Neoadjuvant Nivolumab with or without Ipilimumab for Cisplatin-Ineligible Patients with Muscle-Invasive Bladder...

Area of Science:

• Oncology
• Immunotherapy
• Bladder Cancer Research

Background:

• Muscle-invasive bladder cancer (MIBC) presents treatment challenges, particularly for patients ineligible for standard cisplatin-based chemotherapy.
• Neoadjuvant immunotherapy offers a potential alternative for this patient population.

Purpose of the Study:

• To evaluate the safety and efficacy of neoadjuvant nivolumab, alone or in combination with ipilimumab, in cisplatin-ineligible patients with MIBC.
• To assess treatment response, including eligibility for cystectomy and pathological outcomes.

Main Methods:

• A phase II trial enrolled patients with MIBC into two cohorts: nivolumab alone and ipilimumab/nivolumab.
• The primary endpoint was eligibility for cystectomy within 60 days of treatment completion.
• Correlative analyses included gene expression profiling and comparison with the PURE-01 trial dataset.

Main Results:

• Nivolumab alone demonstrated good tolerability, with 12/15 patients eligible for cystectomy and a 13% pathological complete response (pCR) rate.
• The ipilimumab/nivolumab combination showed higher toxicity, delaying cystectomy in some patients, and resulted in lower pCR rates (7%).
• 12-month recurrence-free survival was 79% for nivolumab and 61% for ipilimumab/nivolumab. NCOR1 alterations and tumor-infiltrating immune cells showed potential associations with favorable outcomes.

Conclusions:

• Neoadjuvant nivolumab monotherapy is well-tolerated and shows potential in cisplatin-ineligible MIBC patients.
• The combination of ipilimumab and nivolumab exhibited significant toxicity, impacting surgical eligibility and suggesting limited efficacy in this unselected group.
• While neoadjuvant immunotherapy alone may not be sufficient for all patients, durable clinical complete responses were observed in some cases, warranting further investigation.