Clinical responses to AZD6244 (ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma.

8501 Background: BRAF and NRAS mutations (mut) occur in 50-60% and 15-20% of melanomas, respectively. As a consequence, MAPK signaling is frequently activated. To correlate clinical benefit of a MEK inhibitor with the mut status, we performed a genomic study using tumors of patients (pts) enrolled in a clinical study of AZD6244 (a selective MEK inhibitor)-containing combination regimens. Methods: Pts ≥ 18 years of age with advanced solid tumors and a WHO performance status 0–1 were enrolled in a phase I trial of AZD6244 in combination with one of 3 drugs in 3-week (q3w) treatment cycles: dacarbazine (DTIC) 1000 mg/m2 iv q3w or docetaxel (Doc) 75 mg/m2 iv q3w or temsirolimus (Tems) 25 mg iv weekly. Oral AZD6244 was given at 50–75 mg twice daily continuously. Responses were assessed every 2 cycles per RECIST. In pts with available archived tumor samples, BRAF and NRAS were genotyped by pyrosequencing. Results: Among 25 pts with metastatic melanoma who received one of the combination regimens, tumor samples ...