Necchi A, et al. - Researchers designed an open-label, single-arm, single-center, phase 2 study which indicated that Sorafenib was combined with gemcitabine and cisplatin chemotherapy (SGC) combination was active in muscle-invasive urothelial bladder carcinoma (MIUBC), and the distinguished molecular features included alterations that may help personalize treatment in MIUBC with new more potent targeted agents, combined with chemotherapy.

Methods

• T2–T4a N0 patients received four cycles of SGC followed by cystectomy after transurethral resection of the bladder.
• In this study, sorafenib 400 mg q12h daily, continuously, was added to standard GC chemotherapy.
• The preliminary outcome was the pathologic complete response (pT0), assuming H0: ≤0.20 and H1: ≥0.40, with a type I and type II error of 5% and 10%, respectively.

Results

• They recruited a total of 46 patients between April 2011 to June 2016.
• They observed pathologic T0 response in 20 patients (43.5%, 95% CI: 28.9–58.9); pT ≤ 1 in 25 (54.3%, 95% CI: 39.0–69.1).
• They found that the median progression-free survival was not reached (NR, interquartile range: 23.6–NR), nor was median overall survival (interquartile range: 30.3–NR) after a median follow-up of 35 months,.
• The data indicated that hematologic and extrahematologic grade 3 to 4 adverse events occurred in 45.6% and 26.1% of patients, respectively.
• They exhibited evidence that in 29 samples from responders (pT ≤ 1) and nonresponders, different distribution of missense mutations involved DNA-repair genes, RAS-RAF pathway genes, chromatin-remodeling genes, and HER-family genes.
• The evidence showed that ERCC1 immunohistochemical expression was correlated with pT ≤ 1 response (P = 0.047).
• Remarkably, the absence of a comparator arm prevented us to quantify sorafenib contribution.