Characteristics and outcomes of new molecular oncology drug approvals, in combination or monotherapy

Importance: Understanding the factors that are associated with new molecular entity (NME) cancer drug approvals as a single agent and in combination, and European Society for Medical Oncology (ESMO) scores, can aid in identifying suitable factors to consider in trial designs for future drugs. In addition, the association between the various outcomes can aid in determining benefit when surrogate outcomes are used in approval consideration.Objective: This study aims to (1) use the measures used in evaluating clinical trials by ESMO scores to determine the differences in the characteristics of 2013-2022 Food and Drug Administration (FDA) oncology NME drug approvals for those approved for use in combination or as a monotherapy, and (2) analyze the association between survival outcomes and the response rate for monotherapy NME drugs and/or drugs approved in combination.Design: Cross-sectional analysis.Setting: US FDA Oncology Drug Approvals (2013-2022)Participants: US FDA Oncology Drug Approvals (2013-2022)Exposures: Trial-level characteristics (tumor types, basis of approval, randomized or not, phase) and associations between overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) and whether NME drugs were approved as monotherapy or in combination .Results: Drugs approved for use as a monotherapy are less likely to be approved using a randomized study (p < 0.001) and more likely to be approved via the accelerated pathway (p = 0.012) and be open-label (p < 0.001). Drugs approved for use as a combination or monotherapy significantly differed on their approval basis (p = 0.002), phase of trial at the time of approval (p = 0.02), and ESMO scores (p = 0.02). There was low correlation between response rate and either PFS or OS metrics. However, nearly all of the drugs with large improvements in OS (> 5months) were drugs with robust ORR.Conclusions and relevance: Drugs approved as monotherapy with a low response rate are likely to have marginal benefit in OS and PFS.