Results from the IMMUNOPRESERVE clinical trial reveal a promising bladder-preserving approach for patients with localized muscle-invasive bladder cancer (MIBC), combining radiation therapy with dual checkpoint inhibition. The findings, published in Clinical Cancer Research, demonstrate significant potential for improving patient quality of life while maintaining therapeutic efficacy.
Innovative Treatment Approach Shows High Response Rates
The multicenter, phase II trial evaluated the combination of radiation therapy with two immune checkpoint inhibitors - durvalumab (targeting PD-L1) and tremelimumab (targeting CTLA-4). Among 28 evaluable patients, an impressive 93% achieved complete response, with 30 out of 32 patients successfully preserving their bladders after a median follow-up of 27 months.
The treatment protocol involved three courses of durvalumab plus tremelimumab administered four weeks apart, concurrent with radiotherapy. The two-year overall survival rate reached 84%, with a distant metastasis-free survival rate of 83%.
Alternative to Radical Cystectomy
"Radical cystectomy is a highly invasive surgery that can significantly impact patients' quality of life," explains Dr. Xavier Garcia-del-Muro, professor of medical oncology at the University of Barcelona and senior author of the study. He notes that patients often struggle with complications from urostomy bags and reconstructed neobladders following traditional surgery.
The new approach offers particular promise for patients who are either ineligible for or refuse cystectomy. Unlike conventional chemotherapy-based treatments, which can be associated with significant toxicity and exclude up to half of potential patients, this immunotherapy combination showed a manageable safety profile.
Safety Profile and Treatment Outcomes
The treatment regimen demonstrated acceptable tolerability, with 31% of patients experiencing grade 3 or 4 adverse events. While eight patients (25%) could not complete the third planned dose of immunotherapy due to treatment-related toxicity, and one treatment-related death was reported, investigators considered the overall safety profile favorable.
Disease recurrence patterns showed that after two years of follow-up:
- 16% experienced metastatic recurrence
- 19% had recurrence of muscle-invasive disease
- 3% developed non-muscle invasive disease
- Only two patients required radical cystectomy due to recurrence
Scientific Rationale and Mechanism
The combination approach leverages the synergistic effects between radiation and immunotherapy. Dr. Garcia-del-Muro explains that radiotherapy can trigger cancer cells to release danger signals and cytokines that stimulate the immune system, potentially enhancing the effectiveness of immune checkpoint inhibitors.
While the researchers acknowledge limitations including the small sample size and relatively short follow-up period, they plan to validate these findings in larger studies with extended follow-up and direct comparisons to other treatment regimens, including radiation plus chemotherapy.
"While this is an early exploratory study, the results are encouraging and highlight the potential of radiotherapy plus combination immunotherapy to improve quality of life without compromising survival," concludes Dr. Garcia-del-Muro.
