BACKGROUND: While 2-4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours. METHODS: Clinical and genomic data were collected from 5945 patients with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020. RESULTS: In total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I-III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17-6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS). CONCLUSIONS: A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen.
BACKGROUND: While 2-4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours. METHODS: Clinical and genomic data were collected from 5945 patients with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020. RESULTS: In total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I-III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17-6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS). CONCLUSIONS: A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen.
Authors: Paul K Paik; Maria E Arcila; Michael Fara; Camelia S Sima; Vincent A Miller; Mark G Kris; Marc Ladanyi; Gregory J Riely Journal: J Clin Oncol Date: 2011-04-11 Impact factor: 44.544
Authors: Emmet J Jordan; Hyunjae R Kim; Maria E Arcila; David Barron; Debyani Chakravarty; JianJiong Gao; Matthew T Chang; Andy Ni; Ritika Kundra; Philip Jonsson; Gowtham Jayakumaran; Sizhi Paul Gao; Hannah C Johnsen; Aphrothiti J Hanrahan; Ahmet Zehir; Natasha Rekhtman; Michelle S Ginsberg; Bob T Li; Helena A Yu; Paul K Paik; Alexander Drilon; Matthew D Hellmann; Dalicia N Reales; Ryma Benayed; Valerie W Rusch; Mark G Kris; Jamie E Chaft; José Baselga; Barry S Taylor; Nikolaus Schultz; Charles M Rudin; David M Hyman; Michael F Berger; David B Solit; Marc Ladanyi; Gregory J Riely Journal: Cancer Discov Date: 2017-03-23 Impact factor: 39.397
Authors: Stephanie Cardarella; Atsuko Ogino; Mizuki Nishino; Mohit Butaney; Jeanne Shen; Christine Lydon; Beow Y Yeap; Lynette M Sholl; Bruce E Johnson; Pasi A Jänne Journal: Clin Cancer Res Date: 2013-07-05 Impact factor: 12.531
Authors: Anya M Litvak; Paul K Paik; Kaitlin M Woo; Camelia S Sima; Matthew D Hellmann; Maria E Arcila; Marc Ladanyi; Charles M Rudin; Mark G Kris; Gregory J Riely Journal: J Thorac Oncol Date: 2014-11 Impact factor: 15.609
Authors: Helen Davies; Graham R Bignell; Charles Cox; Philip Stephens; Sarah Edkins; Sheila Clegg; Jon Teague; Hayley Woffendin; Mathew J Garnett; William Bottomley; Neil Davis; Ed Dicks; Rebecca Ewing; Yvonne Floyd; Kristian Gray; Sarah Hall; Rachel Hawes; Jaime Hughes; Vivian Kosmidou; Andrew Menzies; Catherine Mould; Adrian Parker; Claire Stevens; Stephen Watt; Steven Hooper; Rebecca Wilson; Hiran Jayatilake; Barry A Gusterson; Colin Cooper; Janet Shipley; Darren Hargrave; Katherine Pritchard-Jones; Norman Maitland; Georgia Chenevix-Trench; Gregory J Riggins; Darell D Bigner; Giuseppe Palmieri; Antonio Cossu; Adrienne Flanagan; Andrew Nicholson; Judy W C Ho; Suet Y Leung; Siu T Yuen; Barbara L Weber; Hilliard F Seigler; Timothy L Darrow; Hugh Paterson; Richard Marais; Christopher J Marshall; Richard Wooster; Michael R Stratton; P Andrew Futreal Journal: Nature Date: 2002-06-09 Impact factor: 49.962
Authors: Alessandro Di Federico; Andrea De Giglio; Francesco Gelsomino; Dario De Biase; Francesca Giunchi; Arianna Palladini; Francesca Sperandi; Barbara Melotti; Andrea Ardizzoni Journal: Cancers (Basel) Date: 2022-07-17 Impact factor: 6.575