Real-world use of accelerated approval oncology drugs subsequently withdrawn in the United States.

e13573 Background: In 1992, the FDA launched the accelerated approval (AA) program using surrogate outcomes to expedite access to drugs for patients with serious conditions or unmet needs. From 1995–2024, 107 oncology indications demonstrated verified clinical benefit; 31 were withdrawn and 66 have ongoing trials. Some withdrawn indications continue to remain in the clinical practice guidelines. This study aimed to estimate the prevalence and timing of real-world use of withdrawn drugs within 5 oncology indications between 2015–2024 in the United States. Methods: Retrospective data were drawn from the ConcertAI Patient360 non-small cell lung (NSCLC), small cell lung (SCLC), breast, and bladder cancer electronic medical record datasets. Per indication, cohort A was defined as patients who received the AA drug for the respective indication between AA and indication withdrawal (IW) date, and cohort B were patients who met the FDA label indications between AA and IW date but did not receive the AA drug. Patients with multiple primary cancers were excluded. We calculated proportions of AA drug utilization between AA and IW, and the number of patients who received AA drugs post-IW. Results: Included AA drugs were mobocertinib (NSCLC), sacituzumab govitecan (bladder cancer), atezolizumab (breast cancer), nivolumab (SCLC), and pembrolizumab (SCLC). The median time from AA to IW was 31.0 (range 21.4-43.4) months. The proportion of eligible patients who received an AA drug ranged from 12.9% for pembrolizumab to 84% for atezolizumab. Mobocertinib cohort A patients (n = 18) compared to cohort B (n = 31) were younger (median age 60.5 vs 72 years) and had a larger proportion of women (72.2% vs 54.8%). Other noteworthy differences included better performance status and higher BMI. Additionally, one patient initiated mobocertinib after IW. The sacituzumab govitecan cohort A patients (n = 41) were younger (median age 66 vs 71 years) and a smaller proportion were women (14.6% vs 29.6%) compared to cohort B (n = 71). No notable differences in demographic or clinical characteristics were seen among the atezolizumab cohort A patients (n = 180) patients compared to cohort B (n = 34). 16 patients initiated atezolizumab treatment after IW. Similarly, no notable differences were seen among the cohort A patients with SCLC who received pembrolizumab (n = 27) or nivolumab (n = 155) compared to cohort B (n = 183 vs n = 165). 41 and 38 patients with SCLC initiated pembrolizumab and nivolumab, respectively, after IW. Conclusions: Findings indicate mixed real-world uptake of AA therapies and no consistent differences in patient characteristics. It appears care teams promptly follow regulatory guidance and cease initiating withdrawn AA drugs after IW. Pembrolizumab and nivolumab in SCLC indications that are retained in the clinical practice guidelines seem to be the exception to this trend. In light of this analysis, the AA process is functioning as designed.