Clinical outcome of patients with metastasic melanoma undergoing phase I clinical trials.

Abstract

8564 Background: Dacarbazine (DTIC) and interferon (IFN) are two agents currently used in the treatment of malignant melanoma (MM). They have modest response rates (RR) and marginal improvement in time to progression (TTP) or survival. The recently published results of targeted agents such as ipilimumab and PLX4032 are encouraging, and will one day replace these agents as front line treatment. We hypothesize that clinical outcomes of patients (pts) with MM treated with targeted therapies on phase I clinical trials are equivalent to those seen with agents such as DTIC or IFN. Methods: We analyzed the outcomes of 65 patients with MM that had undergone treatment in our phase I clinical trials unit between 2005-2010. All pts had received at least one previous line of systemic treatment and acted as theis own controls. RR and TTP on previous treatment was compared to RR and TTP on the phase I trial. Differences were studied by a Chi-squared test and the log-rank test respectively. A Cox analysis was performed to identify clinical variables that could influence TTP. Results: 27 females and 38 males were included. Mean age was 56 years. Performance status (PS) was 0 in 26 pts,1 in 35 pts and 2 in 4 cases. First line of treatment included DTIC or temozolamide in 58 pts, IFN in 5 pts and cisplatin based treatment in 2 pts. 25 pts had received previous treatment on a Phase II/III trial and data regarding best response to previous treatment was not available in 3 pts. There was no statistical significant difference in RR between to the first line treatment with chemotherapy or cytokine therapy vs treatment with a targeted agent in phase I trial (7/65) 11% vs (9/65) 14%, p=0.87. In addition there was no difference in TTP on the first line treatment vs treatment with a targeted agent in phase I trial; 90 days (95% CI 65-120) vs 53 days (95% CI 42-79), p= 0.15. No clinical variable showed influence on TTP. Conclusions: This data emphasize the lack of superiority of DTIC and IFN based regimes over targeted experimental agents for the treatment of MM. In event of progression to treatment with targeted agents as ipilimumab or PLX4032, patients should be considered for clinical trials with investigational agents rather than receiving chemotherapy or cytokine therapy.