Home > Oncology > ASCO GU 2022 > Urothelial Carcinoma > Neoadjuvant enfortumab vedotin promising in MIBC ineligible for cisplatin

Neoadjuvant enfortumab vedotin promising in MIBC ineligible for cisplatin

Presented by
Prof. Daniel Petrylak, Yale School of Medicine, CT, USA
ASCO GU 2022
Phase 1/2, EV-103
Results from the phase 1b/2 EV-103 trial showed promising anti-tumour activity of neoadjuvant enfortumab vedotin in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin therapy.

Up to 1 in 4 patients diagnosed with urothelial cancer present with muscle-invasive disease, which has a substantial risk of progression or metastasis. Neoadjuvant chemotherapy has been shown to prolong overall survival for patients who are cisplatin-eligible [1]. The standard of care for cisplatin-ineligible patients undergoing surgery does not include neoadjuvant therapy. Enfortumab vedotin is an antibody-drug conjugate directed to Nectin-4, which is highly expressed in urothelial cancer and has been shown to benefit locally advanced or metastatic urothelial pre-treated cancer patients, including cisplatin-ineligible patients [2].

Cohort H of the EV-103 phase 1b/2 trial (NCT03288545) evaluated the anti-tumour activity of neoadjuvant enfortumab vedotin in patients with MIBC who are cisplatin-ineligible. Participants received 3 cycles of neoadjuvant enfortumab vedotin prior to radical cystectomy plus pelvis lymph node dissection. A total of 22 patients were treated, of which 19 patients completed all 3 cycles of enfortumab vedotin, 21 patients underwent a radical cystectomy, and 1 had a partial cystectomy. The primary endpoint was pathological complete response rate. Prof. Daniel Petrylak (Yale School of Medicine, CT, USA) presented the results [3].

Pathological complete response was observed in 36.4% (n=8) of patients; the pathological downstaging rate was 50% (n=11). The most common treatment-related adverse events were fatigue, alopecia, and dysgeusia. No surgeries were delayed due to enfortumab vedotin administration.

“The observed pathological complete response after neoadjuvant enfortumab vedotin showed promising activity in cisplatin-ineligible patients with MIBC. This justifies the ongoing phase 2 and phase 3 programmes which are evaluating enfortumab vedotin either alone or in combination with pembrolizumab in patients with MIBC,” concluded Prof. Petrylak.

  1. Pfister C, et al. Eur Urol. 2021;79:214–221.
  2. Powles T, et al. N Engl J Med 2021;384:1125–1135.
  3. Petrylak, DP, et al. Study EV-103 Cohort H: Antitumor activity of neoadjuvant treatment with enfortumab vedotin monotherapy in patients (pts) with muscle invasive bladder cancer (MIBC) who are cisplatin-ineligible. Abstract 435, ASCO GU 2022, 17–19 February.


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