Dr McGregor on the Potential Use of Checkpoint Inhibitors in Rare GU Cancers

“We began] the development of [this program] years ago, and the idea was that we have a lot of patients who [present] with rare tumors or a rare variety of a common tumor, [such as] variants of bladder cancers [including] small cell or squamous cell [cancer] of the bladder or urinary tract. The idea was that immunotherapy is a tumor-agnostic approach that is approved across a variety of tumors.”

Bradley McGregor, MD, director, clinical research, Lank Center for Genitourinary Oncology; senior physician, Marra Lochiatto Investigator, Dana-Farber Cancer Institute (DFCI); assistant professor, medicine, Harvard Medical School, discusses the rationale for investigating the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for the treatment of patients with advanced rare genitourinary (GU) malignancies who had not previously received immunotherapy, as well as the process of implementing this regimen into the GU treatment paradigm at DFCI.

The rationale for investigating this immunotherapy regimen for patients with advanced rare GU malignancies stems from the unmet need for effective treatments in this population, particularly for patients with histological subtypes often excluded from traditional clinical trials, McGregor begins. These include patients presenting with rare GU malignancies or uncommon variants of common GU tumors, such as small cell or squamous cell carcinoma of the bladder or urinary tract, he expands.

Recognizing immunotherapy’s broad application across tumor types, McGregor and colleagues identified an opportunity to explore its efficacy in this niche population. In a phase 2 study (NCT03333616), through the DFCI rare GU tumor protocol, the combination of nivolumab and ipilimumab is being evaluated in 4 cohorts of patients with diverse diseasehistologies: bladder or upper tract carcinoma with variant histology, adrenocortical carcinoma, other rare genitourinary carcinomas, and any genitourinary carcinoma with neuroendocrine differentiation.

This trial’s protocol was designed to include patients often excluded from traditional trials, reflecting a commitment to expanding therapeutic options for rare GU malignancies, McGregor notes. By leveraging immunotherapy’s tumor-agnostic mechanism, the study aims to establish a foundation for incorporating checkpoint inhibitors into the treatment paradigms for rare and refractory GU cancers, he concludes.