AUA 2017: Neoadjuvant sorafenib, gemcitabine, and cisplatin (SGC) for muscle-invasive urothelial bladder cancer (MIUBC): final results and translational findings of an open-label, single-arm, phase 2 study
Patients with clinically localized node-negative disease were enrolled and treated with 400mg sorafenib PO bid in addition to traditional GC chemotherapy for 4 cycles (12 weeks total). The primary endpoint was pT0 (which included pTis). 45 pts were enrolled. 38% had clinical stage T3 or T4. 58% had residual disease at cystectomy. 42% achieved pT0 (check this math). 53% had pT1. At 35 months follow up, neither median PFS nor OS was reached. Like prior studies, pathologic response was associated with improved outcomes (PFS and OS). Adverse events were modest with grade 3-4 hematologic complications as high as 29%, requiring temporary interruption in 53% of patients, and discontinuation in 10%.
Tumor samples were used for ERCC1-IHC and next-gen sequencing. ERCC1 positivity was associated with non-response. ERBB2/3 mutations were found only in responders. PIK3CA/AKT mutations were more frequent in non-responders. VEGF levels in the blood were not associated with survival outcomes.
This is a small preliminary study that offers proof of principle that the TKIs can be combined with cisplatin based neoadjuvant chemotherapy. Longer follow-up and more complete reporting in manuscript form will be necessary to better evaluate the risk/benefit profile of this additional therapy.
Presented by: Andrea Necchi
Contributed by: Jed Ferguson, MD/PhD and Ashish Kamat, MD. MD Anderson Cancer Center, Department of Urology.
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA