Durable response of the triple combination of temozolomide, sorafenib, and bevacizumab to treat refractory stage IV acral melanoma.

8564 Background: Metastatic acral melanoma is a rapid progressing and refractory disease which accounts for 50% in China. VEGF, MAPK and NF-KB, which are targets of bevacizumab, sorafenib and temozolomide (TMZ) respectively, are vertical joint which inhibits melanoma cells from membrane, cytoplasm to nuclei. We conducted a phase II trial of the triple combination to test synergistic effects on metastatic acral melanoma. Methods: Patients (Pts) with stage IV (M1c) unresectable acral melanoma, who have failed at least one systemic regimen, are eligible. The pts were treated with TMZ 200 mg/m2/d (days 1- 5), bevacizumab 5 mg/Kg (days 1, 14) and sorafenib 400 mg/bid (days 1-28), repeatedly every 28 days. KIT, VEGFR and PDGFR protein of tumor tissue were detected and genetic aberrations including KIT and BRAF were analyzed by Immunohistrochemistry (IHC) assay and DNA sequencing respectively. The endpoints were progression-free survival (PFS), overall survival (OS), response and toxicity. Correlation was decided between gene mutations, IHC results and clinical response. Results: 50 patients were planned to recruit. 35 pts were currently enrolled and evaluated. One patient has achieved complete response (CR) lasting 16+months. Eight pts have achieved partial response (PR) (duration range: 4.4∼7.2+ months). 15 pts received SD (> 3 m) with duration from 3.2 to 12+months. The response rate was 25.7% (9/35). PFS has not reached (at least 3.8 months). It's too early to assess overall survival. 30 pts had IHC and aberration results. The positive rates of KIT protein were 35% (PR+SD) pts and 42% in PD pts, of VEGFR were 26% s and 57%; of PDGFR were 84% and 57% respectively (p > 0.05). Five patients were found harboring BRAF V600E mutations (1CR, 4PD) and one of them had KIT amplification simultaneously (response: PD). The common toxicity was moderate including hand-foot syndrome (G3/4:11.4%), myelosuppression (G3/4:11.4%), diarrhea (G3/4:2.8%), fatigue and hoarse. Conclusions: The triple combination regimen preliminary achieved durable clinical response. The regimen is safe and well tolerated. It seemed no correlation between positive IHC results, gene mutations and responses. No significant financial relationships to disclose.