Evaluating the value of checkpoint inhibitor therapy using the ASCO and ESMO frameworks.

Abstract

17 Background: The advent of checkpoint inhibitor therapy (CIT) has dramatically changed the oncology landscape, but is associated with significant costs. A positive randomized clinical trial (RCT) may not translate to meaningful outcomes for patients. The American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) have developed frameworks to quantify the value of cancer treatment. We applied these frameworks to RCTs involving CIT in order to explore the relationship between trial outcomes and magnitude of clinical benefit. Methods: A literature search was conducted to identify CIT RCTs. Data extracted included study characteristics, pre-specified estimated hazard ratios (eHR) and observed HR (oHR). ASCO Value Framework version 2016 and ESMO Magnitude of Clinical Benefit (MCB) scale v1.1 were applied to each publication by 2 authors independently. Results: 30 RCTs (3 adjuvant, and 27 advanced setting) using CIT were identified between January 2010- October 2018. The majority of trials were in lung cancer (37%) and melanoma (36%). The eHR was 0.71±0.06 (range: 0.55-0.78), and oHR was 0.76±0.15 (range: 0.49 – 1.11). 54% RCTs did not achieve eHR, with a difference of 0.16±0.12 (range: 0.01 – 0.41). ASCO framework scores ranged -24.0 to 71.3, far below the maximum potential score of 180. 18 RCTs formed the basis for FDA approvals. The mean ASCO framework score was 45.6 ± 16.6 (range: 14.4 - 71.3) for FDA approved indications, and 14.0 ± 18.4 (range: -24 – 49) for non-FDA approvals (p < 0.001). All FDA approvals scored grade 4 or 5 on the ESMO MCB scale, indicating a meaningful clinical benefit. Many non-FDA approved RCTs did not receive an MCB grade as they were negative trials. There was no difference in the ASCO framework scores between MCB grade 4 and 5 RCTs. 3 adjuvant RCTs had an ASCO framework score ranging from 20.5 to 38.7 despite an MCB Grade A. Conclusions: Many trials did not meet the pre-specified eHR. FDA approval had statistically significantly higher NHB scores than non-FDA approvals, and they were deemed to have a meaningful clinical benefit according to the ESMO MCB scale. ASCO framework scores may require re-calibration since the highest score achieved in CIT RCTs was only 40% of the maximum score.