Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer
Is this the end of the cisplatin era in bladder cancer? It sure seems that way. The results here are no surprise based on the signal we saw in the metastatic setting.
Is this the end of the cisplatin era in bladder cancer? It sure seems that way. The results here are no surprise based on the signal we saw in the metastatic setting.
At 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin–pembrolizumab group and 39.4% in the control group (hazard ratio) HR 0.4 estimated overall survival was 79.7% and 63.1% HR 0.50. Perioperative enfortumab vedotin plus pembrolizumab new standard of care for cisplatin ineligible patients who are candidates for surgery.
Circulating tumor DNA (ctDNA) was used to identify patients who may benefit from adjuvant immunotherapy. Among ctDNA-positive patients, those who received adjuvant atezolizumab demonstrated improved progression-free survival (PFS) and overall survival (OS) compared with placebo (median OS, 32 vs 24 months). Patients with persistently negative ctDNA results had 1-year disease-free survival (DFS) of 95% and 2-year DFS of 88%.
Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder.
Perioperative durvalumab showed an improvement of 2-year OS of 82.2 vs 75.2%, 2-year PFS was improved 67.8 vs 59.8%. There was interestingly no difference in the rates of grade 3-4 toxicity in the SOC vs periop-IO group. This is likely going to become the SOC in resectable bladder cancer.
Many had neoadjuvant therapy, still no difference between standard or extended lymphadenectomy for muscle-invasive bladder cancer. So, it seems more is not better.
The poor OS of 1.5 years in node-positive patients is striking in this retrospective review of 287 patients treated with definitive intent. The OS was not different between those treated with TURBT + chemoradiation vs. chemotherapy + radical cystectomy, suggesting that surgery may not be superior to multi-modal therapy and QOL may be superior in a non-operative approach.
Retrospective review showing equivocal outcomes in cT2-T4N0 patients treated with radical cystectomy vs TURBT + chemoradiation. There were similar rates of neoadjuvant chemotherapy being given in both groups. Based on prospective data, the SOC remains cisplatin-based neoadjuvant chemo followed by radical cystectomy; however, trimodality therapy may not have worse outcomes, and it would be great to see a prospective head-to-head study.