Gemcitabine Intravesical System Shows Promise in BCG-Unresponsive Bladder Cancer, Reducing Need for Radical Cystectomy
Key Insights
Johnson & Johnson's INLEXZO (search) (gemcitabine intravesical system) demonstrated an 82.4% complete response rate in patients with BCG-unresponsive, high-risk non-muscle invasive bladder cancer with carcinoma in situ.
The treatment achieved 74.3% disease-free survival at one year in patients with papillary-only disease, with 92.3% of patients avoiding radical cystectomy.
Phase 2b SunRISe-1 trial results show the therapy may offer a bladder-sparing alternative for patients who traditionally faced life-altering surgical removal of the bladder.
Johnson & Johnson's INLEXZO (search) (gemcitabine intravesical system) has demonstrated significant efficacy in treating patients with BCG-unresponsive, high-risk non-muscle invasive bladder cancer (NMIBC), potentially offering a bladder-sparing alternative to radical cystectomy. New data from the Phase 2b SunRISe-1 trial presented at the Society of Urologic Oncology Annual Meeting show promising results across multiple patient populations.
High Complete Response Rates in CIS Patients
In the study's cohort 2, which included 85 patients with carcinoma in situ (CIS), the gemcitabine intravesical system achieved an 82.4% complete response (CR) rate. Of the 70 patients who achieved a complete response, 37 (52.9%) maintained their response for 12 months or longer. The median follow-up for this cohort was 20.2 months, with a range of 2-48 months.
"[Gemcitabine intravesical system] monotherapy is associated with a high CR rate and durable responses, with minimal risk of disease progression to a more advanced (T2 or higher) disease stage," the study authors noted.
Significant Disease-Free Survival in Papillary-Only Disease
Cohort 4 of the SunRISe-1 study focused specifically on 52 patients with papillary-only, high-risk NMIBC whose disease did not respond to BCG therapy. At a median follow-up of 15.9 months, the one-year disease-free survival rate was 74.3% (95% CI, 59.2-84.6), meaning nearly three out of four patients remained free from cancer recurrence.
"The findings are meaningful, as the majority of patients remained free of cancer recurrence at one year despite having papillary tumors that carry a high risk for recurrence and a significant risk of progression to a more aggressive, muscle-invasive stage of disease," said Siamak Daneshmand, M.D., Professor of Urology at the University of Southern California and presenting author.
Results were consistent across different tumor stages, with 74.8% disease-free survival for high-grade Ta tumors and 74.1% for T1 papillary tumors. Additionally, progression-free survival was 95.6% at one year, and overall survival reached 98%.
Reduced Need for Radical Cystectomy
One of the most significant findings was the substantial reduction in the need for radical cystectomy. In cohort 2, only 18 (21.2%) of the 85 patients required radical cystectomy, with 12 (14.1%) of these being initial responders. The estimated radical cystectomy-free rates were 86.6% at 12 months and 75.5% at 24 months.
For the papillary-only disease cohort, 92.3% of patients did not undergo radical cystectomy, and the median time to cystectomy was not reached.
"Bladder removal has traditionally been the primary path forward for these patients, a life-altering procedure that can have a significant impact on a patient's quality of life," Daneshmand explained.
Disease Progression and Safety Profile
The treatment showed a low rate of disease progression to more advanced stages. Only seven (8.2%) patients in cohort 2 progressed to T2 or higher disease. Of the 41 patients who experienced disease persistence, progression, or recurrence, the majority had persistence or recurrence of high-risk NMIBC rather than progression to muscle-invasive disease.
The therapy was generally well-tolerated across both cohorts. In the papillary-only disease group, most patients (80.8%) experienced treatment-related side effects that were low grade, such as mild urinary symptoms including burning, frequency, or urgency. More serious side effects occurred in 13.5% of patients and most often involved bladder pain. Only 7.7% of patients discontinued treatment due to side effects, and no treatment-related deaths were reported.
Treatment Protocol and Future Directions
The gemcitabine intravesical system was administered every three weeks for the first 24 weeks, followed by every 12 weeks through week 96. The treatment maintained patients' Overall Health Status and Physical Functioning scores during therapy.
These results support continued evaluation in the ongoing Phase 3 SunRISe-5 study, which is comparing the gemcitabine intravesical system to chemotherapy in patients with previously BCG-treated, papillary-only NMIBC.
"At Johnson & Johnson, we are committed to developing innovative treatments for patients with high-risk NMIBC who have few options beyond life-altering surgery," said Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Johnson & Johnson Innovative Medicine.
The FDA has already approved INLEXZO (search) for the treatment of adult patients with BCG-unresponsive, non-muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors, making it an available option for this challenging patient population.