Back to Search
Start Over
Immune biomarkers and response to checkpoint inhibition of BRAF V600 and BRAF non-V600 altered lung cancers.
- Source :
-
British journal of cancer [Br J Cancer] 2022 Apr; Vol. 126 (6), pp. 889-898. Date of Electronic Publication: 2021 Dec 28. - Publication Year :
- 2022
-
Abstract
- Background: While 2-4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours.<br />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.<br />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, Pā<ā0.001), 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 (Pā=ā0.25), 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).<br />Conclusions: A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen.<br /> (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- Biomarkers, Tumor genetics
Biomarkers, Tumor immunology
High-Throughput Nucleotide Sequencing
Humans
Mutation
Immune Checkpoint Inhibitors pharmacology
Lung Neoplasms drug therapy
Lung Neoplasms genetics
Lung Neoplasms immunology
Proto-Oncogene Proteins B-raf genetics
Proto-Oncogene Proteins B-raf immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-1827
- Volume :
- 126
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 34963703
- Full Text :
- https://doi.org/10.1038/s41416-021-01679-1