Highlighting Impactful ASCO GU Research Across Disease States

The 2026 ASCO Genitourinary Cancers Symposium (ASCO GU) featured key advances, particularly in the muscle-invasive bladder cancer (MIBC) and advanced renal cell carcinoma (RCC) space. In a discussion with CancerNetwork®, Alexander Z. Wei, MD, discussed a few of the most impactful abstracts presented at the conference.

Firstly, the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124), which evaluated enfortumab vedotin-ejfv (EV; Padcev) delivered perioperatively plus pembrolizumab (Keytruda) vs platinum-based chemotherapy in MIBC, displayed improvements in event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) with the investigational regimen.¹ Specifically, the EV/pembrolizumab regimen conferred a median EFS of not reached vs 48.5 months with chemotherapy alone, 24-month OS rates of 86.9% vs 81.3% (HR, 0.65; 95% CI, 0.48-0.89; P = .0029), and pCR rates of 55.8% vs 32.5%. Wei expressed that many of his colleagues went back to the clinic adopting the regimen based on the results.

Then, he highlighted findings from the first interim analysis of the phase 3 LITESPARK-022 study (NCT05239728), which evaluated pembrolizumab with or without belzutifan (Welireg) in clear cell RCC (ccRCC).² Although the median investigator-assessed disease-free survival (DFS) was not reached in the combination or pembrolizumab monotherapy arms, the 12-, 24-, and 30-month rates were 91.9% vs 85.2%, 80.7% vs 73.7%, and 75.8% vs 68.6%, respectively. He explained that the findings from this trial “move the needle forward” in the adjuvant setting.

Finally, he highlighted findings from the second interim analysis of the phase 3 LITESPARK-011 trial (NCT04586231), which assessed belzutifan and lenvatinib (Lenvima) vs cabozantinib (Cabometyx) in advanced RCC. The experimental combination conferred an improved objective response rate (ORR) and progression-free survival (PFS).³ Specifically, the median PFS was 14.8 months vs 10.7 months in each respective arm (HR, 0.70; 95% CI, 0.59-0.84; P = .00007), and the ORR was 52.6% (95% CI, 47.3%-57.7%) vs 40.2% (95% CI, 35.2%-45.3%).

Wei is an assistant professor of medicine (Hematology/Oncology) at the Columbia University Medical Center.

Transcript:

It was an exciting conference. The biggest trial that was presented was the results from EV304. EV304 was a study looking at the combination of enfortumab vedotin plus pembrolizumab compared with platinum-based chemotherapy in the perioperative setting for muscle invasive bladder cancer. This is a space that hasn’t moved in a while, until last year, when enfortumab vedotin/pembrolizumab started coming into the cisplatin-ineligible space. Then we were all wondering this year, what was going to happen with the cisplatin-eligible population? The results were, unsurprisingly, very good.

Patients had a pCR rate after enfortumab vedotin/pembrolizumab of about 55%. If you include patients who refused cystectomy, it went up to 65%. As far as studies that can impact what we do in clinical practice [go], this changes things right after the weekend. A lot of people went back to clinic on Monday and started using neoadjuvant enfortumab vedotin and pembrolizumab for muscle invasive bladder cancer.

Other studies were presented in the kidney cancer space. The LITESPARK studies were also [quite] impressive. In the adjuvant setting, belzutifan plus pembrolizumab compared with pembrolizumab alone led to a survival benefit, and that moves the needle forward in the adjuvant space for kidney cancer.

Additionally, in the second-line space in advanced kidney cancer, belzutifan plus [lenvatinib] compared with cabozantinib was also a positive trial. [For] patients who were previously treated with checkpoint inhibitors, often the question was, what was second line treatment? This trial answered that profoundly, where the combination of the HIF-2⍺ inhibitor, belzutifan, plus lenvatinib was positive compared with cabozantinib.

References

1. Galsky MD, Valderrama BP, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: randomized, open-label, phase 3 KEYNOTE-B15 study. J Clin Oncol. 2026;44(suppl 7):LBA630. doi:10.1200/JCO.2026.44.7_suppl.LBA630
2. Choueiri TK, Motzer RJ, Karam JA, et al. Adjuvant pembrolizumab plus belzutifan versus pembrolizumab for clear cell renal cell carcinoma (ccRCC): the randomized phase 3 LITESPARK-022 study. J Clin Oncol. 2026;44(suppl 7):LBA418. doi:10.1200/JCO.2026.44.7_suppl.LBA418
3. Motzer RJ, Park SH, McDermott RS, et al. Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti-PD-(L)1 therapy: open-label phase 3 LITESPARK-011 study. J Clin Oncol. 2026;44(suppl 7):417. doi:10.1200/JCO.2026.44.7_suppl417