Abstract
IntroductionWhile no direct comparative data exist for crizotinib in ROS1+ non-small cell lung cancer (NSCLC), studies have suggested clinical benefit with this targeted agent. The objective of this study was to assess the cost-effectiveness of crizotinib compared to standard platinum-doublet chemotherapy for first-line treatment of ROS1+ advanced NSCLC.MethodsA Markov model was developed with a 10-year time horizon from the perspective of the Canadian publicly-funded health care system. Health states included progression-free survival (PFS), up to two further lines of therapy post-progression, palliation and death. Given a lack of comparative data and small study samples, crizotinib or chemotherapy studies with advanced ROS1+ NSCLC patients were identified and time-to-event data from digitized Kaplan-Meier curves were collected to pool PFS data. Costs of drugs, treatment administration, monitoring, adverse events and palliative care were included in 2018 Canadian dollars, with 1.5% discounting. An incremental cost-effectiveness ratio (ICER) was estimated probabilistically using 5000 simulations.ResultsIn the base-case probabilistic analysis, crizotinib produced additional 0.885 life-years and 0.772 quality-adjusted life-years (QALYs) at an incremental cost of $238,077, producing an ICER of $273,286/QALY gained. No simulations were found to be cost-effective at a willingness-to-pay threshold of $100,000/QALY gained. A scenario analysis assuming efficacy equivalent to the ALK+ NSCLC population showed a slightly more favorable cost-effectiveness profile for crizotinib.ConclusionsAvailable data appear to support superior activity of crizotinib compared to chemotherapy in ROS1+ advanced NSCLC. At the list price, crizotinib was not cost-effective at commonly accepted willingness-to-pay thresholds across a wide range of sensitivity analyses.
Highlights
While no direct comparative data exist for crizotinib in ROS1 proto-oncogene tyrosine-protein kinase (ROS1)+ non-small cell lung cancer (NSCLC), studies have suggested clinical benefit with this targeted agent
ROS1 proto-oncogene tyrosine-protein kinase (ROS1) rearrangements are found in approximately 1–2% of NSCLC cases and are generally considered mutually exclusive from other oncogenic mutations commonly found in NSCLC e.g., epidermal growth factor receptor (EGFR), KRAS, or anaplastic lymphoma kinase (ALK) mutations [3]
ROS1 and ALK receptor tyrosine kinases belong to the same insulin-receptor family, sharing close structural homology between the adenosine triphosphate (ATP)-binding kinase domains to which crizotinib binds with high affinity
Summary
While no direct comparative data exist for crizotinib in ROS1+ non-small cell lung cancer (NSCLC), studies have suggested clinical benefit with this targeted agent. The objective of this study was to assess the costeffectiveness of crizotinib compared to standard platinum-doublet chemotherapy for first-line treatment of ROS1+ advanced NSCLC. Crizotinib is a tyrosine kinase inhibitor with demonstrated effectiveness against echinoderm microtubuleassociated protein-like 4 (EML4)-ALK rearrangements as well as anti-tumour activity against biologically similar domains of ROS1 and another proto-oncogene receptor tyrosine kinase, MET [5, 6]. At the data cut-off date of May 14, 2014, the primary endpoint, objective response rate (ORR) derived by investigator assessment, was 72% (95% CI: 58–84%) among patients with ROS1+ advanced NSCLC (N = 50), and 85.7% (95% CI: 42.1–99.6%) among the seven patients who had not received prior treatment. In the updated analysis, published in 2019 with a median 62.6 months of follow-up, the median progression-free survival (PFS) was 19.3 months (95% CI: 15.2–39.1) and the median OS was 51.4 months (95% CI: 29.3-not reached) [8]
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