Neoadjuvant gosatuzumab shows activity in muscle-invasive bladder cancer, but questions remain

Neoadjuvant treatment with sacituzumab govitecan after surgery in patients with muscle-invasive bladder cancer (MIBC) demonstrated post-operative complete responses following a protocol revision that included dose reduction and G-CSF prophylaxis, according to findings from the phase 2 SURE-01 trial (NCT05226117). Some patients who meet strict criteria for clinical complete response [cCR] have chosen a bladder-sparing approach, demonstrating the potential for cure.

In the design of the study, patients were intended to receive 4 cycles of 10 mg/kg of gosatuzumab on days 1 and 8 every 3 weeks; however, after the initial 8 patients were enrolled in the study, the protocol was modified to address the high toxicity rate. Overall, grade 3/4 neutropenia was observed in 75% of the first 8 patients, and 50% also experienced grade 3/4 diarrhea. In addition, there was 1 treatment-related death due to sepsis. According to the amendment, the regimen dose of gosatuzumab was changed to 7.5 mg/kg, and G-CSF was introduced as primary prophylaxis starting on day 9 of the first cycle. Those with 3 or more risk factors for febrile neutropenia were excluded from the study.

In total,21 patients with a median age of 71 years participated in the study. One-third of patients had cT3-4N0 disease at baseline, and nearly half (47.6%) had mixed variant histology in addition to urothelial carcinoma. The primary endpoint was pathological complete response rate (ypT0N0). Secondary endpoints examined event-free survival (EFS), overall survival (OS), safety and quality of life. UGT1A1 gene testing has also been completed.

Patients were screened at baseline using MRI of the pelvisand were reviewed using MRI after neoadjuvant gosatuzumab. Patients with cCR or those who did not elect to undergo radical cystectomy were allowed the option of transurethral resection of bladder tumors (TURBT) and were followed up for observation. Overall, 18 of 21 enrolled patients completed neoadjuvant gosatuzumab and went on to surgery. Among them, 11 cases chose radical cystectomy and 7 cases chose TURBT. Among patients who refused cystectomy, the reason was 6 cCR and 1 patient decision. One patient had worsening/recurrence before surgery. The time between gosatuzumab and surgery was 6.9 weeks (range, 4.3-9.9 weeks).

In patients undergoing radical cystectomy (n=11), 4 patients had ypT0N0 (36.4% of patients; 95% CI, 14.9%-64.8%). A ypT ≤1N0 result was observed in 5 patients (45.4%; 95% CI, 21.2%-72.0%). In the entire intention-to-treat population (n=21), 10 patients had a surgical outcome of ypT0N0 (47.6%; 95% CI, 28.3%-67.6%). One patient decided to undergo TURBT despite evidence of residual disease after neoadjuvant gosatuzumab, turned out to be ypT2Nx, and received subsequent chemotherapy plus radiation.

Among patients who received gosatuzumab CCR and chose TURBT over cystectomy, the majority went on to receive cCR after TURBT (6 of 7). Those who continued to respond were negative on cystoscopy and the Signatera circulating tumor DNA test. These people are currently under observation. One patient in the initial cCR group elected TURBT, and the surgical result was ypT2Nx, with positive cystoscopy and ctDNA testing. The man went on to receive chemotherapy plus radiation.

Of the 21 enrolled patients, 81% experienced adverse events of any grade, the most common being diarrhea (42.9%), anemia (42.8%), alopecia (38.1%), and neutropenia (33.3%). The most common grade 3/4 event was neutropenia, with an incidence of 9.5% for grade 3 and 19.1% for grade 4. Grade 3 diarrhea occurred in 23.9% of patients.

Treatment-related AEs (TRAEs) leading to dose interruption occurred in 19.0% of patients, occurring only in patients receiving the 10 mg/kg dose. There were no dose interruptions in patients who received primary prophylaxis with gosatuzumab and G-CSF at a dose of 7.5 mg/kg. There was 1 dose reduction in the 7.5 g/kg group related to grade 3 treatment-related neutropenia.