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ESMO 2023

ESMO 2023: EV-103 Cohort L: Perioperative Treatment with Enfortumab Vedotin Monotherapy in Cisplatin-Ineligible Patients with Muscle Invasive Bladder Cancer

(UroToday.com) The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 was host to a non-prostate, genitourinary tumors mini oral session. Dr. Srikala Sridhar presented the results of EV-103 Cohort L, which evaluated the perioperative treatment with enfortumab vedotin (EV) monotherapy in cisplatin-ineligible patients with muscle invasive bladder cancer (MIBC).


Up to 25% of all patients diagnosed with urothelial cancers present with MIBC. The current guideline-recommended standard of care for patients with MIBC is neoadjuvant cisplatin-based chemotherapy followed by surgery, with adjuvant therapy recommended in high-risk patients.1 However, up to 50% of patients may be cisplatin-ineligible and are recommended to proceed with surgery alone. Due to the high rates of recurrence in cisplatin-ineligible patients treated with surgery alone, there remains a significant clinical unmet need for novel therapies in this setting. Previously, neoadjuvant EV in cisplatin-ineligible MIBC showed encouraging anti-tumor activity, with a pathologic complete response (pCR) proportion of 36% and pathologic downstaging of 50%.2 Importantly, there were no new safety signals, no delays to surgery, and a low incidence of grade 3 or worse EV-related treatment-emergent adverse events. EV-103 Cohort L (NCT03288545) examines a perioperative approach consisting of both neoadjuvant and adjuvant EV in cisplatin-ineligible patients with MIBC.

EV-103 Cohort L included patients with cisplatin-ineligible cT2-4aN0M0 or cT1-4aN1M0 urothelial carcinoma patients medically fit for a radical cystectomy + pelvic nodal dissection. Following enrollment, patients were given EV monotherapy (1.25 mg/kg) in 3-week cycles on days 1 and 8 for 3 cycles total. Following surgery, patients received the same regimen for 6 cycles. The primary endpoint was pCR, with secondary objectives of pathologic downstaging (pDS), event-free survival (EFS), disease-free survival (DFS), overall survival (OS), and safety and tolerability.
Cohort L included 51 patients. The median age was 74 years. 96% had ECOG performance status 0 – 1. The baseline stage was cT2N0 for 57% and cN+ for 10% of patients. 45% of patients had a creatinine clearance of 30 – 60 mL/min. 
82.4% of patients completed all 3 cycles of neoadjuvant EV, with all these patients completing surgery within a median time of 1.3 months from the last EV dose.

For pathologic outcomes, the pCR was 34% and pDS occurred in 42% of patients.
The majority of EV-related adverse events were grade 2 or lower. 57% of patients had skin reactions, with 1 patient dying of Stevens-Johnson syndrome. A third of patients had peripheral neuropathy. There were no delays to surgery secondary to EV-related treatment-emergent adverse events. The most common grade 3 or worse surgery-related adverse events were anemia, ileus, and urinary tract infection.
EV-103 Cohort L adverse events
Dr. Sridhar concluded as follows:

  • Enfortumab Vedotin continues to show promising antitumor activity in cisplatin-ineligible patients with muscle-invasive bladder cancer
    • Pathologic complete response of 34%; pathologic downstaging rate of 42%
  • The results are consistent with EV-103 Cohort H
    • The safety profile of Enfortumab Vedotin was similar to previously reported data from Enfortumab Vedotin in muscle-invasive bladder cancer and locally advanced/metastatic urothelial carcinoma
    • No new safety signals; but close monitoring for toxicities remains important
    • No surgeries were delayed due to Enfortumab Vedotin-related treatment-emergent adverse events
  • This first data disclosure from EV-103 Cohort L supports the ongoing phase 3 programs evaluating Enfortumab Vedotin in combination with pembrolizumab in MIBC (KN-905, KN-B15)
    • Additional follow-up will allow characterization of event-free survival, disease-free survival, and overall survival data from Cohort L

Presented by: Srikala Sridhar, MD, MSc, FRCPC, Professor, Department of Medicine, Princess Margaret Cancer Centre, Toronto, ON

Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023

References:
  1. Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114.
  2. Petrylak D, Flaig TW, Mar N, 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. J Clin Oncol. 2022;40:Supplement 6.