Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: A randomized phase II study of the Sarah Cannon Research Institute.

Abstract

5513 Background: The combination of paclitaxel and carboplatin is the most widely used chemotherapy regimen for patients (pts) with advanced ovarian cancer, producing a median survival of approximately 36 months. Recently, the addition of bevacizumab, an angiogenesis inhibitor, has improved progression-free survival (PFS) when compared to paclitaxel/carboplatin alone. Sorafenib is an oral multi-kinase inhibitor with effects on tumor angiogenesis through inhibition of the VEGF receptor. The purpose of this randomized phase II study was to compare efficacy of paclitaxel/carboplatin with and without sorafenib. Methods: Women with histologically confirmed, maximally debulked, previously untreated stage III/IV epithelial ovarian carcinoma were randomized to receive paclitaxel 175 mg/m2and carboplatin AUC 6 (PC) or PC + sorafenib 400 mg PO BID (S). All patients received 6 cycles, given every 3 weeks; pts receiving PC+S continued single agent sorafenib for 52 weeks total. The primary endpoint was 2-year PFS rate. Results: 85 pts were randomized between 1/07 and 10/11 (PC+S 43; PC 42). Pt characteristics were similar between groups, except that more patients with only CA125 elevation received PC+S (65% vs 43%). Overall, 67 pts (79%) completed 6 cycles of chemotherapy (PC+S 74%; PC 83%). More patients stopped PC+S due to toxicity (14% vs 7%). 22 pts (51%) receiving PC+S began single agent S after 6 cycles PC, and 12 pts (28%) completed 52 weeks of S. There was no difference in the 2-year PFS rates: PC+S 40%, PC 39%. Overall survival comparisons were also similar (p = 0.36). Pts receiving PC+S had more grade 3 rash (33% vs 0%) and hand-foot syndrome (9% vs 0%). Conclusions: The addition of sorafenib did not improve the efficacy of standard first-line PC in pts with stage III/IV ovarian carcinoma, and resulted in additional toxicity. Clinical trial information: NCT00390611.

Synergistic Action of Benzyl Isothiocyanate and Sorafenib in a Nanoparticle Delivery System for Enhanced Triple-Negative Breast Cancer Treatment

“…Currently, SOR is utilized clinically for treating hepatocellular carcinoma, advanced renal cell carcinoma, and advanced thyroid carcinoma resistant to radioactive iodine, showing promising antitumor activities across various malignancies [6][7][8][9]. Its therapeutic application extends to numerous phase I, II, and III clinical trials, combined with other therapeutics such as with cisplatin plus docetaxel [10,11], paclitaxel [12][13][14], paclitaxel plus carboplatin [15,16] doxorubicin [17], oxaliplatin [18,19], gemcitabine [20,21], capecitabine [8,22], erlotinib [23], vemurafenib [24,25], and Tislelizumab [26].…”

Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review

“…Dose reductions were more common with sorafenib (67.5%) than placebo (30.1%), and duration of treatment was also shorter in the sorafenib arm (median 17.6 weeks vs. 51.9 weeks with placebo). Similarly, the addition of sorafenib to CP failed to improve 2-year PFS or OS rates in a randomized phase II trial as front-line treatment for stage III/IV ovarian cancer following cytoreductive surgery, but toxicity was increased with the combination regimen [ 66 ].…”