J Mazieres1, C Cropet2, L Montané2, F Barlesi3, P J Souquet4, X Quantin5, C Dubos-Arvis6, J Otto7, L Favier8, V Avrillon9, J Cadranel10, D Moro-Sibilot11, I Monnet12, V Westeel13, J Le Treut14, E Brain15, J Trédaniel16, M Jaffro17, S Collot17, G R Ferretti18, C Tiffon19, C Mahier-Ait Oukhatar20, J Y Blay21. 1. Thoracic Oncology Unit, IFCT (Intergroupe Français de Cancérologie Thoracique), Respiratory Disease Department, Larrey Hospital, CHU Toulouse, Université Paul Sabatier, Toulouse, France. Electronic address: mazieres.j@chu-toulouse.fr. 2. Direction of Clinical Research and Innovation, Biostatistics Department, Centre Léon Bérard, Lyon, France. 3. Multidisciplinary Oncology & Therapeutic Innovations Department, IFCT, Aix-Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France. 4. Thoracic Oncology Department, IFCT, Hospices Civils de Lyon, CH Lyon Sud, Pierre Bénite, France. 5. Respiratory Diseases Department, Hôpital Arnaud de Villeneuve, Montpellier, France. 6. Pneumology Department, Centre François Baclesse, Caen, France. 7. Department of Medicine, Centre Antoine Lacassagne, Nice, France. 8. Oncology Department, Centre Georges François Leclerc, Dijon, France. 9. Centre Léon Bérard & Centre de Recherche en Cancérologie de Lyon & Université Claude Bernard Lyon I, Lyon, France. 10. Pneumology Department, IFCT, Hôpital Tenon APHP and GRC #4 Theranoscan, Sorbonne Université, Paris, France. 11. IFCT, University Pneumology Clinic, Pôle Thorax et Vaisseaux, CHU Grenoble Alpes, Grenoble, France. 12. Pneumology Department, Centre Hospitalier Intercommunal, Créteil, France. 13. Pneumology Department, IFCT, Hôpital Jean Minjoz, CHU Besançon, Besançon, France. 14. Respiratory Diseases Department, Centre Hospitalier Intercommunal Aix Pertuis, Aix en Provence, France. 15. Department of Medical Oncology, Institut Curie/Saint-Cloud, Saint-Cloud, France. 16. Groupe Hospitalier Paris Saint Joseph, Université Paris Descartes, Sorbonne Paris Cité Unité INSERM UMR-S 1124, Paris, France. 17. Radiology and Medical Imagery Department, Hôpital Rangueil-Larrey, CHU Toulouse, Toulouse, France. 18. Radiology and Medical Imagery Department, CHU Grenoble Alpes & Université Grenoble Alpes, Grenoble, France. 19. French National Cancer Institute, Boulogne-Billancourt, France. 20. Research and Development UNICANCER, Paris, France. 21. Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, LYRICAN (NCa_INSERM_DGOS_12563), Université Claude Bernard Lyon I, Lyon, France.
Abstract
BACKGROUND: BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS: Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION: Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02304809.
BACKGROUND:BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS: Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION: Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02304809.
Authors: Syed N Aziz; Lucia Proano; Claudio Cruz; Maria Gabriela Tenemaza; Gustavo Monteros; Gashaw Hassen; Aakash Baskar; Jennifer M Argudo; Jonathan B Duenas; Stephanie P Fabara Journal: Cureus Date: 2022-06-14
Authors: Yonina R Murciano-Goroff; Terry Pak; Sebastian Mondaca; Jessica R Flynn; Joseph Montecalvo; Natasha Rekhtman; Darragh Halpenny; Andrew J Plodkowski; Stephanie L Wu; Mark G Kris; Paul K Paik; Gregory J Riely; Helena A Yu; Charles M Rudin; Matthew D Hellmann; Josiah D Land; Larry W Buie; Glenn Heller; Piro Lito; Rona Yaeger; Alexander Drilon; Dazhi Liu; Bob T Li; Michael Offin Journal: Br J Cancer Date: 2021-12-28 Impact factor: 9.075
Authors: Tiffany Tsang; Xingxing Gu; Caroline I Davis; Jessica M Posimo; Zoey A Miller; Donita C Brady Journal: Mol Cancer Res Date: 2022-07-06 Impact factor: 6.333