Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2

Autor: Elisabeth I. Heath, Andrea Necchi, Takahiro Kojima, Mark N. Stein, Michiel S. van der Heijden, Janet Trowbridge, Daniel P. Petrylak, Joyce Steinberg, Se Hoon Park, Evan Y. Yu, Yohann Loriot, Bradley Alexander McGregor, Michael R. Harrison, Arjun Vasant Balar, Shang-Ying Liang, Jonathan E. Rosenberg, Jae-Lyun Lee
Rok vydání: 2021
Předmět:
Zdroj: Journal of Clinical Oncology. 39:4524-4524
ISSN: 1527-7755
0732-183X
Popis: 4524 Background: Cisplatin (cis)-ineligible, platinum-naive patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) who progress on/after anti-PD-1/L1 treatment (tx) have a poor prognosis and few tx options. Enfortumab vedotin (EV), a Nectin-4-directed antibody-drug conjugate, demonstrated overall survival (OS) benefit in pts with la/mUC who previously received anti-PD-1/L1 tx and platinum-containing chemotherapy (EV-301). EV-201 (NCT03219333) is a pivotal, single-arm, 2-cohort (C) study. C2 enrolled cis-ineligible pts with prior anti PD-1/L1 tx and no prior platinum for la/mUC. Results of the C2 primary analysis were previously presented. In this updated analysis, with 3 additional mo of follow-up (f/u), all responders were followed for ≥6 mo after onset of response. Methods: Pts received 1.25 mg/kg EV on Days 1, 8, and 15 of each 28-day cycle. The primary endpoint was confirmed objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), progression-free survival (PFS), OS, and safety. Results: 91 pts were enrolled and 89 treated in C2. Median (m) age was 75 y (range: 49-90). Pts were cis-ineligible at baseline, primarily due to CrCl < 60 mL/min (78%). Primary tumor site was upper tract in 43%, and 79% had visceral mets, including 24% with liver mets. As of 04 Dec 2020 (data cut-off), m f/u was 16.0 mo and m tx duration was 6.0 mo (range: 0.3-24.6). Confirmed ORR per BICR was 51% (95% confidence interval [CI] 39.8-61.3), including 22% complete response (CR) among treated pts. mDOR was 13.8 mo (95% CI 6.4-not reached). mPFS and mOS were 6.7 mo (95% CI 5.0-8.3) and 16.1 mo (95% CI 11.3-24.1), respectively. All-grade and grade (G) ≥3 tx-related adverse events (TRAEs) were reported in 97% and 55% of pts, respectively. Most common all-grade TRAEs were alopecia (51%), peripheral sensory neuropathy (49%), and fatigue (34%). For TRAEs ≥G3, each preferred term occurred in < 10% pts. TRAEs of interest included skin reactions (61% all grade, 17% ≥G3), peripheral neuropathy (56% all grade, 8% ≥G3), and hyperglycemia (10% all grade, 6% ≥G3). Four deaths were previously reported as tx related by investigators: 3 events ≤30 d of first EV dose (acute kidney injury, metabolic acidosis, multiple organ dysfunction syndrome) and 1 > 30 d of last EV dose (pneumonitis). Conclusions: Efficacy and safety in this updated analysis of EV-201 C2 are consistent with the primary analysis. The majority of platinum-naive, cis-ineligible la/mUC pts who progressed on/after anti-PD-1/L1 tx responded to EV, with 22% achieving CR and mDOR exceeding a year. PFS and OS continue to be encouraging in this elderly population, with no new safety signals. These data show the potential for EV as a non-platinum option for cis-ineligible pts following anti-PD-1/L1 tx. Clinical trial information: NCT03219333.
Databáze: OpenAIRE
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