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 session3713 - ZUMA-3: A phase 1/2 multi-center study evaluation the safety and efficacy of KTE-C19 anti-CD19 CAR T cells in adult patients with relapsed/refractory B precursor acute lymphoblastic leukemia (R/R ALL)Presenter: Bijal Shah Session: Poster display Resources: Abstract 3305 - ZUMA-2: A phase 2 multi-center study evaluating the efficacy of KTE-C19 (Anti-CD19 CAR T cells) in patients with relapsed/refractory Mantle cell lymphoma (R/R MCL)Presenter: Michael Wang Session: Poster Display Resources: Abstract 3222 - ZUMA-1: A phase 2 multi-center study evaluating anti-CD19 chimeric antigen receptor (CAR) T cells in patients with refractory aggressive non-Hodgkin lymphoma (NHL)Presenter: Sattva Neelapu Session: Poster Display Resources: Abstract 1560 - Younger age as a prognostic indicator in breast cancer: Correlation between clinical-pathologic factors and miRNAs and long-term follow-upPresenter: Maria Teresa Martinez Session: Poster display Resources: Abstract 2335 - Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)Presenter: Christy Toms Session: Poster display Resources: Abstract 3291 - Whole exome sequencing (WES) and RNA sequencing (RNA-seq) in routine clinical practice for colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) patients (pts)Presenter: Géraldine Perkins Session: Poster display Resources: Abstract 3607 - What is the optimal annual interpretive volume for a radiologist reading screening mammograms?Presenter: Asli Uluturk Session: Poster display Resources: Abstract 1963 - What decides breast conservation versus mastectomy in the background of diverse sociocultural environment, an Indian studyPresenter: Poonamalle Padmanabhan Bapsy Session: Poster display Resources: Abstract 3503 - Waiting time to diagnosis and treatment of the head and neck cancer in four institutions in PortugalPresenter: Ana Castro Session: Poster display Resources: Abstract 1997 - Wait times for diagnosis and treatment of lung cancer: a single centre experiencePresenter: Catherine Labbe 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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