Dr Cigliola on Potential Implications of the SURE-01 and SURE-02 Trials in MIBC

Antonio Cigliola, MD, medical oncologist, IRCCS San Raffaele Hospital, discusses potential clinical implications of data from the phase 2 SURE-01 study (NCT05226117), as well as anticipated data from the phase 2 SURE-02 trial (NCT05535218), for patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC).

The SURE-01 trial investigated the use of neoadjuvant sacituzumab govitecan-hziy (Trodelvy) in patients with MIBC, Cigliola begins. Patients in this population historically have limited treatment options, particularly those ineligible for cisplatin, he notes. 

, revealed a pathological complete response (pCR) rate of 36.4% (95% CI, 14.9%-64.8%) among the 11 patients who underwent radical cystectomy following neoadjuvant treatment. In the intention-to-treat population, the pCR rate was 47.6% (95% CI, 28.3%-67.6%).

These results indicate that sacituzumab govitecan, which has been effective in treating patients with other cancers such as breast cancer, also holds promise for patients with MIBC who face poor prognoses with current standard treatments, Cigliola states. Importantly, the trial monitored safety profiles closely, with dose adjustments implemented after the first 8 patients experienced high rates of adverse effects, he details. This careful management underscores the potential of sacituzumab govitecan as a viable neoadjuvant option in MIBC, Cigliola emphasizes.

Looking ahead, investigators are optimistic that the findings from SURE-01, along with forthcoming data from the SURE-02 trial, could significantly impact the treatment landscape for cisplatin-ineligible MIBC patients, Cigliola says. The SURE-02 trial is evaluating perioperative therapy with sacituzumab govitecan in combination with pembrolizumab (Keytruda), followed by adjuvant pembrolizumab after radical cystectomy. If successful, this combination approach may offer a new therapeutic strategy for a patient population that currently has few effective options, he concludes.

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Antonio Cigliola, MD, discusses potential clinical implications of data from the phase 2 SURE-01 and SURE-02 trials in MIBC.

Dr Cigliola on the Safety Findings from the SURE-01 Study in MIBC

Antonio Cigliola, MD, medical oncologist, IRCCS San Raffaele Hospital, discusses 

findings from the phase 2 SURE-01 study (NCT05226117)

, which evaluated neoadjuvant sacituzumab govitecan-hziy (Trodelvy) in patients with muscle-invasive bladder cancer (MIBC). Notably, these data were shared at the 

Several unmet needs remain for patients with MIBC, particularly for those who are ineligible for cisplatin chemotherapy, Cigliola begins. He shares that approximately 50% of patients with MIBC fall into this category, leaving radical cystectomy or chemoradiation as the standard treatment options. Recognizing the poor prognosis associated with these treatments, the SURE-01 trial was initiated to explore the efficacy of neoadjuvant sacituzumab govitecan in this patient population, Cigliola explains.

The SURE-01 trial is a phase 2 clinical study

 designed for patients with cT2-4N0M0 MIBC who either could not receive or refused cisplatin-based chemotherapy, he continues. Participants were administered 4 cycles of neoadjuvant sacituzumab govitecan at a dose of 10 mg/kg intravenously on days 1 and 8, followed by a radical cystectomy. The primary end point of this study was to determine the pathological complete response rate, Cigliola elucidates.

Initially, the study reported treatment-related adverse events (AEs), leading to a protocol amendment after the first 8 patients were treated. Prior to the amendment, several cases of grade 3 or 4 neutropenia and diarrhea were observed, according to Cigliola. Post-amendment, the treatment regimen was well tolerated. Overall, 33.3% of patients experienced grade 3 AEs, and 19.1% of patients experienced grade 4 AEs, with neutropenia and diarrhea being the most common severe AEs, Cigliola shares.

In conclusion, the SURE-01 trial demonstrates promising interim efficacy results with sacituzumab govitecan as a neoadjuvant treatment in cisplatin-ineligible patients with MIBC, with a manageable safety profile post–study amendment, he reports. These findings may pave the way for new treatment approaches in this challenging-to-treat patient population, Cigliola concludes.

Antonio Cigliola, MD, discusses the phase 2 SURE-01 study of neoadjuvant sacituzumab govitecan in muscle-invasive bladder cancer.

Dr Cigliola on the Background of the SURE-01 Study in MIBC

Dr Cigliola on the Efficacy of Sacituzumab Govitecan in MIBC

Antonio Cigliola, MD, medical oncologist, IRCCS San Raffaele Hospital, discusses interim efficacy findings from the phase 2 SURE-01 study (NCT05226117) investigating neoadjuvant sacituzumab govitecan-hziy (Trodelvy) in patients with muscle-invasive bladder cancer (MIBC).

Of the 38 patients who were enrolled onto SURE-01, 31 received neoadjuvant sacituzumab govitecan and 18 completed all 4 cycles of treatment. In total, 21 efficacy-evaluable patients comprised the intention-to-treat (ITT) population, and 11 patients underwent radical cystectomy. Seven patients refused to undergo radical cystectomy after displaying evidence of clinical complete response (CR; n = 6) or according to patient decision (n = 1); these patients received repeat transurethral resection of their bladder tumors. The median duration of treatment was 11.7 weeks (range, 0.4-16.4), and the median time from the end of sacituzumab govitecan therapy to surgery was 6.9 weeks (range, 4.3-9.9).

At a median follow-up of 7.1 months, patients who underwent radical cystectomy had a pathologic CR (pCR) rate of 36.4% (95% CI, 14.9%-64.8%). In the ITT population, the pCR rate was 47.6% (95% CI, 28.3%-67.6%), and 11 patients had pathological downstaging.

Furthermore, all patients with residual ypT3 to ypT4N0 or ypTanyN-positive disease following treatment with sacituzumab govitecan were circulating tumor DNA (ctDNA)–negative after radical cystectomy, Cigliola says. The remaining ctDNA analyses of pre- and post-therapy biomarker associations are ongoing and immature.

Regarding safety, the most common any-grade treatment-related adverse effects (TRAEs) were anemia (42.8%), neutropenia (33.3%), thrombocytopenia (4.8%), diarrhea (42.9%), nausea (14.3%), vomiting (4.8%), alopecia (38.1%), cutaneous AEs (4.8%), hematuria (4.8%), urinary tract infections (4.8%), creatinine increases (9.5%), sepsis (14.3%), and fatigue (28.6%). The most common grade 3/4 TRAEs were anemia (grade 3, 4.8%; grade 4, 0%), neutropenia (9.5%; 19.1%), diarrhea (23.9%; 0%), increased creatinine (9.5%; 0%), and sepsis (0%; 9.5%). One instance of grade 5 sepsis was observed.

Notably, the phase 2 SURE-02 trial (NCT05535218) is evaluating sacituzumab govitecan plus pembrolizumab (Keytruda) followed by adjuvant pembrolizumab in patients with MIBC.

Antonio Cigliola, MD, discusses interim efficacy data from the SURE-01 study investigating neoadjuvant sacituzumab govitecan in patients with MIBC.

Antonio Cigliola, MD

Articles

Dr Cigliola on Potential Implications of the SURE-01 and SURE-02 Trials in MIBC

Dr Cigliola on the Background of the SURE-01 Study in MIBC

Dr Cigliola on the Efficacy of Sacituzumab Govitecan in MIBC