Rikiya Taoka, Keita Tamura, Takuya Tsujino, Keita Kobayashi, Makito Miyake, Kohei Ogawa, Yutaro Sasaki, Shuichi Tatarano, Satoshi Katayama, Minoru Kato, Hideo Fukuhara, Yohei Abe, Yuki Oda, Ryoei Minato, Ryu Shigehisa, Teruo Inamoto, Haruhito Azuma, Koji Shiraishi, Kiyohide Fujimoto, Koichiro Wada, Junya Furukawa, Hideki Enokida, Motoo Araki, Junji Uchida, Keiji Inoue, Mikio Sugimoto, West Japan Uro-oncology Collaboration Group
An institutional dexamethasone-premedication strategy was associated with reduced cutaneous toxicity during first-line enfortumab vedotin plus pembrolizumab. Exploratory analyses found no significant differences in response or PFS; adequately powered studies with longer follow-up should determine whether dexamethasone premedication affects antitumor efficacy.
BACKGROUND: Cutaneous toxicity is common during enfortumab vedotin plus pembrolizumab, but evidence for prophylaxis is limited. We evaluated whether institutional prophylactic intravenous dexamethasone before enfortumab vedotin was associated with reduced cutaneous toxicity in locally advanced or metastatic urothelial carcinoma.
METHODS: This multicenter prospective cohort enrolled 172 patients at 11 Japanese institutions. Before enrollment, three institutions adopted fixed dexamethasone (6.6 mg) premedication and eight did not; policies remained unchanged, and patients were not individually allocated. The primary endpoint was any-grade skin reaction. Best radiographic response was a prospectively specified exploratory analysis, and progression-free survival (PFS) was evaluated post hoc.
RESULTS: Forty-one patients were treated under the dexamethasone-premedication policy and 131 under the no-premedication policy. Any-grade skin reactions occurred in 36.6% and 64.9% of patients, respectively (P = 0.003), and grade ≥ 2 reactions occurred in 14.6% and 35.1% (P = 0.022). Dexamethasone was independently associated with lower risks of any-grade (adjusted odds ratio, 0.35; 95% confidence interval, 0.16-0.76) and grade ≥ 2 reactions (adjusted odds ratio, 0.27; 95% confidence interval, 0.10-0.73). Cumulative enfortumab vedotin exposure through two cycles was similar. In exploratory analyses, objective response rates were 61.1% and 63.1%; median PFS was not reached, and 6-month PFS rates were 67.3% and 73.9%, respectively (hazard ratio, 1.28; 95% confidence interval, 0.68-2.39; log-rank P = 0.440).
CONCLUSIONS: An institutional dexamethasone-premedication strategy was associated with reduced cutaneous toxicity during first-line enfortumab vedotin plus pembrolizumab. Exploratory analyses found no significant differences in response or PFS; adequately powered studies with longer follow-up should determine whether dexamethasone premedication affects antitumor efficacy.