This analyzes the innovativeness, clinical evidence, and efficacy of new drug indications with US Food and Drug Administration (FDA) approval for breast, ovarian, endometrial, and cervical cancer.
We identified 26 drugs with FDA approval in 55 gynecological cancer indications from 2000 to 2021. For each indication, we collected drug, indication, and clinical trial characteristics from FDA labels. Hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), and relative risk (RR) for tumor response were meta-analyzed. Monthly treatment costs were calculated for US patients covered under Medicare & Medicaid.
Of 55 indications, 36 received approval for breast, 12 for ovarian, 3 for endometrial, and 4 for ovarian cancer. Drugs acted via a targeted (84%), immune-regulating (13%), and cytotoxic (4%) mechanism of action. Approval was granted to 34 (62%) small-molecules, 16 (29%) antibodies, and 5 (9.1%) antibody-drug conjugates. Indications were predominantly first-or second-line (82%) combination therapies (62%) with a biomarker (84%). Indications frequently received the orphan (24%), fast track (20%), accelerated approval (27%), priority review (82%), and breakthrough therapy (40%) designation. Approval was mostly supported by double-blind (51%) phase 3 (75%) randomized-controlled (82%) trials enrolling a median of 521 patients (IQR: 302-724) for 3.8 years (IQR: 2.5-5.2). On average, new drugs HRs were 0.79 for OS (95%CI: 0.75-0.82) and 0.55 for PFS (95%CI: 0.50-0.60), whereas tumor response was 1.48 (95%CI: 1.37-1.60). Novel drugs increased patient survival by a median of 3.20 months for OS (IQR, 2.0-4.90 months) and 4.75 months for PFS (IQR, 2.40-7.10 months). Greater OS benefits were observed for drugs with a biomarker (HR: 0.76 vs. 0.84, p=.034). In 2022, Gynecological cancer drugs cost an average of $13,053.30 per month.
Over the past 22 years, the approval of innovative and effective drugs transformed the landscape of gynecological cancer treatments. Especially biomarker-guided targeted therapies resulted in substantial improvements in OS and PFS. However, rising drug prices pose a challenge to healthcare systems and patient access.