EPMC10725831 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Stage as the Sole "Biomarker" for Adjuvant Pembrolizumab in Resected Stage IB to IIIA NSCLC without Considerations for PD-L1 Expression Level, ALK/EGFR Mutational Status, and Prior Adjuvant Chemotherapy per FDA Approval Indications of PEARLS/Keynote-091?

Nagasaka Misako M Ou Saihong Ignatius SI

Lung Cancer (Auckland, N.Z.) 20231212

One of the most recent advancements in NSCLC was the approval of immunotherapy in the adjuvant setting. Both atezolizumab and pembrolizumab have been approved for the use in early stage NSCLC patients post resection. As it broadens the options for our patients, multiple approvals in the same setting are generally welcomed. However, there were important differences in the two studies that led to the approvals and the data could be confusing. Here we review IMpower010, the study that led to the fi ...[more]

PMID: 38111829

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Project description:The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in patients with resected stage IB-IIIA non-small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)-IIIA NSCLC. Upon completing 1-4 cycles of adjuvant cisplatin-based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator-assessed disease-free survival, tested hierarchically first in patients with stage II-IIIA NSCLC whose tumors expressed programmed death-ligand 1 (PD-L1) on ≥1% of tumor cells, then in all randomized patients with stage II-IIIA NSCLC, and finally in the intention-to-treat (ITT) population (stage IB-IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all-randomized stage II-IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD-L1 tumor cells ≥1% stage II-IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease-free survival improvement with atezolizumab vs BSC was observed in the PD-L1 tumor cells ≥1% stage II-IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25-1.08), all-randomized stage II-IIIA (unstratified HR, 0.62; 95% CI, 0.35-1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34-1.10) populations. Atezolizumab-related grade 3/4 adverse events occurred in 16% of patients; no treatment-related grade 5 events occurred. Adjuvant atezolizumab showed disease-free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.

Project description:BackgroundAtezolizumab was first shown to significantly improve progression-free survival (PFS) after platinum-based chemotherapy in early-stage non-small cell lung cancer (NSCLC) in the IMpower010 Phase 3 trial. However, the cost-effectiveness and potential economic impact of atezolizumab treatment in Chinese patients are unknown.MethodsMarkov models were constructed based on follow-up data from the IMpower010 trial and assessed separately in the programmed cell death receptor ligand-1 (PD-L1) tumor cells (TC) ≥ 1% stage II - IIIA group, all stage II - IIIA groups, and the intention-to-treat (ITT) group (stage IB-IIIA). Efficacy and safety data were obtained from the IMpower010 trial, and costs and utility values were derived from the literature and local surveys to estimate their incremental cost-effectiveness ratios (ICERs) compared with willingness-to-pay (WTP) thresholds in scenarios implementing patient assistance programs (PAP) or drug price negotiations. Univariate sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to investigate the stability of the model results.ResultsCompared with best supportive care (BSC), atezolizumab produced an additional 0.45 quality-adjusted life-years (QALYs), 0.04 QALYs, and -0.0028 QALYs in the PD-L1 TC ≥ 1% stage II - IIIA group, all stage II - IIIA groups, and the ITT group, and the ICERs were 108,825.37/QALY, 1,028,538.22/QALY, and -14,381,171.55/QALY, respectively. The ICERs all exceeded the WTP threshold of $27,354 per QALY (three times the per capita gross domestic product of China in 2022), and univariate sensitivity analysis showed that the price of atezolizumab played a crucial role in the model results. PSA showed that the probability of cost-effectiveness of atezolizumab in the PD-L1 TC ≥ 1% stage II - IIIA group, all stage II - IIIA groups, and the ITT group increased with the increasing WTP threshold.ConclusionFrom the perspective of China's health care system, in the PD-L1 TC ≥ 1% stage II - IIIA group, all stage II - IIIA groups, and the ITT group, the use of atezolizumab in the adjuvant treatment of patients with early-stage NSCLC after platinum-based chemotherapy is unlikely to be cost-effective. The implementation of PAP or price reduction negotiations for atezolizumab might be among the most effective measures to improve its cost-effectiveness.

Project description:PurposeThe phase III ADAURA (ClinicalTrials.gov identifier: NCT02511106) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non-small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30]; P < .001). We report an updated exploratory analysis of final DFS data.MethodsOverall, 682 patients with stage IB-IIIA (American Joint Committee on Cancer/Union for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years. The primary end point was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test; following early reporting of statistical significance in DFS, no further formal statistical testing was planned. Secondary end points included DFS in stage IB-IIIA, overall survival, and safety. Patterns of recurrence and CNS DFS were prespecified exploratory end points.ResultsAt data cutoff (April 11, 2022), in stage II-IIIA disease, median follow-up was 44.2 months (osimertinib) and 19.6 months (placebo); the DFS HR was 0.23 (95% CI, 0.18 to 0.30); 4-year DFS rate was 70% (osimertinib) and 29% (placebo). In the overall population, DFS HR was 0.27 (95% CI, 0.21 to 0.34); 4-year DFS rate was 73% (osimertinib) and 38% (placebo). Fewer patients treated with osimertinib had local/regional and distant recurrence versus placebo. CNS DFS HR in stage II-IIIA was 0.24 (95% CI, 0.14 to 0.42). The long-term safety profile of osimertinib was consistent with the primary analysis.ConclusionThese updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

Dataset Information

Stage as the Sole "Biomarker" for Adjuvant Pembrolizumab in Resected Stage IB to IIIA NSCLC without Considerations for PD-L1 Expression Level, ALK/EGFR Mutational Status, and Prior Adjuvant Chemotherapy per FDA Approval Indications of PEARLS/Keynote-091?

Publications

Stage as the Sole "Biomarker" for Adjuvant Pembrolizumab in Resected Stage IB to IIIA NSCLC without Considerations for PD-L1 Expression Level, ALK/EGFR Mutational Status, and Prior Adjuvant Chemotherapy per FDA Approval Indications of PEARLS/Keynote-091?

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