ASCO 2019: Phase II Study of Nivolumab and Ipilimumab for Advanced Bladder Cancer of Variant Histologies - Medical Oncologist Perspective

Chicago, IL ( Combination ipilimumab/nivolumab (ipi/nivo) has seen success in melanoma, MSI high colorectal cancer, and renal cell carcinoma (RCC).1 In urothelial carcinoma, CheckMate 032 evaluated the efficacy of ipi/nivo in an open-label, multicenter, phase I/II study where ipi/nivo was given at two different dose cohorts (Ipi-1/Nivo-3, and Ipi-3/Nivo-1). Patients were eligible if they had progressed on one or more prior lines of platinum-based chemotherapy and the primary endpoint was objective response rate by RECIST 1.1. Twenty-six patients received Nivo-1/Ipi-3 and 104 patients received Nivo-3/Ipi-1 and the objective response rate was 38.5% in the Nivo-1/Ipi-3 arm and Nivo-3/Ipi-1 arm.   For patients with non-urothelial bladder cancer, it is unknown if ipi/nivo is effective. This study evaluates nivolumab and ipilimumab for advanced bladder cancer of variant histologies (BCVH).

ASCO 2019 nivo bladder endpoints

This abstract provides data on 19 patients with BCVH. Patient characteristics are below.

ASCO 2019 nivo bladder patient characteristics tab 1

The variant histologies which were represented included squamous cell carcinoma (n=6), small cell carcinoma (n=3), adenocarcinoma (n=3), urachal (n=5), plasmacytoid (n=1), and spindle cell carcinoma (n=1).

ASCO 2019 nivo bladder dist of subtypes pie chart

After a median follow-up of 3.6 months, the objective response rate was 37% (small cell – 2, urachal – 1, and plasmacytoid – 1).

ASCO 2019 nivo bladder breakdown of ORR

In terms of safety, 16% (3/19) patients developed grade 3 treatment-related toxicity and 1 patient had grade 4 toxicity. Fatigue, rash, and hypothyroidism were the most common adverse events (AEs) overall.

ASCO 2019 nivo bladder Adverse events

Urothelial bladder cancer represents >90% of all bladder cancer diagnoses in the United States and a number of immunotherapy trials have changed the way we manage urothelial carcinoma over the past few years. However, for patients with non-urothelial bladder cancer, much is unknown regarding the efficacy of immunotherapy. One prior case report described a patient with squamous cell carcinoma who had a complete response to pembrolizumab.2 This abstract demonstrates that the combination of ipi/nivo may be an effective treatment for patients with bladder cancer of variant histologies.

Presented by: Bradley Alexander McGregor, MD, Chair, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu, at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

  1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. New England Journal of Medicine 2018;378:1277-90.
  2. Kao C, McNamara M, Alley C, et al. A Complete Response After Pseudo-progression: Pembrolizumab for Metastatic Squamous Cell Carcinoma (SCC) of the Bladder. Clinical genitourinary cancer 2019.