Association of Immunotherapy With Durable Survival as Defined by Value Frameworks for Cancer Care

Abstract

Importance: Modern immuno-oncology agents have generated great excitement because of their potential to provide durable survival for some patients. However, there is concern regarding the cost of cancer care, and multiple frameworks have been developed to assess value. The American Society of Clinical Oncology (ASCO) framework awards bonus points if substantial durable survival is demonstrated.

Objective: To assess whether modern immuno-oncology agents reach defined efficacy thresholds in value frameworks.

Design, setting, and participants: In this analysis, all US Food and Drug Administration (FDA) approvals for immuno-oncology agents between March 2011 and August 2017 were reviewed. Data required for the ASCO framework were collected, specifically improvement in proportion of patients alive with the test regimen and survival rate with standard treatment.

Main outcomes and measures: Awarding of bonus points for durable survival based on the ASCO criteria.

Results: Twenty-three metastatic indications for 6 immuno-oncology agents (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, and durvalumab) were approved by the FDA from March 2011 to August 2017. Ten (43%) of the approvals were based on survival end points, while 13 (57%) were based on response rates. Only 3 drug indications fulfilled the threshold defined for the survival rate of patients receiving standard care (minimum 20%). Nine indications achieved the required level of improvement in proportion to patients alive in the test regimen compared with the standard (above 50%). There was overlap between these 2 criteria for 3 drug indications, allowing them to gain the durable survival bonus points awarded by the ASCO framework.

Conclusions and relevance: Durable survival and response rates of modern immuno-oncology agents are rarely recognized as significant by current oncology value frameworks. This may be due to insufficient demonstration of efficacy of such agents or inappropriately calibrated value frameworks.

Figure.. American Society of Clinical Oncology (ASCO) Framework Parameters for the Long Tail and Durable Survival Bonus Points

To be awarded ASCO bonus points, a drug must meet 2 thresholds: achieving a 50% or greater improvement (blue dotted line) in proportion of patients alive with the test regimen at twice the median overall survival or progression-free survival time point (9 drugs met this requirement) (A) and 20% of patients surviving (blue dotted line) with the standard regimen (3 drugs met this requirement) (B). Only 3 drugs reached both thresholds and met ASCO criteria for bonus points. Drugs using objective response rate as the primary end point are not eligible to gain the bonus points related to the survival tail and are therefore not presented here. HNSCC indicates head and neck squamous cell carcinoma; NSCLC, non–small cell lung cancer.