EV-201 enrolled patients into two cohorts. Cohort 1, which was presented by Dr. Petrylak, enrolled patients who progressed after both anti-PD-1/L1 immunotherapy and platinum-based chemotherapy. Patients in cohort 1 were required to have good performance status (ECOG ≤1) and have no ongoing grade ≥2 sensory neuropathy. A total of 125 patients were treated with EV (1.25 mg/kg on days 1,8, and 15 of a 28 day cycle). The primary endpoint was ORR by RECIST v1.1.
Baseline characteristics were notable for a preponderance of patients with visceral metastases (90%), including 40% of patients with liver metastases, a cohort which has been very challenging to treat. Furthermore, cohort 1 was very heavily pre-treated, with a median of three prior systemic therapies. Although not required for enrolment, nectin-4 expression was identified within the tumors of every single patient.
With respect to the primary outcome, investigators report a noteworthy objective response rate of 44% in this heavily pre-treated poor-prognostic population. Of 125 patients, 15 (12%) achieved a complete response, and an additional 40 (32%) achieved partial responses. Responses were generally identified at first assessment, with a median time to response of 1.8 months and a median duration of response of 7.6 months (range 1.0 – 11.3 months). Cohort 1 achieved a median progression-free survival of 5.8 months and a median overall survival of 11.7 months, which compares very favorably to historical data on platinum-refractory metastatic urothelial cancer.
EV was generally well-tolerated, with only 12% of patients discontinuing for toxicity, most commonly with sensory neuropathy (6%).
Dr. Petrylak notes that, if approved, EV will likely constitute the standard of care in platinum-refractory anti-PD-1/L1 refractory metastatic urothelial cancer; a randomized confirmatory phase III trial, EV-301 is actively enrolling. Furthermore, EV-103 will assess the feasibility of combining EV with anti-PD-1/L1 immunotherapy and/or chemotherapy.
Presented by: Daniel Peter Petrylak, MD, Medical Oncologist, Professor of Medicine and of Urology, Yale School of Medicine and Yale Cancer Center, New Haven, Connecticut, United States
Written by: Michael Lattanzi, MD, Internal Medicine Resident, Department of Medicine, NYU School of Medicine, Twitter: @MikeLattanzi at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA
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