Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma
- 11 February 2021
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 384 (12), 1125-1135
- https://doi.org/10.1056/NEJMoa2035807
Abstract
Background Patients with advanced urothelial carcinoma have poor overall survival after platinum-containing chemotherapy and programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor treatment. Methods We conducted a global, open-label, phase 3 trial of enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and had had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor. Patients were randomly assigned in a 1:1 ratio to receive enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight on days 1, 8, and 15 of a 28-day cycle) or investigator-chosen chemotherapy (standard docetaxel, paclitaxel, or vinflunine), administered on day 1 of a 21-day cycle. The primary end point was overall survival. Results A total of 608 patients underwent randomization; 301 were assigned to receive enfortumab vedotin and 307 to receive chemotherapy. As of July 15, 2020, a total of 301 deaths had occurred (134 in the enfortumab vedotin group and 167 in the chemotherapy group). At the prespecified interim analysis, the median follow-up was 11.1 months. Overall survival was longer in the enfortumab vedotin group than in the chemotherapy group (median overall survival, 12.88 vs. 8.97 months; hazard ratio for death, 0.70; 95% confidence interval [CI], 0.56 to 0.89; P=0.001). Progression-free survival was also longer in the enfortumab vedotin group than in the chemotherapy group (median progression-free survival, 5.55 vs. 3.71 months; hazard ratio for progression or death, 0.62; 95% CI, 0.51 to 0.75; P<0.001). The incidence of treatment-related adverse events was similar in the two groups (93.9% in the enfortumab vedotin group and 91.8% in the chemotherapy group); the incidence of events of grade 3 or higher was also similar in the two groups (51.4% and 49.8%, respectively). Conclusions Enfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based treatment and a PD-1 or PD-L1 inhibitor.Keywords
This publication has 26 references indexed in Scilit:
- Enfortumab Vedotin Antibody–Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer ModelsCancer Research, 2016
- A novel PI3K/AKT signaling axis mediates Nectin-4-induced gallbladder cancer cell proliferation, metastasis and tumor growthCancer Letters, 2016
- Exploiting the Immunomodulatory Properties of Chemotherapeutic Drugs to Improve the Success of Cancer ImmunotherapyFrontiers in Immunology, 2015
- Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-upAnnals Of Oncology, 2014
- Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapyAnnals Of Oncology, 2013
- Advanced Urothelial Carcinoma: Overcoming Treatment Resistance through Novel Treatment ApproachesFrontiers in Pharmacology, 2013
- Phase III Trial of Vinflunine Plus Best Supportive Care Compared With Best Supportive Care Alone After a Platinum-Containing Regimen in Patients With Advanced Transitional Cell Carcinoma of the Urothelial TractJournal of Clinical Oncology, 2009
- Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urotheliumCancer, 2003
- Phase II Trial of Weekly Paclitaxel in Patients With Previously Treated Advanced Urothelial CancerJournal of Clinical Oncology, 2002
- Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma.Journal of Clinical Oncology, 1997