According to a phase 1b/2 trial, neoadjuvant chemo-immunotherapy resulted in significant down-staging prior to definitive surgery for patients with muscle-invasive urothelial carcinoma, whether they were cisplatin-eligible or -ineligible.

Jason Brown, University Hospitals Seidman Cancer Center, Cleveland, OH, presented results on Friday, February 17, 2023, at the 2023 ASCO Genitourinary Cancers Symposium in San Francisco, CA.

This multi-institutional, 2-stage study enrolled 82 patients with urothelial carcinoma with clinical stage T2-4N0M0, to either the cisplatin-eligible (n = 42) or the cisplatin-ineligible (n = 40) cohort. All patients received 5 doses of 200 mg pembrolizumab every 3 weeks. Cisplatin-eligible patients received gemcitabine-cisplatin chemotherapy while cisplatin-ineligible patients received gemcitabine chemotherapy. Following the chemo-immunotherapy, patients went on to definitive surgery, either radical cystectomy or nephroureterectomy. The primary end point was pathologic muscle-invasive response rate as assessed by investigators as definitive surgery. Secondary end points included rate of definitive surgery, rate of pathological T0, relapse-free survival (RFS) at 18 months, and overall survival (OS) at 36 months.

Of the enrolled patients, 88.1% (37) of the cisplatin-eligible and 87.2% (34) of the cisplatin-ineligible went on to definitive surgery and were evaluable for the primary end point. The median follow-up duration was 54.8 months in the cisplatin-eligible cohort and 29.2 months in the cisplatin-ineligible cohort. For all evaluable patients, the pathologic muscle-invasive response rate was 54% in the cisplatin-eligible cohort and 41% in the cisplatin-ineligible. Of all patients, the 18-month RFS was 65.1% the 36-month OS was 65.7%.

The most common grade ≥3 toxicities, experienced in >20% of all patients, were anemia, hypertension, and neutropenia. Incidence of cytopenia was higher in the cisplatin-eligible cohort than the cisplatin-ineligible. Immune-related grade ≥3 adverse events included elevated liver enzymes, rash, pneumonitis, and colitis. There was 1 death, which occurred in the cisplatin-eligible cohort, due to post-operative sepsis.

Dr Brown and coauthors concluded, “Neoadjuvant chemo-immunotherapy demonstrated significant down-staging in [cisplatin-eligible and cisplatin-ineligible muscle-invasive urothelial carcinoma patients] prior to definitive surgery, meeting the primary endpoint.” They added, “Further phase III studies will be necessary to confirm the efficacy and safety of the regimens.”

Source:

Brown J, Kaimakliotis HZ, Kelly WK, et al. HCRN GU14-188: Phase Ib/II study of neoadjuvant pembrolizumab and chemotherapy for T2-4aN0M0 urothelial cancer. Presented at 2023 ASCO Genitourinary Cancers Symposium; February 17-19; San Francisco, CA. Abstract 448