Abstract A3: Axitinib combined with paclitaxel and carboplatin in melanoma: Response in genetically selected subsets

Background: Axitinib is a potent VEGFR inhibitor. We tested the hypothesis that axitinib could increase the effectiveness of carboplatin/paclitaxel in specific subtypes of advanced melanoma. Methods: A prospective single arm phase I/II trial of this combination was initiated August 2010 in metastatic melanoma (NCT01174238) at UCSF. Twenty seven patients have been enrolled, 16 are evaluable for response to date. Patients had an ECOG PS 0–1, and normal organ function. Axitinib 5 mg PO bid was taken days 1 − 14 of each 21-day cycle, and carboplatin/paclitaxel was administered on day 21. Biopsy specimens were sequenced for mutations in BRAF, NRAS, c-KIT, GNAQ and G11 and FLT-PET scans were done in selected patients to on days 1, 14, 17, and 20 of cycle 1. Results: This regimen was well tolerated with adverse events including GI toxicity, musculoskeletal pain, fatigue, hypertension, and mild sensory neuropathy. Grade 3 adverse events have been uncommon, and grade 4 adverse events have not been observed. Four of 13 WT/NRAS patients have had a PR by RECIST, 7/13 have had some shrinkage of tumor while only 2/13 have had PD. Of the 3 patients with BRAF V600 E/K mutations, all have had PD. In the overall study population, median OS and PFS have not been reached. Conclusions: Striking activity was seen in patients whose tumors are WT for BRAF including those with NRAS mutation. Given the urgent need for effective therapies in this population, this combination warrants further study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A3.