101P - Association between time to progression and subsequent survival in previously treated BRAF V600E-mutant metastatic non-small cell lung cancer

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Thoracic Malignancies
Non-Small Cell Lung Cancer
Presenter Medha Sasane
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors M. Sasane1, J. Li2, J. Zhang3, J. Zhao2, M.L. Ricculli4, S. Redhu3, J. Signorovitch2
  • 1Novartis, 07936 - East Hanover/US
  • 2Analysis Group Inc., Boston/US
  • 3Novartis, East Hanover/US
  • 4Analysis Group Inc., New York/US

Abstract

Background

Time to progression (TTP) has been associated with prolonged post-progression survival (PPS) in ALK positive non-small cell lung cancer (NSCLC). However, such associations have not yet been assessed among previously treated metastatic NSCLC patients with BRAF V600 mutation who received BRAF-specific targeted therapies. This study evaluated the TTP-PPS association among previously treated BRAF V600E-mutant metastatic NSCLC patients receiving the BRAF inhibitor dabrafenib as a single agent or in combination with the MEK inhibitor trametinib.

Methods

Patients who experienced disease progression in an open-label, non-randomized, Phase II study (NCT01336634) of 2nd-line or later treatment with dabrafenib monotherapy or combination therapy with trametinib were included. Progression was defined per RECIST v1.1. Time from progression to death (PPS) was studied in a Kaplan-Meier analysis with patients stratified by shorter (< 6 months) versus longer TTP (≥ 6 months). The association between TTP and PPS was also quantified in Cox proportional hazards models.

Results

A total of 84 patients who progressed on dabrafenib monotherapy or combination therapy were included in this study, with 77% having ECOG performance score > 0 at screening. Prior to progression, 57 received dabrafenib monotherapy and 27 received combination therapy with trametinib. Among all patients included, 60 (71%) died during post-progression follow-up. Patients with TTP ≥ 6 months experienced significantly longer PPS compared to those with TTP < 6 months (median PPS: 9.5 vs. 2.7 months, log-rank p-value < 0.001). In the proportional hazards model for the full cohort, each 3 months of longer TTP was associated with a 32% lower hazard of death following progression (hazard ratio [95% confidence interval]: 0.68 [0.57, 0.83]). A similar positive association between TTP and PPS was observed in each treatment group (monotherapy: 0.70 [0.57, 0.88]; combination therapy: 0.57 [0.34, 0.97]).

Conclusions

A longer duration of TTP after treatment with dabrafenib monotherapy or combination therapy was significantly associated with a longer duration of PPS.

Clinical trial identification

NCT01336634

Legal entity responsible for the study

Novartis

Funding

Financial support for the study were provided by Novartis.

Disclosure

M. Sasane: Employee of Novartis and own Novartis stock or stock options. J. Li: Employed by Analysis Group, Inc., payment from Novartis for participation in this research. J. Zhang: Employee of Novartis and own Novartis stock or stock options. J. Zhao: Employed by Analysis Group, Inc., payment from Novartis for participation in this research. M.L. Ricculli: Employed by Analysis Group, Inc., payment from Novartis for participation in this research. S. Redhu: Employee of Novartis and own Novartis stock or stock options. J. Signorovitch: Employed by Analysis Group, Inc., payment from Novartis for participation in this research.