Presentation Authors: Nima Almassi*, Eugene Pietzak, Samuel Funt, Aleksandra Walasek, Nikolaus Schultz, Guido Dalbagni, Bernard Bochner, Hikmat Al-Ahmadie, Min Yuen Teo, Dean Bajorin, Jonathan Rosenberg, Gopa Iyer, David Solit, New York, NY
Introduction: Genomic alterations predicting response to targeted therapy are an area of active interest in developing novel therapies for patients with metastatic urothelial carcinoma (mUC) progressing after first and second-line therapy. With the objective of characterizing the frequency of actionable alterations and the evidence supporting therapy targeting these alterations, we report our experience with next-generation sequencing in mUC.
Methods: Patients with sequenced mUC lesions were identified from our prospectively-maintained institutional database. All actionable alterations with clinical or biologic evidence supporting an association with response to targeted therapy were identified and stratified by OncoKB level of evidence. The relationship between strength of evidence and administration of targeted therapy was examined.
Results: Ninety-nine of 134 patients (74%) harbored at least one actionable alteration, with 162 total actionable alterations identified. Twenty level 2B alterations were identified, reflecting alterations predictive of response to an FDA-approved drug in another indication, with ERBB2 amplification (9), TSC1/TSC2 (6), and BRCA1/BRCA2 mutations (3) most common. Twenty-eight level 3A and 51 level 3B alterations were identified, reflecting compelling clinical evidence supporting targeted therapy in bladder cancer and non-bladder cancer indications, respectively. Sixty-two level 4 alterations, supported by compelling biologic evidence, were also identified. Seventeen patients received targeted therapy, which was administered to 21% of patients with level 3B or higher alterations (figure).
Conclusions: Most mUC lesions harbor at least one actionable alteration, which may serve as rational targeted therapeutic opportunities in mUC. These findings highlight the need for additional clinical trials and the role of genetic testing in identifying candidates for targeted therapy.
Source of Funding: This work was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, the Michael and Zena Wiener for Therapeutics Program in Bladder Cancer, Pin Down Bladder Cancer, Cycle for Survival, the Marie-Josee and Henry R. Kravis Center for Mole