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- March 28, 2014 at 1:24 pm
Immunotherapy in Melanoma Before or After BRAF Inhibitors
Research · February 27, 2014TAKE-HOME MESSAGE
- Treatment sequence of immunotherapy (IT) used before or after BRAF inhibitors for metastatic melanoma was evaluated. For IT (ipilimumab and IL-2) followed by BRAF inhibitors (n = 32), response rate was 57%, overall survival (OS) was 6.7 months, and progression-free survival was 19.6 months. These results were similar to when BRAF inhibitors were used initially. However, when IT was used after BRAF inhibitors were discontinued, the OS was only 2.9 months.
- “In this retrospective study, patients who received BRAF inhibitors after ipilimumab had a 57% response rate, in keeping with expected results. However, among a subset of patients receiving IT after progression on BRAF inhibitors, responses were poor. These data suggest that treatment with IT before BRAF inhibitors may be preferable in eligible patients.”
– Richard Bambury, MD
ABSTRACT
BACKGROUND
The immunotherapy (IT) agents ipilimumab and interleukin-2 as well as BRAF inhibitors (BRAFi) vemurafenib and dabrafenib, with or without trametinib (MEK inhibitors), are all FDA-approved treatments for BRAF metastatic melanoma, but there are few studies to guide optimal sequencing. This retrospective analysis describes the outcomes of patients treated with either BRAFi before IT or IT before BRAFi.
METHODS
A cohort of patients treated with BRAFi alone or with MEK inhibitor was retrospectively identified. Response rate (RR), overall survival (OS), and progression-free survival (PFS) were evaluated for the entire cohort, subdivided by BRAFi prior to or after IT.
RESULTS
RR and median PFS and OS calculated from commencement of BRAFi following IT (N = 32) were 57%, 6.7 months (95% confidence interval [CI] = 4.3-9.1 months), and 19.6 months (95% CI = 10.0-undefined months), respectively; whereas for BRAFi initially (N = 242) were 66%, 5.6 months (95% CI = 4.7-6.8 months), and 13.4 months (95% CI = 10.1-17.0 months). Results were similar when controlled for prognostic variables. A total of 193 patients discontinued BRAFi, with OS of 2.9 months (range of 1.8-4.4 months) from day of BRAFi discontinuation. Forty patients subsequently received IT with ipilimumab. Only half could complete 4 doses of ipilimumab; PFS with ipilimumab was 2.7 months (95% CI = 1.8-3.1 months) and OS was 5.0 months (95% CI = 3.0-8.8 months).
CONCLUSIONS
In this retrospective analysis, prior treatment with IT does not appear to negatively influence response to BRAFi. Outcomes for IT with ipilimumab following BRAFi discontinuation are poor. Randomized controlled trials are needed to define if sequencing IT prior to BRAFi therapy is superior to sequencing BRAFi prior to IT.
CancerOutcomes of Patients With Metastatic Melanoma Treated With Immunotherapy Prior to or After BRAF Inhibitors
Cancer 2014 Feb 27;[EPub Ahead of Print], A Ackerman, O Klein, DF McDermott, W Wang, N Ibrahim, DP Lawrence, A Gunturi, KT Flaherty, FS Hodi, R Kefford, AM Menzies, MB Atkins, GV Long, RJ Sullivan
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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