In a groundbreaking phase 2 study (NCT03333616), researchers explored the efficacy of combining nivolumab (Opdivo) and ipilimumab (Yervoy) for treating advanced rare GU malignancies in patients who had not previously received immunotherapy. The study, led by Bradley McGregor, MD, demonstrated an objective response rate (ORR) of 37% among patients with bladder cancer with variant histologies (BCVH), with a median duration of response not yet reached and nine patients experiencing responses lasting over 12 months. The median progression-free survival was 6.2 months, and the 12-month overall survival rate stood at 58%.
McGregor highlighted the significance of enrolling 49 patients with BCVH in less than 3 to 4 years, a feat achieved despite the challenges posed by the COVID-19 pandemic. He emphasized the importance of collaboration with patients, advocacy groups, and multiple sites to advance care for those with rare tumors.
The study's rationale stemmed from the need to address rare tumors or rare varieties of common tumors, such as variants of bladder tumors, through a tumor-agnostic approach like immunotherapy. The research focused on a wide range of tumor types, including adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and small cell prostate cancer, to identify the most effective treatment strategies.
Early efficacy signals were observed, particularly in patients with divergent histology of the urinary tract, where a response rate close to 40% was noted. Impressive responses were also seen in patients with small cell carcinoma of the bladder, leading to further expansion of the study to include over 50 patients with diverse histologies of the urinary tract, confirming the initial findings.
McGregor and his team are now working on publishing the manuscript, with a focus on biomarker response, including PD-L1, to guide future therapy for patients with these rare tumors. This study represents a significant step forward in the treatment of rare GU cancers, offering hope for patients seeking novel and effective therapeutic options.
