Fed Ghali, MD on key unanswered questions with perioperative EV/pembro

Data from the KEYNOTE-905/EV-303 trial (NCT03924895) demonstrated that enfortumab vedotin-ejfv (EV, Padcev) plus pembrolizumab (Keytruda), given before and after surgery, yielded significant improvements in event-free survival (0.40), overall survival (0.50), and pathological complete response rate (57% vs 9%) compared with surgery alone in patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC).¹

In a recent interview with Urology Times®, Fed Ghali, MD, outlines several key unanswered questions surrounding perioperative use of enfortumab vedotin plus pembrolizumab (EVP) in bladder cancer. Specifically, Ghali considers the potential to de-escalate therapy for patients who achieve a complete response to treatment.

Ghali is an assistant professor of urology at the Yale School of Medicine and a urologic oncologist at Yale Cancer Center in New Haven, Connecticut.

Ghali first considered the potential for some patients to avoid adjuvant portion of therapy, potentially guided by biomarkers. He contextualized this discussion in light of recent data showing that ctDNA can be used to guide adjuvant therapy with atezolizumab. The question, according to Ghali, is will this strategy work with the EV/pembro regimen.

Another area of active investigation is whether patients who achieve strong responses to EVP could safely avoid cystectomy. The speaker expresses caution, noting that current tools to determine a true clinical complete response are unreliable; prior studies have shown that even when pre-surgical assessments appear disease-free, residual tumor is often found at cystectomy. At this point in time, Ghali says he’s hesitant to move too fast in that direction for several reasons.

For starters, he notes, “I think that our ability to do to assess complete response without removing the bladder, what we call clinical complete response is quite poor.” He then cited a study out of MD Anderson showing that over half of the time, patients who were thought to have a complete response by resection ended up having a tumor still present when viewed under pathology.

REFERENCE

1. Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study. Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract LBA2. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA2.html.pdf