Comparison of Long-term Survival Benefits in Trials of Immune Checkpoint Inhibitor vs Non–Immune Checkpoint Inhibitor Anticancer Agents Using ASCO Value Framework and ESMO Magnitude of Clinical Benefit Scale

Abstract

IMPORTANCE Recently, anticancer agents have generated excitement owing to their capacity to preserve long-term durable survival in some patients who are represented by a tail of the survival curve. However, because traditional measures of clinical benefit may not accurately capture durable survival, amendments to various valuation frameworks have been proposed to capture this benefit. OBJECTIVES To determine how frequently immune checkpoint inhibitor (ICI) anticancer agents vs non-ICI anticancer agents displayed trends of long-term durable survival, as defined by the American Society of Clinical Oncology Value Framework version 2 (ASCO-VF v2) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1), as well as to further analyze the degree of agreement between ASCO and ESMO frameworks. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, anticancer agents from phase 2 or 3 randomized clinical trials (RCTs) cited for clinical efficacy evidence in drug approval by the US Food and Drug Administration between January 2011 and March 2018 were identified. Data required for the ASCO-VF v2 tail-of-the-curve bonus and the ESMO-MCBS v1.1 immunotherapy-triggered longterm plateau adjustments were extracted from relevant RCTs. Frequency and difference in proportions were calculated to determine how often survival benefits were awarded to anticancer agents overall and to ICI and non-ICI anticancer agents individually. MAIN OUTCOMES AND MEASURES American Society of Clinical Oncology Value Framework v2 tail-of-the-curve bonuses and ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments. RESULTS In total, 247 RCTs were identified, and 100 RCTs involving 57 164 patients were included, with 14 examining ICI agents (1 ipilimumab, 5 pembrolizumab, 5 nivolumab, 2 atezolizumab, and 1 durvalumab) and 86 examining non-ICI agents (74 targeted therapy, 8 chemotherapy, 3 hormone therapy, and 1 radiopharmaceutical). Randomized clinical trials were awarded ASCO-VF v2 tail-of-thecurve bonuses more often than ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments (ASCO-VF v2, 45.0% [8 of 14 ICI RCTs and 37 of 86 non-ICI RCTs] vs ESMO-MCBS v1.1, 2.6% [1 of 12 ICI RCTs and 1 of 66 non-ICI RCTs). Randomized clinical trials for ICIs were not more likely to receive an ASCO-VF v2 bonus or ESMO-MCBS v1.

Reassessing the Net Benefit of Cancer Drugs With Evolution of Evidence Using the ASCO Value Framework

“…In addition, the inherent interrater variability is a potential limitation within ASCO-VF scoring, as with any measurement tool. Nevertheless, after factoring previous literature into account, 6,15,16 we found that only a small number of cases differed, and our final findings remained the same after sensitivity analysis (results not shown). Finally, because only a small number of drugs approved under the accelerated approval pathway were included, the present study could not draw strong conclusions analyzing this subgroup.…”

Assessment of Food and Drug Administration– and European Medicines Agency–Approved Systemic Oncology Therapies and Clinically Meaningful Improvements in Quality of Life

“…19 The remaining scores were completed by 2 independent reviewers, with consultation of a third reviewer when necessary, with experience applying the valuation frameworks. 6 , 27 , 31 , 32 , 33 , 34 , 35 …”

Quantifying Value of Hope

“…Comparisons of ASCO's value framework with other scoring systems like the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale, which credits therapies demonstrating plateauing survival curves, revealed that very few (,3%) cancer treatments fulfilled the European Society of Medical Oncology criterion to receive points for long-term survival. 22,23 Furthermore, researchers outside of health economics have broadly defined the concept of hope to represent authentic spirit and comfort, 24 and they have accepted hope as an effective coping strategy that improves quality of life during end-of-life care. 25 In addition, we acknowledge that there may be other explanations for the choice patterns we have observed.…”