Nab-paclitaxel and bevacizumab as first-line therapy in patients with unresectable stage III and IV melanoma

Abstract

9061^ Background: Nab-paclitaxel (Abraxane) increases intra-tumoral concentrations of paclitaxel and has efficacy superior to that of paclitaxel for the treatment of metastatic breast cancer (J Clin Oncol 2005:23:7794–7803). Nab-paclitaxel demonstrated single agent activity in metastatic melanoma. (ASCO 2005:7558) Bevacizumab is a monoclonal antibody that targets VEGF resulting in inhibition of tumor angiogenesis and enhances tumor response to paclitaxel. (NEJM 2007:357:2666–2676) Methods: Eligible were chemotherapy-naïve patients with unresectable stage III or IV melanoma, ECOG performance status of 0–1, and adequate organ function. The treatment regimen was given in a 28-day cycle in which nab-paclitaxel 150 mg/m2 was administered on days 1, 8, and 15 and bevacizumab 10mg/kg on days 1 and 15 until disease progression or dose limiting toxicity. Response assessments were made by RECIST criteria every 2 cycles. Results: Forty-one patients have been treated since 08/15/07. Over 50% of the patients had stage IV, MIc disease. The median duration of follow-up for progression-free survival from start of protocol treatment is 5.3 months. Progression-free survival at 4 months is 83%,(95%CI:69%-97%). Median progression free survival is 6.25 months (95%CI: 5.63–9.41). The median duration of follow-up for survival is 4.7 months. Three patients have died and 38 patients remain alive. The 6 month survival rate is 91% (95%CI:79%-100%).The 12 month survival rate is 83% (95% CI:65%-100%). The median duration of overall survival has not been reached yet. Dose modifying toxicities consisted primarily of neutropenia, neuropathy, and hypertension. Conclusions: Early experience suggests that nab-paclitaxel and bevacizumab is an effective and well-tolerated regimen as first-line therapy in patients with metastatic melanoma. The study is ongoing with an accrual target of 50 patients. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .