Dacarbazine (DTIC) plus bevacizumab (B) combination therapy in chemotherapy (CTh)-naïve advanced melanoma (MM) patients (pts): A phase II study.

Abstract

8536 Background: Advanced MM pts' poor prognosis is not improved by the neither of the 2 FDA approved agents, DTIC and IL-2 (median survival-time < 9 month [mo]; 5-yr survival-rate < 5%). Single-agent DTIC has average response-rate of 10% and median response-duration of 5-6 mo, being poly-CTh never proven to be superior. To improve such sober results, different DTIC- combinations have been proposed. MM in vitro models showed VEGF transcription up-regulation by DTIC, suggesting DTIC/anti-VEGF combination as an intriguing exploiting path. Methods: Between July 2006-September 2009, at IEO, Milan, 40 CTh-naïve advanced MM pts underwent CTh with DTIC (800 mg/mq q4w) + B (10 mg/kg q2w), being disease evaluated at each access by physical examination and every 3 cycles by whole-body (wb) CT-scan, according to RECIST criteria. Response rate, median TTP and safety were analyzed. Results: 36/40 pts were evaluated at the analysis-time, with 4 screening failures (3 pts: brain metastasis detection at the pre-study wb CT-scan; 1pts: bleeding risk). Male/Female = 23/13; median age was 57 yr. PS 0/1 = 32/4. 6 pts (16.6%) developed partial response (PR), 13 (36.1%) stable disease (SD ≥ 24w = 10 pts, 25.6%); 17 (47.2%) progressive disease (PD; 8 pts: RECIST-criteria PD at the first CT-scan evaluation; 9 pts: early clinical PD). PR pts were on average older (65.7 yrs; range 46.3-74.1) than both SD (57.2 yrs; range 33.1-78.5) and PD pts (51.4 yrs; range 31.6-76.3). Median TTP was 6 mo (95% CI 2.8-12.6). Furthermore, exploratory data analysis interestingly shows 42.2% clinical benefit (defined as PR+SD ≥ 24w) and 16.5 mo (95% CI 5-31.5) median survival. Treatment was well tolerated (mild hypertension and mucositis [8/36], easily controlled by symptomatics); 3 SAEs were recorded: 2 major cardiac events and 1 allergic reaction to B at the first administration. Conclusions: Long-lasting response obtained in both SD and PR pts and mild side effects support DTIC/B as a promising combination in advanced MM pts. We are currently investigating whether the molecular pattern and gene profiling of each patient can predict responders vs. nonresponders to the DTIC/B combination. No significant financial relationships to disclose.