F Aya1,2, A Fernandez-Martinez3,4, L Gaba3,4, I Victoria3,4, M Tosca3,4, E Pineda3,4, P Gascon3, A Prat3,4, A Arance3,4. 1. Department of Medical Oncology, Hospital Clínic, Barcelona, Spain. faya@clinic.ub.es. 2. Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. faya@clinic.ub.es. 3. Department of Medical Oncology, Hospital Clínic, Barcelona, Spain. 4. Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Abstract
PURPOSE: Immunotherapy (IT) agents and BRAF inhibitors (BRAFi) are effective treatments for patients with advanced BRAF-mutant melanoma although the optimal sequence remains to be elucidated. The aim of this study was to compare the outcomes of two different cohorts of patients treated with BRAFi first, then IT or the reverse sequence. PATIENTS AND METHODS: This is a retrospective study on two groups of patients: a cohort was treated first with BRAFi followed by immunotherapy (BRAFi-IT) and the other cohort with the reverse sequence (IT-BRAFi). Baseline characteristics and clinical outcomes were compared between the two cohorts. RESULTS: A total of 25 patients were included in the study. Sixteen patients were given BRAFi-IT sequence and nine received IT-BRAFi sequence. No differences were observed in the characteristics of patients prior to each treatment between cohorts. Objective response rate (ORR) achieved by BRAFi were not different among groups. ORR achieved by IT was higher when administered after BRAFi (43.8 vs 0 %). Survival rates at 1-2 years were similar in both cohorts and median overall survival was not different for BRAFi-IT and IT-BRAFi (log rank test p = 0.97). CONCLUSIONS: No differences were observed in OS between the two cohorts. These results support the indistinct use of IT or BRAFi as initial treatment in patients with metastatic BRAF-mutant melanoma, although higher rate of response to IT was observed when administered after BRAFi. Prospective randomized clinical trials are needed on this issue.
PURPOSE: Immunotherapy (IT) agents and BRAF inhibitors (BRAFi) are effective treatments for patients with advanced BRAF-mutant melanoma although the optimal sequence remains to be elucidated. The aim of this study was to compare the outcomes of two different cohorts of patients treated with BRAFi first, then IT or the reverse sequence. PATIENTS AND METHODS: This is a retrospective study on two groups of patients: a cohort was treated first with BRAFi followed by immunotherapy (BRAFi-IT) and the other cohort with the reverse sequence (IT-BRAFi). Baseline characteristics and clinical outcomes were compared between the two cohorts. RESULTS: A total of 25 patients were included in the study. Sixteen patients were given BRAFi-IT sequence and nine received IT-BRAFi sequence. No differences were observed in the characteristics of patients prior to each treatment between cohorts. Objective response rate (ORR) achieved by BRAFi were not different among groups. ORR achieved by IT was higher when administered after BRAFi (43.8 vs 0 %). Survival rates at 1-2 years were similar in both cohorts and median overall survival was not different for BRAFi-IT and IT-BRAFi (log rank test p = 0.97). CONCLUSIONS: No differences were observed in OS between the two cohorts. These results support the indistinct use of IT or BRAFi as initial treatment in patients with metastatic BRAF-mutant melanoma, although higher rate of response to IT was observed when administered after BRAFi. Prospective randomized clinical trials are needed on this issue.
Authors: Caroline Robert; Georgina V Long; Benjamin Brady; Caroline Dutriaux; Michele Maio; Laurent Mortier; Jessica C Hassel; Piotr Rutkowski; Catriona McNeil; Ewa Kalinka-Warzocha; Kerry J Savage; Micaela M Hernberg; Celeste Lebbé; Julie Charles; Catalin Mihalcioiu; Vanna Chiarion-Sileni; Cornelia Mauch; Francesco Cognetti; Ana Arance; Henrik Schmidt; Dirk Schadendorf; Helen Gogas; Lotta Lundgren-Eriksson; Christine Horak; Brian Sharkey; Ian M Waxman; Victoria Atkinson; Paolo A Ascierto Journal: N Engl J Med Date: 2014-11-16 Impact factor: 91.245
Authors: Caroline Robert; Luc Thomas; Igor Bondarenko; Steven O'Day; Jeffrey Weber; Claus Garbe; Celeste Lebbe; Jean-François Baurain; Alessandro Testori; Jean-Jacques Grob; Neville Davidson; Jon Richards; Michele Maio; Axel Hauschild; Wilson H Miller; Pere Gascon; Michal Lotem; Kaan Harmankaya; Ramy Ibrahim; Stephen Francis; Tai-Tsang Chen; Rachel Humphrey; Axel Hoos; Jedd D Wolchok Journal: N Engl J Med Date: 2011-06-05 Impact factor: 91.245
Authors: F Stephen Hodi; Steven J O'Day; David F McDermott; Robert W Weber; Jeffrey A Sosman; John B Haanen; Rene Gonzalez; Caroline Robert; Dirk Schadendorf; Jessica C Hassel; Wallace Akerley; Alfons J M van den Eertwegh; Jose Lutzky; Paul Lorigan; Julia M Vaubel; Gerald P Linette; David Hogg; Christian H Ottensmeier; Celeste Lebbé; Christian Peschel; Ian Quirt; Joseph I Clark; Jedd D Wolchok; Jeffrey S Weber; Jason Tian; Michael J Yellin; Geoffrey M Nichol; Axel Hoos; Walter J Urba Journal: N Engl J Med Date: 2010-06-05 Impact factor: 91.245
Authors: Allison Ackerman; Oliver Klein; David F McDermott; Wei Wang; Nageatte Ibrahim; Donald P Lawrence; Anasuya Gunturi; Keith T Flaherty; F Stephen Hodi; Richard Kefford; Alexander M Menzies; Michael B Atkins; Georgina V Long; Ryan J Sullivan Journal: Cancer Date: 2014-02-27 Impact factor: 6.860
Authors: Jenny N Poynter; James T Elder; Douglas R Fullen; Rajan P Nair; Maria S Soengas; Timothy M Johnson; Bruce Redman; Nancy E Thomas; Stephen B Gruber Journal: Melanoma Res Date: 2006-08 Impact factor: 3.599
Authors: E Elizabeth Patton; Hans R Widlund; Jeffery L Kutok; Kamden R Kopani; James F Amatruda; Ryan D Murphey; Stephane Berghmans; Elizabeth A Mayhall; David Traver; Christopher D M Fletcher; Jon C Aster; Scott R Granter; A Thomas Look; Charles Lee; David E Fisher; Leonard I Zon Journal: Curr Biol Date: 2005-02-08 Impact factor: 10.834
Authors: Dennie T Frederick; Adriano Piris; Alexandria P Cogdill; Zachary A Cooper; Cecilia Lezcano; Cristina R Ferrone; Devarati Mitra; Andrea Boni; Lindsay P Newton; Chengwen Liu; Weiyi Peng; Ryan J Sullivan; Donald P Lawrence; F Stephen Hodi; Willem W Overwijk; Gregory Lizée; George F Murphy; Patrick Hwu; Keith T Flaherty; David E Fisher; Jennifer A Wargo Journal: Clin Cancer Res Date: 2013-01-10 Impact factor: 12.531
Authors: Marta Polkowska; Paweł Ekk-Cierniakowski; Edyta Czepielewska; Wojciech Wysoczański; Wojciech Matusewicz; Małgorzata Kozłowska-Wojciechowska Journal: J Cancer Res Clin Oncol Date: 2017-06-12 Impact factor: 4.553
Authors: Carl M Thielmann; Johanna Matull; Anne Zaremba; Rajmohan Murali; Eleftheria Chorti; Georg Lodde; Philipp Jansen; Rudolf Herbst; Patrick Terheyden; Jochen Utikal; Claudia Pföhler; Jens Ulrich; Alexander Kreuter; Peter Mohr; Ralf Gutzmer; Friedegund Meier; Edgar Dippel; Michael Weichenthal; Julia Kretz; Inga Möller; Antje Sucker; Annette Paschen; Elisabeth Livingstone; Lisa Zimmer; Eva Hadaschik; Selma Ugurel; Dirk Schadendorf; Klaus G Griewank Journal: Eur J Cancer Date: 2021-12-20 Impact factor: 10.002
Authors: A Berrocal; A Arance; V E Castellon; L de la Cruz; E Espinosa; M G Cao; J L G Larriba; I Márquez-Rodas; A Soria; S M Algarra Journal: Clin Transl Oncol Date: 2017-11-07 Impact factor: 3.405
Authors: Paolo A Ascierto; Antoni Ribas; James Larkin; Grant A McArthur; Karl D Lewis; Axel Hauschild; Keith T Flaherty; Edward McKenna; Qian Zhu; Yong Mun; Brigitte Dréno Journal: J Transl Med Date: 2020-08-03 Impact factor: 5.531