Dr. Syed Hussain et al. hypothesized that the addition of nintedanib to GC could improve outcomes in patients with locally advanced muscle-invasive bladder cancer. To test this hypothesis, Hussain et al. performed a phase II randomized placebo-controlled neoadjuvant trial to determine whether nintedanib used in combination with standard treatment (GC) improves outcomes in patients with locally advanced muscle-invasive bladder cancer compared to standard treatment (GC) alone. nintedanib is an orally available, potent, small molecule triple kinase inhibitor. The primary outcomes were pathological response rate and overall complete response rate. The secondary outcomes were progression-free and overall survival at 12 and 24 months.
The study design is depicted:
There were 120 patients enrolled in the study across 15 institutions. With regards to primary outcomes, of 86 evaluable patients, there was no difference in pathological complete response rate by intention to treat (21/57 [37%] in nintedanib group versus 20/63 [32%] in placebo group). Of the 109 evaluable patients, there was no difference in overall complete response rate by intention to treat (22/57 [38%] in nintedanib group versus 25/63 [39%] in placebo group).
With regards to secondary outcomes, patients in the nintedanib group had improved progression-free survival at 12 and 24 months (12 months: 89% in nintedanib group versus 74% in placebo group, 24 months: 82% in nintedanib group versus 61% in placebo group, p=0.013). Patients in the nintedanib group also have improved overall survival at 12 and 24 months (12 months: 96% in nintedanib group versus 83% in placebo group, 24 months: 89% in nintedanib group versus 69% in placebo group, p=0.018).
With regards to toxicity, there was no difference in patients with [Symbol]grade 3 adverse events (36/57 [63%] in nintedanib group versus 37/63 [59%] in placebo group). However, patients in the nintedanib group had a higher incidence of grade 3-4 neutropenia (6/57 [11%] in nintedanib group versus 1/63 [2%] in placebo group, p=0.052).
Dr. Syed Hussain et al. concluded that the nintedanib group failed to demonstrate an improvement in pathological response rate and overall complete response. However, patients treated with ninetedanib in combination with GC demonstrated an improvement in progression-free and overall survival at 12 and 24 months. Importantly, the utilization of nintedanib in combination with GC was associated with a good safety profile. Given these promising data, Dr. Hussain emphasized the importance of conducting Phase III trials to further characterize the efficacy of utilizing nintedanib in combination with GC.
Presented by: Syed A. Hussain, MD, University of Sheffield, Academic Unit of Oncology, Department of Oncology and Metabolism, Sheffield, United Kingdom
Written By: Ziho Lee, MD, Fellow in Advanced Robotic Oncology and Reconstruction, Temple University, Philadelphia, PA, Twitter: @ZLeeGU at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California