Neoadjuvant immunotherapy delivers in cisplatin-ineligible bladder cancer

The use of pembrolizumab in the neoadjuvant setting appears to be associated with a higher rate of downstaging and a survival advantage among patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based neoadjuvant chemotherapy, according to a study presented at this year’s ASCO Genitourinary Cancers Symposium.

Among cisplatin-ineligible patients, those who received neoadjuvant pembrolizumab had a significantly higher pathologic complete response rate (pT0: 33 percent vs 13 percent; p=0.03) and longer overall survival (OS; median: not reached vs 19 months; p<0.01) than those who underwent immediate radical cystectomy. [ASCO GU 2023, abstract 513]

Propensity-score matched analysis further showed that the neoadjuvant pembrolizumab group had better survival after radical cystectomy, specifically at 12 months (89 percent vs 57 percent), 24 months (64 percent vs 28 percent), and 36 months (33 percent vs 13 percent; p<0.01 for all). The resulting median OS was not reached in the neoadjuvant pembrolizumab group as opposed to 21.0 months in the immediate radical cystectomy group (p<0.01).

Meanwhile, undergoing immediate radical cystectomy was associated with a twofold higher likelihood of worse survival as compared with receiving a neoadjuvant pembrolizumab regimen among cisplatin-ineligible patients with MIBC (hazard ratio, 2.0, 95 percent confidence interval, 1.1–3.89), reported lead author Dr Kyle Rose, a urologic oncology fellow at Moffitt Cancer Center in Tampa, Florida, US.

The findings are promising, given the unmet clinical need for systemic treatment options in patients with MIBC who are ineligible for cisplatin-based neoadjuvant chemotherapy, Rose noted.

In the PURE-01 trial, use of pembrolizumab in the neoadjuvant setting for the present population has been shown to be efficacious. The trial’s 3-year data provided evidence of the sustained efficacy of neoadjuvant pembrolizumab before radical cystectomy, with PD-L1 expression being the strongest predictor of sustained response after the procedure. [Clin Cancer Res 2022;28:5107-5114]

Nevertheless, Rose pointed out that while neoadjuvant pembrolizumab appears to be an attractive systemic option for cisplatin-ineligible patients with MIBC who are scheduled to undergo radical cystectomy, data from ongoing prospective randomized trials will help validate the present findings and establish the role of the immunotherapy regimen in the said population.

For the present analysis, Rose and colleagues used data from the PURE-01 trial and included 39 cisplatin-ineligible MIBC patients who received neoadjuvant pembrolizumab. Response and survival outcomes were compared against those of 313 patient counterparts who underwent immediate radical cystectomy at Moffitt Cancer Center. The median age of the propensity-score matched cohort (39 patients in each group) was 75 years, and 95 percent were men. Precystectomy ECOG status and clinical T stage were similar.