Background: Many FDA-approved cancer therapies, whether as a multiagent combination or as a single agent, have demonstrated only modest clinical benefit. To investigate the drug development landscape, this analysis focuses on whether newly approved drugs are added to existing standards as combination therapy or replace a former drug as monotherapy.
Methods: A retrospective analysis of package inserts and corresponding trials for the treatment of nonhematology solid tumor malignancies from January 2011 to December 2023 was conducted to categorize an approval as monotherapy or combination therapy. Drug characteristics, treatment indications, study design, approval history, and efficacy results were compared between the 2 cohorts.
Results: Among the 292 approval entries and 110 drugs, 193 (66.1%) were monotherapies and 99 (33.9%) were combinations. Combinations, when compared with monotherapies, were more frequently approved as regular than accelerated approval (85 [85.9%] vs 132 [68.4%], P <.01), in the first-line setting (66 [66.7%] vs 69 [35.8%], P <.01), and with overall survival as the criteria (49 [49.5%] vs 40 [20.7%], P <.01). Monotherapies were more likely to be novel drugs compared with combinations (80 [41.5%] vs 14 [14.1%] P <.01). Monotherapies were more likely to be small molecule targeted agents, while combinations were more likely to be immunotherapies (P <.02). There was no difference comparing the time-to-event endpoints and validated clinical benefit scale, but the median response rate of combinations (46%) was higher than monotherapies (34%, P <.01).
Discussion: Given that clinical benefit appears limited in combination therapy compared with monotherapy, drug development could focus on simplifying cancer therapies toward patient-centered paradigms.
Keywords: FDA approval; cancer drugs; combination agents; monotherapy; solid tumors.
© The Author(s) 2024. Published by Oxford University Press.