FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma.
Elaine ChangChana WeinstockLijun ZhangRosane CharlabSarah E DorffYutao GongVicky HsuFang LiTiffany K RicksPengfei SongShenghui TangPeter E WaldronJingyu YuEias ZahalkaKirsten B GoldbergRichard PazdurMarc R TheoretAmna IbrahimJulia A BeaverPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2020)
On December 18, 2019, the FDA granted accelerated approval to enfortumab vedotin-ejfv (PADCEV; Astellas and Seattle Genetics) for treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a programmed cell death protein 1 or programmed death ligand 1 inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. Substantial evidence of effectiveness for this application is obtained from Cohort 1 of the single-arm, multicenter Study EV-201. Patients received enfortumab vedotin (EV) 1.25 mg/kg (up to a maximum dose of 125 mg) intravenously on days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable toxicity. Confirmed objective response rate in the 125-patient efficacy population determined by blinded independent central review was 44% [95% confidence interval (CI), 35.1-53.2], with complete responses in 12%. Median response duration was 7.6 months (95% CI, 6.3-not estimable). Grade 3-4 adverse reactions occurred in 73% of patients. Hyperglycemia, peripheral neuropathy, ocular disorders, skin reactions, infusion site extravasations, and embryo-fetal toxicity are labeled as warnings and precautions for EV. The article summarizes the data and the FDA thought process supporting accelerated approval of EV. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Keyphrases
- locally advanced
- squamous cell carcinoma
- end stage renal disease
- rectal cancer
- small cell lung cancer
- chronic kidney disease
- ejection fraction
- newly diagnosed
- neoadjuvant chemotherapy
- radiation therapy
- peritoneal dialysis
- randomized controlled trial
- oxidative stress
- study protocol
- systematic review
- low dose
- emergency department
- phase ii study
- computed tomography
- high grade
- deep learning
- artificial intelligence
- case report
- big data
- electronic health record
- smoking cessation
- protein protein
- squamous cell
- positron emission tomography
- combination therapy
- binding protein
- lymph node metastasis