Treatment patterns of melanoma by BRAF mutation status in the USA from 2011 to 2017: a retrospective cohort study
MELANOMA MANAGEMENT
Authors: Shah, Shweta; Raskin, Leon; Cohan, David; Hamid, Omid; Freeman, Morganna L.
Abstract
Aim: To describe treatment changes from 2011 to 2017 and demographic/clinical characteristics of patients with advanced melanoma who received systemic therapy by BRAF status. Patients & methods: Treatment patterns were evaluated in adults from the Oncology Services Comprehensive Electronic Records database who received antimelanoma systemic therapy. Results: Checkpoint inhibitors were prevailingly prescribed (66%); usage increased from 2011 (21%) to 2017 (84%). BRAF/MEK inhibitors were the second most common (21%); usage increased from 2011 (6%) to 2012 (18%) and stabilized until 2017 (22%). BRAF/MEK inhibitors (65%) and checkpoint inhibitors (57%) were predominantly used for BRAF(Mut) melanoma. Conclusion: Overall, checkpoint inhibitors have supplanted other therapies for advanced melanoma. Treatment shifts have occurred for BRAF(Mut) melanoma, notably increased use of checkpoint inhibitors and BRAF/MEK combinations compared with monotherapies.
Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial
BLOOD ADVANCES
Authors: Voso, Maria Teresa; Larson, Richard A.; Jones, Dan; Marcucci, Guido; Prior, Thomas; Krauter, Jurgen; Heuser, Michael; Lavorgna, Serena; Nomdedeu, Josep; Geyer, Susan M.; Walker, Alison; Wei, Andrew H.; Sierra, Jorge; Sanz, Miguel A.; Brandwein, Joseph M.; de Witte, Theo M.; Jansen, Joop H.; Niederwieser, Dietger; Appelbaum, Frederick R.; Medeiros, Bruno C.; Tallman, Martin S.; Schlenk, Richard F.; Ganser, Arnold; Amadori, Sergio; Cheng, Yuan; Chen, YinMiao; Pallaud, Celine; Du, Ling; Piciocchi, Alfonso; Ehninger, Gerhard; Byrd, John; Thiede, Christian; Dohner, Konstanze; Stone, Richard M.; Dohner, Hartmut; Bloomfield, Clara D.; Lo-Coco, Francesco
Abstract
The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations. At a median follow-up of 60.7 months (95% CI, 55.0-70.8), the 5-year event-free survival (EFS) rate was significantly higher in patients treated with midostaurin than in those treated with placebo (45.2% vs 30.1%; P=.044). A trend toward improved disease-free survival was also observed with midostaurin (67.3% vs 53.4%; P=.089), whereas overall survival (OS) was similar in the 2 groups. Patients with AML and NPM1(mut)/FLT3-TKDmut or core binding factor (CBF)-rearranged/FLT3-TKDmut genotypes had significantly prolonged OS with or without censoring at hematopoietic cell transplantation (HCT), compared with NPM1(WT)/CBF-negative AMLs. The multivariable model for OS and EFS adjusted for allogeneic HCT in first complete remission as a time-dependent covariable, revealed NPM1 mutations and CBF rearrangements as significant favorable factors. These data show that NPM1 mutations or CBF rearrangements identify favorable prognostic groups in patients with FLT3-TKD AMLs, independent of other factors, also in the context of midostaurin treatment.