Westmead Institute for Cancer Research, Westmead Millennium Institute, Westmead Hospital, Sydney, Australia 7Discipline of Medicine, The University of Sydney, Sullivan, MD, Massachusetts General Hospital Cancer Center, 55 Fruit Street Yawkey 9E, Boston, MA 02114 Fax: (617) of Medicine, Division of Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 2Westmead Hospital, Sydney, Australia 3Department of Medicine, Division of Sleep Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 4Department of Medical Oncology, Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts 5Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, Massachusetts Small subsets of patients in larger studies or compassionate access programs.7 The patterns and rates of response areĬorresponding author: Ryan J. There is little evidence to guide sequencing decisions, other than comparisons across studies and ad hoc analyses of In patients with metastatic BRAF-mutant melanoma and more recently have received US regulatory approval in MayĢ013.4,5 Furthermore, the dabrafenib/trametinib combination has improved efficacy over single-agent dabrafenib.6 In theĬontext of this progress, a clinical dilemma has emerged regarding how best to sequence these agents in treating patients
A second BRAF inhibitor (BRAFi), dabrafenib, and the MEK inhibitor (MEKi) trametinib also improve response rates and survival compared with chemotherapy Randomized controlled trials.1-3 Consequently, both drugs have been approved for the treatment of unresectable stage IIIĪnd stage IV melanoma and have changed the standard of care for these patients. Mutant BRAF, have been shown to improve the overall survival (OS) of patients with metastatic melanoma in phase 3 Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen 4, and vemurafenib, a potent inhibitor of KEYWORDS: vemurafenib, sequencing, ipilimumab, melanoma, BRAF. Needed to define if sequencing IT prior to BRAFi therapy is superior to sequencing BRAFi prior to IT. Outcomes for IT with ipilimumab following BRAFi discontinuation are poor. CONCLUSIONS: In this retrospective analysis, prior treatment with IT does not appear to negatively influence respons e to BRAFi. Half could complete 4 doses of ipilimumab PFS with ipilimumab was 2.7 months (95% CI 5 1.8-3.1 months) and OS was 5.0 months Forty patients subsequently received IT with ipilimumab. Months (range of 1.8-4.4 months) from day of BRAFi discontinuation. A total of 193 patients discontinued BRAFi, with OS of 2.9 Results were similar when controlled for prognostic variables. RESULTS: RR and median PFS and OS calculated from commencement of BRAFi following IT 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.
METHODS: A cohort of patients treated with BRAFi alone or with MEK inhibitor was retrospectively This retrospective analysis describes the outcomes of patients treated with either BRAFiīefore IT or IT before BRAFi. Sullivan, MD5īACKGROUND: The immunotherapy (IT) agents ipilimumab and interleukin-2 as well as BRAF inhibitors (BRAFi) vemurafenib andĭabrafenib, with or without trametinib (MEK inhibitors), are all FDA-approved treatments for BRAF metastatic melanoma, but thereĪre few studies to guide optimal sequencing. Stephen Hodi, MD4 Richard Kefford, MBBS, PhD2,6,7,8 Alexander M. Lawrence, MD5 Anasuya Gunturi, MD1 Keith T. With Immunotherapy Prior to or After BRAF InhibitorsĪllison Ackerman, MD, PhD1 Oliver Klein, MD2 David F. Outcomes of Patients With Metastatic Melanoma Treated