Abstract
ABSTRACT Aim: The treatment of advanced melanoma has dramatically changed with the use of novel targeted and immunotherapeutic agents. Many patients survive longer and the question of treatment and prognosis beyond BRAF inhibitor (BRAFi) is still unanswered. Methods: We retrospectively analysed data from patients treated in our centre from June 2011 to April 2014. Patients with BRAF mut MM treated with BRAFi in any line were included. Results: A total of 32 BRAF-mut MM patients were analysed; most (29) had received at least one previous line of systemic treatment. Ten patients received no further treatment at BRAFi progression due to rapid disease deterioration. From 22 patients treated beyond BRAFi, 12 (54%) received chemotherapy, 5 (23%) Ipilimumab and 5 (23%) re-challenge with a different BRAFi or BRAF/MEKi combination. As of April 2014, median overall survival (OS) of all patients from BRAF initiation was 7.0 months (range 3-33 months). Median OS after BRAFi was 2 months (range 1-33) for all BRAFi- treated patients, while for the 22 patients treated beyond progression OS after BRAFi was 5 months (range 1.5–33). Most patients treated with Ipilimumab beyond BRAFi (4/5) had clinical benefit, with one long lasting CR for 2 years. These were all patients with slow progression after long lasting responses to BRAFi. Median OS beyond BRAFi for those receiving Ipilimumab was 6 months (range 2-28.5). Patients receiving chemotherapy beyond BRAFi had less benefit with few responses (3/12 PR) and OS 2.75 months (range 1.5-13.5). Finally, from the 5 patients re-challenged beyond BRAFi, 2 are still alive on BRAF/MEKi combination and 1 patient receiving a different BRAFi due to toxicity is alive progression-free for 33 months. Median OS beyond BRAFi for those patients was 7 months (range 2-33). Conclusions: The prognosis of MM patients after progression on BRAFi is poor. However, subsets of patients treated beyond BRAFi live longer. In our cohort, patients treated with either Ipilimumab or re-challenged with another BRAFi or BRAF/MEKi combination had significant OS benefit. Although numbers are small, our data on poor prognosis BRAFi-treated MM patients are encouraging, showing that treatment beyond BRAFi progression should be further explored. Disclosure: All authors have declared no conflicts of interest.
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