Neoadjuvant Sacituzumab Govitecan Data Draw Curiosity in Cisplatin-Ineligible MIBC

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.

OncLive: What are some unmet needs that exist for patients with MIBC? How did the SURE-01 trial seek to address some of those needs?

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.

What was the design of the SURE-01 trial?

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.

What were some of the interim efficacy findings that were presented at ASCO?

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.

What is the safety profile of this regimen?

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.

What are the next steps for this research?

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.

What are some of the potential clinical implications of this research?

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.

Looking more broadly at bladder cancer research, what future research endeavors would you like to see?

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.

References

1. Cigliola A, Moschini M, Tateo V, et al. Perioperative sacituzumab govitecan (SG) alone or in combination with pembrolizumab (pembro) for patients with muscle-invasive urothelial bladder cancer (MIBC): SURE-01/02 interim results. J Clin Oncol. 2024;42(suppl 17):LBA4517. doi:10.1200/JCO.2024.42.17_suppl.LBA4517
2. Sacituzumab govitecan, preceding radical cystectomy, in treating patients with muscle-invasive bladder cancer. ClinicalTrials.gov. Updated February 23, 2022. Accessed July 7, 2024. https://www.clinicaltrials.gov/study/NCT05226117