<p>Economic Evaluation of Single versus Combination Immuno-Oncology Therapies: Application of a Novel Modelling Approach in Metastatic Melanoma</p>

Abstract

Background: Existing economic model frameworks may not adequately capture the atypical treatment response patterns in immuno-oncology (I-O) compared with conventional therapies and thus may fail to represent the full clinical value associated with disease dynamics and improved survival. Objective: A cost-effectiveness analysis (CEA) of the I-O Regimen (nivolumab/ipilimumab) versus ipilimumab alone in advanced melanoma was carried out by applying a 5-state partitioned survival model (PSM) as a case study, to explore the I-O treatment response and clinical outcomes. The findings were compared with those of a conventional 3-state PSM. Materials and Methods: The case study extends the conventional 3-state PSM, by separating the pre-progression state into non-responders and responders, and the post-progression state into normal and I-O progression to account for delayed treatment effects preceding clinical response. Model states were populated using patient-level data (where possible), mapping from the best overall response (BOR), and survival analysis with flexible and traditional parametric methods. Survival functions were applied to progression-free survival (PFS) and overall survival (OS) endpoints across treatment arms using the 4-year follow-up data (data available at the time of the research; since then 5-year follow-up data have been published) from the CheckMate 067 trial. Information on BOR was used as a means of differentiating the I-O treatment response in addition to the outcomes of progression-free and progressed disease. A UK National Health Service and personal social services (NHS/PSS) perspective over a lifetime horizon was used with outcomes discounted at 3.5% annually. Results: The 5-state PSM generated an increase in quality adjusted life years (QALYs) in both treatment arms and gave a more granular description of patients' health profiles compared with the traditional 3-state PSM. The incremental QALY increased by 13% (from 2.62 to 2.95 QALYs) and the incremental cost decreased by 12% (£29,125 to £25,678) with the 5-state model. In both models, the Regimen had an incremental cost-effectiveness ratio (ICER) relative to ipilimumab alone within the lower bound of the National Institute for Health and Care Excellence (NICE) reference range (£20,000 per QALY gained). Conclusion: A 5-state economic model, incorporating relevant I-O health states, can be more informative to gain insight into treatment response and progression differences that are not commonly captured in existing economic models. Clinical trial endpoints, including those relating to treatment response, which are not directly reported in ongoing I-O trials, can be mapped on to the proposed modelled health states (although assumptions are required to do so). Improvements in reporting treatment response in future I-O clinical trials could help to further validate and improve the proposed model framework.

Economic evaluation of nivolumab combined with ipilimumab in the first-line treatment of advanced melanoma in Japan

“…These results from the Japanese perspective are consistent with prior economic evaluations for nivo þ ipi conducted from other country perspectives. Gibson and colleagues conducted a similar three-state partitioned survival analysis also based on the 48-month CheckMate 067 data, as well as a five-state analysis, from the UK perspective comparing nivo þ ipi to ipilimumab, over a 40-year time horizon 31 . In this analysis, they estimated the incremental cost per QALY gained vs. ipilimumab to be approximately $11,000-$15,000 (adjusted to 2019 US$ from GBP) across the models, which is aligned with the roughly $15,000 per QALY estimated in the analysis for Japan.…”

Modeling Challenges in Cost-Effectiveness Analysis of First-Line Immuno-Oncology Therapies in Non-small Cell Lung Cancer: A Systematic Literature Review

“…Response-based modeling has been employed in other indications but not yet in NSCLC. Gibson et al [ 56 ] compared economic evaluations of nivolumab in combination with ipilimumab in patients with metastatic melanoma using a conventional three-state PS approach and a five-state PS approach, splitting pre-progression state by response status and post-progression state by 1L treatment type (IO vs. conventional therapies). The OS and PFS estimates from both approaches were identical, whereas the five-state approach provided more granularity in terms of response breakdown; consequently, response-specific utility data can be applied to differentiate between utility level of pre-progression patients with or without response.…”

“…Lack of RWD on long-term benefits of IOs makes it challenging to develop robust assumptions for model development. Related to this challenge is how to model delayed clinical benefit and how to address truncated survival curves for patients receiving IO [ 56 ].…”