Author(s): Gregory J. Riely, MD, PhD1; Egbert F. Smit, MD, PhD2; Myung-Ju Ahn, MD, PhD3; Enriqueta Felip, MD, PhD4; Suresh S. Ramalingam, MD5; Anne Tsao, MD6; Melissa Johnson, MD7; Francesco Gelsomino, MD8; Raymond Esper, MD, PhD9; Ernest Nadal, MD, PhD10; Michael Offin, MD1; Mariano Provencio, MD, PhD11; Jeffrey Clarke, MD12; Maen Hussain, MD9; Gregory A. Otterson, MD13; Ibiayi Dagogo-Jack, MD14; Jonathan W. Goldman, MD15; Daniel Morgensztern, MD16; Ann Alcasid, BA17; Tiziana Usari, BSc18; Paul Wissel, MD19; Keith Wilner, PhD20; Nuzhat Pathan, PhD20; Svitlana Tonkovyd, MD21; and Bruce E. Johnson, MD22
PURPOSE
The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAFV600E/K-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600E-mutant metastatic non–small-cell lung cancer (NSCLC).
METHODS
In this ongoing, open-label, single-arm, phase II study, patients with BRAFV600E-mutant metastatic NSCLC received oral encorafenib 450 mg once daily plus binimetinib 45 mg twice daily in 28-day cycles. The primary end point was confirmed objective response rate (ORR) by independent radiology review (IRR). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival, time to response, and safety.
RESULTS
At data cutoff, 98 patients (59 treatment-naïve and 39 previously treated) with BRAFV600E-mutant metastatic NSCLC received encorafenib plus binimetinib. Median duration of treatment was 9.2 months with encorafenib and 8.4 months with binimetinib. ORR by IRR was 75% (95% CI, 62 to 85) in treatment-naïve and 46% (95% CI, 30 to 63) in previously treated patients; median DOR was not estimable (NE; 95% CI, 23.1 to NE) and 16.7 months (95% CI, 7.4 to NE), respectively. DCR after 24 weeks was 64% in treatment-naïve and 41% in previously treated patients. Median PFS was NE (95% CI, 15.7 to NE) in treatment-naïve and 9.3 months (95% CI, 6.2 to NE) in previously treated patients. The most frequent treatment-related adverse events (TRAEs) were nausea (50%), diarrhea (43%), and fatigue (32%). TRAEs led to dose reductions in 24 (24%) and permanent discontinuation of encorafenib plus binimetinib in 15 (15%) patients. One grade 5 TRAE of intracranial hemorrhage was reported. Interactive visualization of the data presented in this article is available at the PHAROS dashboard (https://clinical-trials.dimensions.ai/pharos/).
CONCLUSION
For patients with treatment-naïve and previously treated BRAFV600E-mutant metastatic NSCLC, encorafenib plus binimetinib showed a meaningful clinical benefit with a safety profile consistent with that observed in the approved indication in melanoma.
Author Affiliations
1Memorial Sloan Kettering Cancer Center, New York, NY;2Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, the Netherlands;3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;4Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain;5Winship Cancer Institute of Emory University, Atlanta, GA;6MD Anderson Cancer Center, Houston, TX;7Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN;8Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;9Florida Cancer Specialists, Fort Myers, FL;10Medical Oncology, Catalan Institute of Oncology, Barcelona, Spain;11Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain;12Duke Cancer Center, Durham, NC;13Ohio State University Comprehensive Cancer Center, Columbus, OH;14Massachusetts General Hospital, Boston, MA;15David Geffen School of Medicine at UCLA, Los Angeles, CA;16Washington University School of Medicine, St Louis, MO;17Pfizer, Collegeville, PA;18Pfizer, Milan, Italy;19Pfizer, New York, NY;20Pfizer, La Jolla, CA;21Pfizer, Warsaw, Poland;22Dana-Farber Cancer Institute, Boston, MA
