Abstract 2016
Background
Phase 2 (BRF113220 [NCT01072175]) and phase 3 (COMBI-d [NCT01584648], COMBI-v [NCT01597908]) trials provide a large dataset for evaluating D + T in patients (pts) with BRAF V600E/K–mutant melanoma. Pooled analyses showed that D + T efficacy across studies (N = 617) is consistent with that in individual trials (response, 67%; median progression-free survival [PFS], 11.1 mo [95% CI, 9.7-12.9]; median overall survival [OS], 25.6 mo [95% CI, 23.1-34.3]) and identified factors associated with these outcomes. Here we describe additional analyses to determine factors that predict durable outcomes (≥ 24 mo) in the pooled D + T population.
Methods
The pooled population included randomized pts treated with D 150 mg twice daily + T 2 mg once daily in BRF113220 (Part C; cutoff Jan 2015), COMBI-d (cutoff Jan 2015), and COMBI-v (cutoff Mar 2015). Baseline factors (Table) were analyzed by regression tree analyses to identify predictors of D + T treatment (Tx), PFS, or OS lasting ≥ 24 mo.
Results
Of 617 pts treated with D + T in BRF113220 (n = 54), COMBI-d (n = 211), and COMBI-v (n = 352), 165 (27%) received it for ≥ 24 mo. Long-term PFS (n = 472) and OS (n = 456) analyses excluded pts censored prior to 24 mo. A total of 85 pts (18%) had PFS ≥ 24 mo and 186 (41%) had OS ≥ 24 mo (Table). Regression tree analyses identified baseline lactate dehydrogenase (LDH) as the most predictive factor for durable benefit. Pts with normal vs elevated LDH had improved PFS (median: 12.1 vs 5.5 mo; 2-y rate: 26% vs 5%) and OS (median: 31.6 vs 10.8 mo; 2-y rate: 56% vs 15%). At data cutoff, 172 pts (28%) remained on D + T, including 140 (81%) with Tx ≥ 24 mo and 69 (40%) with PFS ≥ 24 mo.
| Characteristic | PFS ConclusionsLong-term Tx and durable PFS and OS were achieved in a subset of pts with BRAF V600–mutant melanoma receiving D + T. Baseline LDH was the strongest predictor for PFS and OS ≥ 24 months. Additional follow-up/analyses are needed to further define the durability of PFS and OS achievable with D + T. Clinical trial identificationNCT01597908; first received by CT.gov on May 10, 2012 and NCT01584648; first received by CT.gov on April 23, 2012 and NCT01072175; first received by CT.gov on February 12, 2010 Legal entity responsible for the studySupported by GlaxoSmithKline. Dabrafenib and trametinib are assets of Novartis AG as of 2 March 2015. FundingSupported by GlaxoSmithKline. Dabrafenib and trametinib are assets of Novartis AG as of 2 March 2015. DisclosureM. Davies: Research funding: Genentech/Roche, GlaxoSmithKline, AstraZeneca, Sanofi-Aventis, Merck Membership on board of directors or advisory committees: Novartis, Genentech/Roche, GlaxoSmithKline, Sanofi-Aventis, Vaccinex. J.J. Grob: Consultancy: Novartis, GlaxoSmithKline, Roche, Merck, Bristol-Myers Squibb, Amgen. G.V. Long: Consultancy: Roche, Bristol-Myers Squibb, Merck, Amgen, Novartis Honoraria: Bristol-Myers Squibb, Merck, Novartis. K. Flaherty: Consultancy: Novartis, Roche, Array, Lilly, Takeda Research funding: Novartis. P. Nathan: Consultancy: Novartis Speakers Bureau: Novartis Membership on board of directors or advisory committees: Novartis. A. Ribas: Consultancy: Novartis, Merck, Pfizer, Roche Equity Ownership: Kite Pharma Honoraria: Novartis. D. Schadendorf: Consultancy, Honoraria, Speakers Bureau: Amgen, Novartis, Roche, BMS, MSD/Merck, Pfizer Research Funding: BMS, MSD/Merck Membership on board of directors: Amgen, Novartis, Roche, BMS, MSD/Merck, Pfizer, Array. B. Mookerjee: Employment: Novartis Equity Ownership: Novartis, GlaxoSmithKline, Incyte, AstraZeneca. J.J. Legos: Employment: Novartis Own company stock: Novartis. S. Lane: Employment: Novartis. C. Robert: Consultancy: Novartis, Amgen, BMS, Merck, Roche Honoraria: Novartis, Amgen, BMS, Merck, Roche. Resources from the same session2354 - The clinicopathologic features and treatment of 607 hindgut neuroendocrine tumor (NET) patients at a single institutionPresenter: Seung Tae Kim Session: Poster Display Resources: Abstract 2594 - Neuroendocrine carcinomas of the colorectal origin - Polish experiencePresenter: Agnieszka Kolasińska-Ćwikła Session: Poster Display Resources: Abstract 2539 - Neuroendocrine neoplasms of the appendix including goblet cell carcinoidsPresenter: Agnieszka Kolasinska-Cwikla Session: Poster Display Resources: Abstract 1245 - Prognostic validity of AJCC staging system in neuroendocrine tumors of the appendixPresenter: Amir Mehrvarz Sarshekeh Session: Poster Display Resources: Abstract 3902 - Enhancer of zest homolog 2 (EZH2) expression in well and moderately differentiated pancreatic neuroendocrine tumor (pNET)Presenter: Riccardo Marconcini Session: Poster Display Resources: Abstract 3882 - Differential clinical and pathological characteristics of hereditary neuroendocrine pancreatic tumours (NEPT)Presenter: Gema Marín Zafra Session: Poster Display Resources: Abstract 2296 - Natural course of thyroid cancer nodules compared with benign thyroid nodulesPresenter: Kyung-Jin Yun Session: Poster Display Resources: Abstract 4083 - Reassessment of proliferative activity at disease progression in neuroendocrine neoplasmsPresenter: Noemi Cicchese Session: Poster Display Resources: Abstract 3866 - 18F-FDG-PET to predict disease progression in advanced digestive neuroendocrine neoplasmsPresenter: Maria Rinzivillo Session: Poster Display Resources: Abstract 3651 - UK phase IV, observational study to assess quality of life in patients (pts) with pancreatic neuroendocrine tumours (pNETS) receiving treatment with everolimus: The “real-world” OBLIQUE studyPresenter: John Ramage Session: Poster Display Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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