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The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer.

ABSTRACT: Lung cancer is the most common cancer and leading cause of cancer death. While targeted therapies have redefined treatment options for non-small cell lung carcinoma (NSCLC) with genetic aberrations such as epidermal growth factor and anaplastic lymphoma kinase, many patients do not harbour these oncogenic drivers. Cancer immunology has enabled the development of immune modulators that has dramatically altered the therapeutic landscape of advanced NSCLC. The success of immune-checkpoint inhibitors in pretreated NSCLC has led to the conduct of multiple studies exploring their role in the first-line setting. This article provides an overview of the evolving landscape of immune-checkpoint inhibitors with a focus on the programmed cell-death 1 (PD-1; pembrolizumab, nivolumab) and programmed cell-death ligand 1 (PD-L1; atezolizumab, durvalumab, avelumab) immune-checkpoint inhibitors as single agent or in combination with either chemotherapy or with another immune-checkpoint inhibitor in the treatment of NSCLC, the challenges faced, as well as future perspectives.

SUBMITTER: Low JL

PROVIDER: S-EPMC6716180 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer.

Low Jia Li JL Walsh Robert J RJ Ang Yvonne Y Chan Gloria G Soo Ross A RA

Therapeutic advances in medical oncology 20190828

Lung cancer is the most common cancer and leading cause of cancer death. While targeted therapies have redefined treatment options for non-small cell lung carcinoma (NSCLC) with genetic aberrations such as epidermal growth factor and anaplastic lymphoma kinase, many patients do not harbour these oncogenic drivers. Cancer immunology has enabled the development of immune modulators that has dramatically altered the therapeutic landscape of advanced NSCLC. The success of immune-checkpoint inhibitor ...[more]

PMID: 31497071

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Project description:IntroductionThe introduction of immuno-oncology (IO) therapies has changed the treatment landscape of non-small cell lung cancer (NSCLC). Numerous cost-effectiveness analyses (CEAs) and technology appraisals (TAs) evaluating IO therapies have been recently published.ObjectiveWe reviewed economic models of first-line (1L) IO therapies for previously untreated advanced or metastatic NSCLC to identify methodological challenges associated with modeling cost effectiveness from published literature and TAs and to make recommendations for future CEAs in this disease area.MethodsA systematic literature review was conducted following Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched MEDLINE, Embase, EconLit (January 2009-January 2020), and select conferences (since 2016) for CEAs of 1L IO treatments in patients with recurrent or metastatic, epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutation-negative NSCLC, published in English. TAs from England, Scotland, Canada, Australia, Germany, and France were also examined. Two reviewers screened the results and extracted the data. The quality of the CEAs was described using the Drummond checklist.ResultsIn total, 46 records reporting on 38 unique models met protocol-defined criteria and were included. Five models adjusted for treatment switching or crossover in base-case analyses, and the remainder considered treatment switching or crossover to represent clinical practice and made no adjustment. Seven models used external real-world data for survival modeling or extrapolation validation. Six models that assumed long-term treatment benefit stopped at 3 or 5 years after initiation. Seven models used the observed time-on-treatment distribution from the trial, and eight used progression-free survival for treatment duration. All models compared one or more IO monotherapies or combination therapies with chemotherapy. Only one study directly compared different IO agents but did not consider the concordance issue across programmed death-ligand 1 (PD-L1) testing methods. Utilities were modeled by health state in 12 models, four applied a time-to-death approach, and ten explored both. None applied cure models.ConclusionVariations in methodological challenges were seen across studies. Previous models took approaches that were followed in subsequent models, such as a 2-year stopping rule of IO duration or treatment-effect waning. Challenges such as heterogeneity in PD-L1 testing and survival extrapolation and validation using real-world data should be further considered for future models in advanced or metastatic NSCLC.

Project description:Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated. Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system. Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies. Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively. Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.

Dataset Information

The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer.

Publications

The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer.

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