Matthew Galsky, MD, professor of medicine and urology, Hematology and Medical Oncology, director of the Genitourinary Medical Oncology as well as the Novel Therapeutics Unit, and co-director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai, provides insight on potentially practice-changing studies in bladder cancer presented at the 2020 Genitourinary (GU) Cancers Symposium.
Several phase II studies with practice-changing potential were presented at the 2020 GU Cancers Symposium, says Galsky. For example, results from the phase II BLASST-1 trial, which evaluated neoadjuvant nivolumab (Opdivo), gemcitabine, and cisplatin in patients with muscle-invasive bladder cancer (MIBC) undergoing definitive cystectomy, showed a pathological complete response (pCR) rate of 49%. These data suggest that the addition of an immune checkpoint inhibitor to cisplatin-based chemotherapy, which has shown a significant benefit in progression-free survival in the metastatic setting, could also be of benefit in the neoadjuvant setting, says Galsky.
Data from the phase II NEODURVARIB trial are of particular importance because of the need for effective neoadjuvant treatments in cisplatin-ineligible patients, says Galsky. In the trial, investigators evaluated the combination of durvalumab (Imfinzi) and olaparib (Lynparza) in patients with MIBC prior to cystectomy. The results showed that the combination led to a 50% pCR rate in 10 patients, which compares favorably with historical rates observed with single-agent immunotherapy, says Galsky.
Additional data from the meeting showed limited activity with a PARP inhibitor in patients with metastatic disease who had previously received platinum-based chemotherapy. Investigators believe that the resistance mechanisms to PARP and platinum-based chemotherapy are similar, so it makes sense to evaluate the combination of a PARP inhibitor and a checkpoint inhibitor in patients who have not received prior platinum-based therapy, says Galsky.
At the 2019 ESMO Congress, the combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) led to an objective response rate (ORR) of more than 70% in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer enrolled in the phase Ib/II EV-103 trial. According to updated results presented at the symposium, these responses proved to be durable, says Galsky. At a median follow-up of 11.5 months, the ORR was 73%, including a 15.6%CR rate and a 57.8% partial response rate. The median duration of response had not been reached.
Furthermore, a phase III trial demonstrated the safety and efficacy of intravesical nadofaragene firadenovec in patients with high-grade, BCG-unresponsive, nonmuscle invasive bladder cancer. According to the findings, 53.4% of patients achieved a CR, and 45.5% remained free from recurrence at 1 year, suggesting that certain patients may be able to avoid cystectomy, concludes Galsky.