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Patients with muscle-invasive bladder cancer who were treated with presurgical chemotherapy may have a 55% lower risk of death, research shows.
Patients with muscle-invasive bladder cancer who are not eligible or refuse to receive presurgical gemcitabine chemotherapy demonstrated responses to TAR-200 with cetrelimab, findings from a phase 2 study showed, as presented at the 2024 ESMO Congress.
TAR-200 is a type of drug delivery system that helps sustain the release of gemcitabine chemotherapy into the bladder, according to Johnson & Johnson.
Cetrelimab is a type of monoclonal antibody which binds certain targets in the body to help the immune system destroy cancer cells, as the National Cancer Institute defines.
Study highlights:
In the phase 2 SunRISe-4 study, a total of 122 patients with muscle-invasive bladder cancer who were scheduled for radical cystectomy (surgical removal of the bladder) and were ineligible for or refused presurgical chemotherapy were randomly assigned to two groups.
The first group included 79 patients who were treated with TAR-200, gemcitabine chemotherapy and cetrelimab. The second group included 41 patients who received cetrelimab alone. A total of 53 patients in the TAR-200 combination group and 31 patients in the cetrelimab alone group were determined evaluable for efficacy.
“SunRISe-4 demonstrates for the first time a benefit of the addition of TAR-200, an intravesical targeted releasing system, to checkpoint inhibition as presurgical treatment in patients with MIBC,” Dr. Andrea Necchi of IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, in Milan, Italy, said in a late-breaking oral presentation of the data.
Treatment with TAR-200 plus cetrelimab in 53 patients led to a pathologic complete response (pCR; complete disappearance of cancer) rate of 42% and a pathologic overall response (pOR; percentage of patients whose cancer shrunk or disappeared) rate of 60% in the efficacy-evaluable population of patients with cT2 to cT4a disease. Treatment of cetrelimab alone in 31 patients, which was also evaluated, led to respective pCR and pOR rates of 23% and 36%.
For patients with MIBC who have T2 to T4a N0M0 disease, the standard-of-care treatment approach is to undergo radical cystectomy with or without presurgical cisplatin-based chemotherapy (such as gemcitabine), but up to half of patients are eligible for chemotherapy. Approximately 50% of patients who undergo radical cystectomy will have their cancer return within two years. After the procedure, the five-year survival rates are still low, at about 50%, Necchi said.
“Also, in patients with MIBC undergoing radical cystectomy, we know that pathological stage is prognostic (the likelihood) for survival,” he added. With the procedure alone, pCR rates range from 10% to 15%; with presurgical chemotherapy, the pCR rate rose to approximately 30%; and with presurgical checkpoint inhibition, the pCR rates fell between 31% and 39%.
The achievement of pCR in patients who have received presurgical chemotherapy has been linked with a 55% lower risk of death and an 81% lower recurrence risk versus those who have residual disease. “There is a high unmet need for more tolerable treatment options for patients with MIBC who are candidates for radical cystectomy, but not candidates for or who refuse presurgical chemotherapy,” Necchi underscored.
Phase 1 data have demonstrated TAR-200’s clinical activity in patients with muscle-invasive bladder cancer.
The main goal of the trial was pCR, and secondary goals included recurrence-free survival (living without the cancer returning) and safety. Exploratory goals included pOR, overall survival (time patients live, regardless of their disease status), time to symptomatic progression, quality of life and biomarker analysis.
Necchi said that the main baseline characteristics between the groups were “pretty well balanced.” Regarding presurgical chemotherapy, 39.2% of those in the combination group were ineligible and 60.8% refused it, and in the cetrelimab alone group, these respective rates were 36.6% and 63.4%. In the combination group, 20.3% of patients had visible residual disease before starting therapy, and this was also true for 14.6% of those in the cetrelimab alone group. Regarding tumor stage in the combination group, 78.5% had cT2 disease and 21.5% had cT3-cT4a disease; these rates were 85.4% and 14.6%, respectively, in the cetrelimab alone group. Further, 20.3% and 26.8% of patients had urothelial carcinoma with variant histology. “There are [also] a few patients with a history of intravesical therapy, in general meaning, a history of previous non-muscle-invasive disease progressing to muscle-invasive disease,” Necchi said.
Regarding safety, at least one treatment-related side effect of any severity was experienced by 72.2% of those in the combination group and 43.9% of those in the cetrelimab alone group. The most common treatment-related side effects in these respective groups were dysuria (painful or uncomfortable urination; 27.8%; 18.3%), pollakiuria (frequent urination; 27.8%; 18.3%), micturition urgency (sudden and strong urge for urination; 15.2%; 10%) and hematuria (blood in urine; 13.9%; 9.2%).
Treatment-related side effects that were grade 3 (severe) or worse were reported in 11.4% of those in the combination group and 4.9% of those in the cetrelimab alone group. Serious treatment-related side effects occurred in 11.4% of those in the combination group and 2.4% of those in the cetrelimab alone group. Treatment-related side effects led to discontinuation of TAR-200 in 8.9% of patients and cetrelimab discontinuation in 7.6% of patients — all in the combination group. One patient in the cetrelimab alone group experienced a treatment-related side effect that proved fatal.
Grade 3 or worse immune-related toxicities were experienced by 6.3% of those in the combination group and 4.9% of those in cetrelimab alone group. The median time to radical cystectomy in the respective groups was 13.7 weeks and 12.6 weeks.
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