3-Year Efficacy of Neoadjuvant Pembrolizumab Before Radical Cystectomy For Muscle-Invasive Bladder Cancer

Follow-up Data From PURE-01 Study

Andrea Necchi, MD, IRCCS San Raffaele Hospital, Milan, Italy, shares follow-up data and subtype analyses from the phase 2 PURE-01 trial, evaluating neoadjuvant pembrolizumab and radical cystectomy for patients with muscle-invasive urothelial bladder cancer.

Dr Necchi discusses the 3-year event-free survival of 74.4%, and a 3-year overall survival of 83.8% reported in this update, including compelling results seen in certain subgroups of patients, such as those with residual high-risk disease and those in claudin-low and basal/squamous subtypes.

Transcript:

I'm Andrea Necchi. I'm professor of medical oncology at Vita-Salute San Raffaele in Milan, Italy, and director of Genitourinary Medical Oncology in San Raffaele Hospital in Milan, Italy. It's a pleasure to be here today briefly presenting the updates from the PURE-01 study that have been published recently in a Clinical Cancer Research.

The PURE-01 study was a phase 2 study testing neoadjuvant pembrolizumab before radical cystectomy in patients with muscle invasive urothelial bladder cancer. Patients were selected according to clinical stage, and regardless of cisplatin-eligibility. They received 3 courses of neoadjuvant pembrolizumab just before radical cystectomy, and they received possible adjuvant chemotherapy or observation, according to the EAU guidelines after surgery. The primary data was presented in 2018 in the Journal of Clinical Oncology, where there was a complete response rate of approximately 40%.

The good thing from these updates is related to the survival outcomes, which are quite compelling, regardless of whether patients achieved the complete response, a major response, or a minor response, because overall the data were in favor of an event-free survival higher than 70% at 3 years. Most importantly, patients with the residual PT3, PT4, or PN+ disease, so a high-risk of residual disease, seem to have benefited the most from pembrolizumab with 3 year event-free survival or relapse-free survival estimates that were quite compelling compared to historical data.

Of course, we should wait for the results from the ongoing phase 3 studies, in particular, the KEYNOTE-905 study, which is currently testing pembrolizumab as a monotherapy or pembrolizumab-enfortumab vedotin combination therapy as compared to radical cystectomy up front, in patients who are cisplatin-ineligible.

The other point is related to the biomarkers because we confirmed the reliability of the Decipher classification as a molecular classification that highlights the fact that the patients with the claudin-low subtype, so the subtype with the basal subtype with the highest immune gene signature scores, benefited the most from neoadjuvant pembrolizumab and radical cystectomy. And that data were presented 2 years ago in Lancet Oncology.

Overall, quite promising data that put into the context of the ongoing data emerging from other similar phase 2 studies, all of these data suggest a potential role in the near future for neoadjuvant immune checkpoint inhibition before radical cystectomy in patients with muscle invasive bladder cancer. We currently have a label for adjuvant nivolumab in the patient with high-risk disease after radical cystectomy for PD-1 positive tumors. We will know from the ongoing phase 3 studies if the emerging data from the PURE-01 study and other similar studies, will set a new role for neoadjuvant immunotherapy in this patient population.

Source:

Basile G, Bandini M, Gidd EA, et al. Neoadjuvant pembrolizumab and radical cystectomy in patients with muscle-invasive urothelial bladder cancer: 3-year median follow-up update of PURE-01 trial. Clin Cancer Res. Published online October 18, 2022. doi:10.1158/1078-0432.CCR-22-2158