Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis

doi:10.1016/j.jtho.2021.08.011

Journal of Thoracic Oncology

Volume 17, Issue 1, January 2022, Pages 103-115

https://doi.org/10.1016/j.jtho.2021.08.011 Get rights and content

Under a Creative Commons license

open access

Abstract

Introduction

Dabrafenib plus trametinib was found to have robust antitumor activity in patients with BRAF V600E-mutant metastatic NSCLC (mNSCLC). We report updated survival analysis of a phase 2 study (NCT01336634) with a minimum of 5-year follow-up and updated genomic data.

Methods

Pretreated (cohort B) and treatment-naive (cohort C) patients with BRAF V600E-mutant mNSCLC received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points were duration of response, progression-free survival, overall survival, and safety.

Results

At data cutoff, for cohorts B (57 patients) and C (36 patients), the median follow-up was 16.6 (range: 0.5–78.5) and 16.3 (range: 0.4–80) months, overall response rate (95% confidence interval [CI]) was 68.4% (54.8–80.1) and 63.9% (46.2–79.2), median progression-free survival (95% CI) was 10.2 (6.9–16.7) and 10.8 (7.0–14.5) months, and median overall survival (95% CI) was 18.2 (14.3–28.6) and 17.3 (12.3–40.2) months, respectively. The 4- and 5-year survival rates were 26% and 19% in pretreated patients and 34% and 22% in treatment-naive patients, respectively. A total of 17 patients (18%) were still alive. The most frequent adverse event was pyrexia (56%). Exploratory genomic analysis indicated that the presence of coexisting genomic alterations might influence clinical outcomes in these patients; however, these results require further investigation.

Conclusions

Dabrafenib plus trametinib therapy was found to have substantial and durable clinical benefit, with a manageable safety profile, in patients with BRAF V600E-mutant mNSCLC, regardless of previous treatment.

Keywords

BRAF V600E

Dabrafenib

Genomic analysis

Non–small cell lung cancer

Trametinib

Cited by (0)

: Disclosure: Planchard acts as a principal investigator/coinvestigator at AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo; and acts as advisory and reports receiving personal fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Celgene, Daiichi Sankyo, Merck, Novartis, Pfizer, priME Oncology, Peer CME, Roche, and Samsung. Besse reports receiving grants from Inivata, Janssen, Merck KGaA, Merck Sharp & Dohme, Nektar, Onxeo, OSE Immunotherapeutics, Pfizer, PharmaMar, Roche-Genentech, Sanofi, Serier, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma, and Tolero Pharmaceuticals. Groen acts as an advisor for Eli Lilly and investigator for Novartis and Boehringer Ingelheim. Mazieres reports receiving grants from Roche, AstraZeneca, and Pierre Fabre; and acts as advisor for Merck, Roche, AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, Hengrui Therapeutics, Daiichi, Boehringer, Pierre Fabre, and Amgen. Kim reports having consulting/advisory roles at AstraZeneca, Boryung, Hanmi, Eli Lilly, Novartis, Takeda, Sanofi, and Roche/Genentech and receiving a grant from AstraZeneca-KHIDI. Quoix reports receiving grants and personal fees from Bristol-Myers Squibb; personal fees from Chugai; and grants from Roche, Takeda, and Medscape interview during the American Society of Clinical Oncology 2019. Souquet reports receiving grant, personal fee, and nonfinancial support from Novartis. Barlesi reports receiving personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd., Novartis, Merck, Merck Sharp & Dohme, Pierre Fabre, Pfizer, and Takeda. Baik reports receiving grants from LOXO Oncology, Spectrum Pharmaceuticals, Pfizer, Blueprint Medicines, Daiichi Sankyo, AbbVie, Rain Therapeutics, Turning Point Therapeutics, AstraZeneca, Hoosier Caner Research Network, Novartis, Genentech Inc., and personal fees from AstraZeneca, BluePrint Medicine, and Daiichi Sankyo. Villaruz reports receiving grants from Merck, Celgene, Eli Lilly, Genentech, AstraZeneca, Incyte, Rain Therapeutics, Exelixis, Bristol-Myers Squibb, and GlaxoSmithKline, and personal fees from Achilles and Daiichi Sankyo. Kelly acts as advisory for Bristol-Myers Squibb, Novartis, Eli Lilly, AstraZeneca, Merck, Takeda, Daiichi Sankyo, and EMD Serono and reports receiving grants from Eli Lilly and Bristol-Myers Squibb. Zhang reports employment for Novartis. Tan reports employment for Novartis. Gasal reports employment for Novartis. Santarpia reports employment for Novartis. Dr. Johnson reports receiving grants from Cannon Medical Systems, grants and personal fees from Novartis, and personal fees from Hengrui Therapeutics, Daiichi Sankyo, Checkpoint Therapeutics, Lilly, and G1 Therapeutics; has a patent EGFR Mutation Testing with royalties. Hashemi declares no conflict of interest.