Commentary
Article
Author(s):
Antonio Cigliola, MD, discusses the evaluation of neoadjuvant sacituzumab govitecan in patients with muscle-invasive bladder cancer.
Investigators are hopeful that findings from the phase 2 SURE-01 (NCT05226117) and soon-expected phase 2 SURE-02 trial (NCT05535218) could help fill the significant unmet need that exists for patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC). Findings from SURE-01, which were presented at the 2024 ASCO Annual Meeting, evaluated neoadjuvant treatment with sacituzumab govitecan-hziy (Trodelvy) in this population. The latter trial, SURE-02 is testing perioperative therapy with sacituzumab govitecan and pembrolizumab (Keytruda) in the same population.
Interim results from the SURE-01 trial, presented by Antonio Cigliola, MD, and colleagues, showed that the pathological complete response (pCR) rate was 36.4% (95% CI, 14.9%-64.8%) among the 11 patients who underwent radical cystectomy after neoadjuvant treatment. The pCR rate was 47.6% (95% CI, 28.3%-67.6%) in the intention-to-treat (ITT) population. Safety profiles were closely monitored, with dose adjustments made after the first 8 patients experienced high rates of adverse effects (AEs).1,2
Expressing the need for continued investigation into the potential of this therapy, Cigliola noted, “As we look for better treatments, it is crucial to find effective alternatives for patients who cannot receive cisplatin.”
In an interview with OncLive®, Cigliola, a medical oncologist at San Raffaele Hospital in Milan, Italy, elaborated on the SURE-01 trial’s impact and future research directions, including the agent’s continued evaluation in combination with pembrolizumab in the ongoing phase 2 SURE-02 trial.
Cigliola: About 50% of patients with MIBC are cisplatin ineligible and for these patients radical cystectomy alone or chemoradiation remains the standard of care. We started this clinical trial with neoadjuvant sacituzumab govitecan for [these patients experiencing a] poor prognosis with the standard of care.
This is a phase 2 trial in which patients with cT2-4N0M0 MIBC who were ineligible for or refused cisplatin-based chemotherapy were scheduled to receive 4 cycles of neoadjuvant sacituzumab govitecan at 10 mg/kg intravenously on days 1 and 8, followed by radical cystectomy. The primary end point of this study [was the] pCR rate.
Eighteen patients received surgery after the neoadjuvant treatment. Eleven patients underwent radical cystectomy, and 7 patients refused radical cystectomy and chose a restage transurethral resection of bladder tumor [reTURBT]. The pCR rate was 36.4% in evaluable patients who underwent radical cystectomy. Among the ITT population of patients who received reTURBT or radical cystectomy the pCR rate was 47.6%, with pathological downstaging in 11 patients. Another interesting [finding] was that patients with residual disease had a circulating tumor DNA-negative test post-radical cystectomy.
After the initial 8 patients, the study was amended due to treatment-related AEs. Several cases of grade 3 or 4 neutropenia and diarrhea [were reported]. After the amendment, the treatment was well tolerated; 33.3% of all patients experienced a grade 3 AE and 19.1% experienced grade 4 AEs. The most common grade 3/4 AEs were neutropenia and diarrhea.
We are awaiting the results of the SURE-02 trial which is testing neoadjuvant pembrolizumab and sacituzumab govitecan followed by adjuvant pembrolizumab after radical cystectomy.
Our findings show that sacituzumab govitecan, which is used [to treat patients with] other types of cancers, such as breast cancer, [can also be used in] MIBC. With sacituzumab govitecan we can guarantee neoadjuvant treatment for patients who have a poor prognosis with the current standard of care.
I would like to have more clinical trials for these patients with MIBC. It could be very interesting to have new clinical trials with the bladder-saving approach for patients with MIBC in which we can consider the possibility of having clinical complete response as a primary end point instead of pCR.