James Larkin1, Michael P Brown2, Ana M Arance3, Axel Hauschild4, Paola Queirolo5, Michele Del Vecchio6, Paolo A Ascierto7, Ivana Krajsová8, Jacob Schachter9, Bart Neyns10, Claus Garbe11, Vanna Chiarion Sileni12, Mario Mandalà13, Helen Gogas14, Enrique Espinosa15, Geke Hospers16, Paul Lorigan17, Marta Nyakas18, Alex Guminski19, Gabriela Liszkay20, Piotr Rutkowski21, Wilson Miller22, Margarita Donica23, Martina Makrutzki23, Christian Blank24. 1. The Royal Marsden NHS Foundation Trust, London, UK. Electronic address: james.larkin@rmh.nhs.uk. 2. Cancer Clinical Trials Unit, Royal Adelaide Hospital, Centre for Cancer Biology, SA Pathology, University of South Australia, Adelaide, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, Australia. 3. Department of Medical Oncology, Hospital Clinic Barcelona, Barcelona, Spain. 4. Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany. 5. UOC Oncologia Medica, Istituto di Ricerca e Cura a Carattere Scientifico, San Martino-IST, Genova, Italy. 6. Department of Medical Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy. 7. Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy. 8. Dermatovenerologická klinika, University Hospital Prague, Charles University, First Medical Faculty, Prague, Czech Republic. 9. Chaim Sheba Medical Centre, Oncology Institute, Ramat-Gan, Israel. 10. Afdelingshoofd, Medische Oncologie, Brussels, Belgium. 11. Department of Dermatology, University Medical Center, Tuebingen, Germany. 12. Istituto Oncologico Veneto, Padua, Italy. 13. Papa Giovanni XXIII Hospital, Bergamo, Italy. 14. University of Athens, Athens, Greece. 15. Hospital La Paz, Madrid, Spain. 16. University Medical Centre Groningen, Groningen, the Netherlands. 17. Christie NHS Foundation Trust, Manchester, UK. 18. Oslo University Hospital, Oslo, Norway. 19. Melanoma Institute Australia, Royal North Shore Hospital, University of Sydney, Sydney, Australia. 20. Department of Dermatooncology, National Institute of Oncology, Budapest, Hungary. 21. Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland. 22. McGill University, Segal Cancer Centre, Montreal, Quebec, Canada. 23. F. Hoffmann-La Roche Ltd, Basel, Switzerland. 24. The Netherlands Cancer Institute, Amsterdam, the Netherlands. Electronic address: c.blank@nki.nl.
Abstract
BACKGROUND: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. PATIENTS AND METHODS: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAFV600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397). RESULTS: Between March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ≥1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib. CONCLUSIONS: Final results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAFV600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work.
BACKGROUND: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. PATIENTS AND METHODS: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAFV600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397). RESULTS: Between March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ≥1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib. CONCLUSIONS: Final results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAFV600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work.
Authors: Mbathio Dieng; Robin M Turner; Sarah J Lord; Andrew J Einstein; Alexander M Menzies; Robyn P M Saw; Omgo E Nieweg; John F Thompson; Rachael L Morton Journal: Int J Environ Res Public Health Date: 2022-02-17 Impact factor: 3.390
Authors: Mbathio Dieng; Sarah J Lord; Robin M Turner; Omgo E Nieweg; Alexander M Menzies; Robyn P M Saw; Andrew J Einstein; Louise Emmett; John F Thompson; Serigne N Lo; Rachael L Morton Journal: Ann Surg Oncol Date: 2022-02-10 Impact factor: 5.344