8519 Background: Vemurafenib (V; RG7204, PLX4032), a BRAF inhibitor, induces responses in a majority of patients (pts) with V600EBRAF mutant melanoma, but most eventually progress. We report the patterns of disease progression (PD) of pts with MM treated on the phase I study of V.
METHODS
Dose escalation cohort pts were treated with V 240-1,120 mg po BID, and MTD extension cohort pts with 960 mg BID. Clinical response was evaluated by RECIST every 8 weeks. Pts with PD in a disease site for which local therapy (surgery or radiotherapy) was feasible were allowed to continue on V post-progression. Survival from time of progression was estimated for pts who were and were not treated post-progression.
RESULTS
48 pts (16 escalation, 32 extension cohort) with V600EBRAF mutation were treated. Median age 53 yrs, 27 (56%) male, 35 (73%) M1c, 27 (56%) ECOG PS of 1, and 23 (48%) had received ≥ 2 prior systemic therapies. Median OS has not been reached for all 48 pts (median follow up [F/U] was 12.5 mo (range 1.2-29.2). The common sites of PD were: Skin/soft tissue (44% of all 48 pts); nodes (27%); brain/CNS (25%); lungs (19%); liver (15%); bone, GI (10%). Among 42 pts with PD, 19 (45%) progressed only in new sites, 8 (19%) in the brain only and 11 (26%) in both new and original sites. Among 18 pts who continued PLX4032 >30 days after a local therapy of a PD lesion(s), a median OS has not been reached with a median F/U of 15.5 mo from initiation of PLX4032. Median treatment duration beyond initial PD was 3.6 mo (range, 1.1-9.9), and median OS from the time of initial PD has not been reached (median F/U 6.0 mo). For pts who did not continue treatment after PD, median OS from the time of PD was 1.4 mo. Adverse events during continued dosing in these pts were similar to those observed before PD.
CONCLUSIONS
For subset of pts with PD in limited sites, continuation of PLX4032 treatment beyond PD is potentially beneficial after a local therapy. Further study of the impact of post-progression treatment is warranted while mechanisms of resistance and novel agents for MM are emerging. [Table: see text].