David Planchard1, Benjamin Besse1, Harry J M Groen2, Sayed M S Hashemi3, Julien Mazieres4, Tae Min Kim5, Elisabeth Quoix6, Pierre-Jean Souquet7, Fabrice Barlesi8, Christina Baik9, Liza C Villaruz10, Ronan J Kelly11, Shirong Zhang12, Monique Tan12, Eduard Gasal12, Libero Santarpia13, Bruce E Johnson14. 1. Department of Medical Oncology, Gustave Roussy, Villejuif, France. 2. Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands. 3. Department of Pulmonary Medicine, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands. 4. Thoracic Oncology Department, Hospital Larrey, Toulouse, France. 5. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. 6. Department of Chest Diseases, University Hospital of Strasbourg, Strasbourg, France. 7. Department of Pneumonology and Thoracic Oncology, Hôpital de Jour, Pierre Bénite, France. 8. Department of Medical Oncology, Gustave Roussy, Villejuif, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Aix-Marseille University, Marseille, France. 9. Department of Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington. 10. Division of Hematology/Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania. 11. Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas. 12. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. 13. Novartis Pharma AG, Basel, Switzerland. 14. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Electronic address: bruce_johnson@dfci.harvard.edu.
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.
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.
Authors: Anna Michelotti; Marco de Scordilli; Elisa Bertoli; Elisa De Carlo; Alessandro Del Conte; Alessandra Bearz Journal: Int J Mol Sci Date: 2022-06-17 Impact factor: 6.208
Authors: Bruce E Johnson; Christina S Baik; Julien Mazieres; Harry J M Groen; Barbara Melosky; Jürgen Wolf; Fatemeh Asad Zadeh Vosta Kolaei; Wen-Hsing Wu; Stefanie Knoll; Meryem Ktiouet Dawson; Adam Johns; David Planchard Journal: JTO Clin Res Rep Date: 2022-04-06