LBA51 - Phase 2 Trial (BRF113928) of Dabrafenib (D) Plus Trametinib (T) in Patients (pts) With Previously Untreated BRAF V600E–Mutant Metastatic Non-Small...

Date 11 September 2017
Event ESMO 2017 Congress
Session NSCLC, metastatic 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Lung and other Thoracic Tumours
Personalised Medicine
Presenter David Planchard
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors D. Planchard1, E.F. Smit2, H.J.M. Groen3, J. Mazieres4, B. Besse5, Å. Helland6, V. Giannone7, A. D'Amelio7, P. Zhang7, B. Mookerjee7, B. Johnson8
  • 1Department Of Medical Oncology, Gustave Roussy, 94805 - Villejuif/FR
  • 2Thoracic Oncology, Vrije Universiteit VU Medical Centre, Amsterdam/NL
  • 3Department Of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen/NL
  • 4Thoracic Oncology Department, Rangueil-Larrey Hospital, Paul Sabatier University, Toulouse/FR
  • 5Department Of Medicine, Gustave Roussy, Villejuif/FR
  • 6Cancer Genetics, Oslo University Hospital, Oslo/NO
  • 7Medical Oncology, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 8Department Of Medical Oncology, Dana-Farber Cancer Institute, Boston/US

Abstract

Background

BRAF V600E mutation occurs in ≈ 1%-2% of lung adenocarcinomas. D+T showed substantial clinical activity in pts with previously treated BRAF V600E–mutant metastatic NSCLC, with an investigator (INV)-assessed confirmed overall response rate (ORR) of 67%, median progression-free survival (PFS) of 10.2 mo, and median overall survival (OS) of 18.2 mo. We report results of D+T therapy in treatment-naive pts with BRAF V600E–mutant metastatic NSCLC.

Methods

In this cohort of the phase 2 BRF113928 trial (NCT01336634), pts with BRAF V600E–mutant metastatic NSCLC without prior systemic therapy for metastatic disease received D 150 mg twice daily + T 2 mg once daily. The primary endpoint was INV-assessed ORR. Secondary endpoints included duration of response (DOR), PFS, OS, and safety.

Results

36 pts received D+T as first-line therapy. At the data cutoff (28 Apr 2017), median follow-up was 15.9 mo, and 11 pts (31%) remained on study treatment. Median age was 67 y (range, 44-91 y); most pts were female (61%), white (83%), and current/former smokers (72%). The INV-assessed confirmed ORR was 64% (95% CI, 46%-79%), with 2 complete responses (6%) and 21 partial responses (58%). Four pts (11%) had stable disease ≥ 12 wk (disease control rate, 75% [95% CI, 58%-88%]). These results were supported by independent review committee assessment. INV-assessed median DOR was 10.4 mo (95% CI, 8.3-17.9 mo), and median PFS was 10.9 mo (95% CI, 7.0-16.6 mo; 24 pts progressed or died). Median OS was 24.6 mo (95% CI, 12.3 mo-not estimable; 17 pts died). All pts experienced ≥ 1 adverse event (AE), and 69% had ≥ 1 grade 3/4 AE. Serious AEs (SAEs) in > 2 pts included alanine aminotransferase increase (14%), pyrexia (11%), aspartate aminotransferase increase (8%), and ejection fraction decrease (8%). One pt died due to an SAE (cardiorespiratory arrest) that was determined to be unrelated to study treatment.

Conclusions

D+T demonstrated clinically meaningful antitumor activity and a manageable safety profile in pts with previously untreated BRAF V600E–mutant metastatic NSCLC, supporting recent approval by the European Commission and US FDA.

Clinical trial identification

Clinical trial ID: NIH ClinicalTrials.gov NCT01336634 First received April 7, 2011

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation

Funding

Novartis Pharmaceuticals Corporation

Disclosure

D. Planchard: Consultancy/Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Pfizer, Roche, Novartis, Chugai. E.F. Smit: Consulting/Advisory Role: Lillly Research Funding: Boehringer Ingelheiim, Bayer, Roche/Genentech, AstraZeneca. H.J.M. Groen: Consulting/Advisory Role: Pfizer, Novartis, Bristol-Meyers Squibb, MSD Oncology, Lilly, Abbvie, Roche/Genentech Research Funding: Lilly, Roche. J. Mazieres: Research Funding: Roche, Bristol-Myers Squibb. B. Besse: Research Funding: AstraZeneca, Roche/Genentech, Pfizer, Boehringer Ingelheim, Lilly, Servier, Onxeo, Bristol-Myers Squibb, Ose Pharma, Inivata, Novartis Travel/Accommodations/Expenses: Roche, Pfizer, Bristol Myers Squibb/Medarex, Novartis, Pierre Fabre. V. Giannone, P. Zhang: Employment: Novartis. A. D\'Amelio: Employment: Novartis Stock or Other Ownership: Novartis, GlaxoSmithKline. B. Mookerjee: Employment: Novartis, GlaxoSmithKline Stock or Other Ownership: Novartis, GlaxoSmithKline, Incyte, AstraZeneca. B. Johnson: Stock or Other Ownership: KEW Group Honoraria: Chugai Consulting/Advisory Role: Novartis, Eli Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Clovis, Genentech, Merck Grant: Toshiba Post Marketing Royalties (DFCI): EGFR Mutation Testing. All other authors have declared no conflicts of interest.