Comparative benchmarking of regulatory drug approvals by Food & Drug Administration (FDA): A cross disease comparison with gynecologic malignancies.

e16584 Background: Gynecologic malignancies (GM) represent a major cause of cancer deaths. Improving outcomes of systemic therapy in GM requires development of new active anticancer drugs (AD), their regulatory approval and clinical adoption. Understanding regulatory approvals by the FDA may allow assessment of development in GM, cross disease comparisons and benchmarking. Methods: Using the FDA public website and drug labels we performed a cross sectional analysis of approved AD, indications for ST and GM (new molecular entity [NME], supplemental indications and orphan drugs designations [ODD]) and their supportive trials. Reformulations of previously approved AD, generics, adjunctive, preventive, local therapy, symptom management and noncancerous indications were excluded. Results: From 1990 to 2014, FDA approved 63 NMEs for 135 indications and 9 indications based on previously approved AD. ODD accounted for 28% of indications. GM approvals included 4 NMEs (Olaparib, Topotecan, Paclitaxel and Altretamine) and 11 indications (4 ODD). There were no approvals for endometrial and vulvo-vaginal cancers. No difference was found in NME approvals trend comparing ST to GM (p = 0.14); however, differences in the trial accrual process were detected (Table 1). Unique pivotal, randomized, phase 3 trials supported 61% vs 45% of indications for ST vs GM (p = 0.36), while non-randomized trials supported 10% vs 27% (p = 0.11). Overall survival led to approval of 40% and 36% indications in ST and GM. FDA granted 4 priority reviews and 2 accelerated approvals in GM compared to 66 and 29 in ST. Olaparib is the only biomarker guided approved AD for GM. Conclusions: Comparative benchmarking of pivotal trials and associated drug approval by FDA provide an evidence informed assessment of consistency and equity in regulatory approvals. GM make up 12% of all cancers in US, however GM indications represent 8 % of all ST approvals over the last 25 years. ST GM P value Size: randomized patients, median 577 358 0.011 Sites, median 98 43 0.016 Countries, median 16 7 0.004 Accrual time, days 734 943 0.76 Time to approval, days 183 181 0.98