FC10 Sorafenib and pegylated interferon alpha 2b in advanced metastatic melanoma: a multicenter phase II DeCOG trial

Background There is no standard of care for advanced metastatic melanoma (MM). Therefore the combination of a multi-kinase inhibitor such as sorafenib, and pegylated interferon alfa-2b (PegIFN), as previously used in renal cell cancer with some success, could potentially lead to an improved anti-tumoral response.

Methods Patients (pts) with previously untreated (excluding immunotherapy in the adjuvant setting), stage IV MM without brain metastasis, ECOG performance status 0–1 were eligible. All pts received PegIFN 3 μg/kg weekly once per week, and sorafenib 400 mg BID until progressive disease (PD). The primary endpoint was disease control rate (DCR) defined as CR+PR+SD after 8 weeks of treatment.

Results From February 2008 to February 2009, 55 pts were enrolled (ITT population). The median age was 64 years (range: 20–85); Pts were categorized as following: stage IV M1a/b/c=3/9/43. 41 pts (75%) received at least 8 weeks of treatment. Prior to 8 weeks evaluation, 9 pts withdrew due to toxicity, 2 revoked consent, and 3 had overt PD. At 8 weeks, 3 pts (5.5%) had a PR, 14 (25.5%) had a SD, resulting in a 31% DCR. Median PFS in these pts was 2.1 months (95% CI: 1.9–2.3). The toxicity of this combination was mainly haematological. Serious brain and GI bleeding complications occurred in 4 pts, where 2 had a fatal outcome. Other grade 3/4 toxicities were fatigue and flu-like symptoms.

Conclusion The combination of sorafenib and PegIFN showed modest clinical activity and some serious side effects including fatal bleeding complications. Due to these findings further testing of this combination is not warranted.