Impact of Molecular Profiling Offered to Patients with Metastatic Bladder Cancer in Early-Phase Clinical Trials - Expert Commentary

Early-phase clinical trials are a treatment option for patients with metastatic bladder cancer (mBC). However, Patients enrolled in these trials have already been exposed to toxicity from prior therapies and developed a poor performance status making it challenging to identify patients who are likely to benefit.

A recent study by Alhalabi et al. published in Molecular Cancer Research investigated the potential benefits of early-phase clinical trials to patients with mBC. The authors analyzed clinical and molecular data of 43 patients enrolled in phase I clinical trial at the University of Texas MD Anderson Cancer Center (MDACC) between June 2015 and September 2019. Twelve patients were enrolled in more than one trial, leading to a total of 57 trial participants (TPs). The median progression-free and overall survivals were 4.2 and 9.6 months, respectively. Across all TPs, the objective response rate (ORR) was 17.5%.

Out of the 41 patients with clinical NGS analysis, all but one patient harbored at least one somatic alteration. Among the most common actionable gene alterations were ERBB2 (n=12) and FGFR3 (n=14). Two out of four patients who received ERBB2-targeting therapy achieved partial response (PR), and one out of 9 patients who received FGFR3-targeting therapy achieved PR. Patients whose tumors harbored TP53 alterations were associated with shorter overall survival and lower ORR.  There was a trend toward worse immunotherapy (IO) treatment outcomes for patients with prior IO compared to IO-naïve.

This report highlights the potential clinical benefit of early-phase trials for patients with mBC, including potential objective responses. The availability of molecular profiling allowed the patients to receive the corresponding targeted agents. These insights could inform clinical decisions to offer early-phase clinical trials.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. Alhalabi O, Hahn AW, Msaouel P, Andreev-Drakhlin AY, Meric-Bernstam F, Naing A, et al. Molecular profiling of metastatic bladder cancer early-phase clinical trial participants predicts patient outcomes. Mol Cancer Res. 2021;19(3):395–402. PMID: 33323389

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