317 Background: The U.S. Food and Drug Administration (FDA) oversees cancer drug approvals in the United States but has an international influence. The FDA is tasked with balancing timely access with the need for robust evidence demonstrating patient-relevant benefit. However, curative setting drugs are likely held to a different standard given curative intent, larger eligible population pool, lack of response assessment, and possibility of harms. Methods: We assessed FDA approvals of cancer drugs for curative-intent for adult solid cancers from the last 20 years (2006 to 2025). Results: We identified 44 unique approvals, including 43 regular and 1 accelerated approval, of which 60% were granted in the last 5 years. Breast cancer (n = 9), non–small-cell lung cancer, NSCLC (n = 8) and melanoma (n = 7) accounted for the largest share of approvals, with NSCLC accounting for 26% of approvals between 2021-2025. Immunotherapy (53%) and targeted therapy (24%) predominated overall. Targeted therapies were most common in 2006–2010 (50%) and 2016–2020 (40%), whereas immunotherapy dominated 2011–2015 (67%) and 2021–2025 (70%). Hormone therapy, kinase inhibitors, chemotherapy and antibody-drug-conjugates accounted for 20% of all approvals. Most approvals were in the adjuvant setting (61%), followed by perioperative (16%) and neoadjuvant (9%) setting. Median adjuvant treatment duration was 52 weeks, with longest median duration for melanoma (5 years), and shortest duration for head and neck cancer (18 weeks). Biomarker-driven indications accounted for 24% of approvals. Primary endpoints included disease-free survival (DFS/iDFS), event-free survival (EFS), metastasis-free survival, overall survival (OS), progression-free survival, relapse-free survival (RFS), and (pathologic) complete response. (i)DFS was the most commonly used endpoint (36%), followed by EFS (23%) and RFS (18%). Four trials had OS as a (co-)primary endpoint. Median improvement in 3-year (i)DFS was 9% (range 1.8–50) with drugs in breast cancer offering lowest magnitude of benefit (median 3-year iDFS gain of 5.4%), while drugs in NSCLC offered highest magnitude of benefit (median 3y DFS gain of 23.8%). Among trials with available ESMO-MCBS scores, 84% were graded A, 6% B, and 10% C. Between 2021-2025 all were graded A. Conclusions: Our analysis shows an increase in number of curative setting approvals in the last 5 years, specially immunotherapies and targeted drugs. However, the duration of treatment has also been increasing, and yet, the magnitude of benefit remains modest. 2006-2010 2011-2015 2016-2020 2021-2025 Number of approvals, n (%) 4 (9%) 3 (7%) 10 (23%) 27 (61%) Immunotherapy, n (% of time period) 1 (25%) 2 (67%) 2 (20%) 19 (70%) Targeted therapy, n (% of time period) 2 (50%) 1 (33%) 4 (40%) 4 (15%) Biomarker-driven approval, n (% of time period) 2 (50%) 1 (33%) 5 (50%) 3 (11%) Adjuvant treatment duration (weeks) 52 208 76.9 62.8 3-year (i)DFS gain NA NA 21.5 11.3
Teuwen et al. (Tue,) studied this question.