Abstract 1351P
Background
There is a paucity of data regarding the prevalence of pathogenic BRCA variants among non-small-cell lung cancer (NSCLC) patients, and the role of BRCA status as a prognostic and predictive biomarker in this setting. Our objective was to assess the impact of tumor BRCA status on the disease course of NSCLC patients and response to therapy.
Methods
A retrospective study including consecutive NSCLC patients for whom Next Generation Sequencing (NGS) was performed between 01/2015-12/2019. Pathogenicity of identified variants was determined according to ACMG guidelines.
Results
Of 415 patients for which NGS data was available (54% tissue, 41% liquid, 5% undetermined), 101 (24.3%) patients had a documented BRCA variant (mBRCA). 3.7% (14/415) harboured a pathogenic/likely pathogenic variant (pBRCA). 0.96% (4/415) had a suspected germline variant. pBRCA patients were compared against 183 BRCA-wildtype (wtBRCA) patients for which clinical data was available (Table). Age at diagnosis was significantly lower in the pBRCA group (p=0.033; 95% CI 0.286-6.199). There was a trend towards a higher proportion of male patients in the pBRCA group (78.6% vs 51.9%; p=0.054). The proportion of never-smokers in the pBRCA group was higher (46.2% vs 35.6%) however this did not reach statistical significance. Median overall survival was not significantly different between the groups (20.73 months for wtBRCA vs 41.4 months for pBRCA; p=0.252). pBRCA patients (n=4) had a significantly longer median PFS under first line chemo-immunotherapy compared with wtBRCA (n=19) (17 months vs 4.8 months; p=0.023). Table: 1351P
| wtBRCA (n=183) | pBRCA (n=14) | ||
| Sex | 51.9% (95/183) M 48.1% (88/183) F | 78.6% (11/14) M 21.4% (3/14) F | p=0.054 |
| Age at diagnosis (y) (mean[sd]) | 67.5 (11.6) | 64.3 (4.3) | p=0.033 95% CI 0.286-6.199 |
| Never smokers | 35.6% (62/174) | 46.2% (6/14) | p=0.447 |
| Histology | 77% (141/183) Adenocarcinoma 4.4% (8/183) Squamous 1.6% (3/183) Neuroendocrine 16.9% (31/183) Other / Mixed / Unknown | 85.7% (12/14) Adenocarcinoma 0% Squamous 0% Neuroendocrine 14.3% (2/14) Other/Mixed/Unknown | p=0.796 |
| Overall survival (m) (median[sd]) | 20.73 (1.7) | 41.1(1.855) | p=0.252 |
| PFS under first-line chemo-immunotherapy (m) (median[sd]) | 4.8 (0.8) | 17(7.7) | p=0.023 |
Conclusions
NSCLC patients whose tumors harbour pathogenic BRCA mutations exhibit a prolonged PFS under first-line chemo-immunotherapy compared with wtBRCA. Furthermore, pBRCA patients are younger, and there is a trend towards a higher proportion of male sex and never-smokers in this subgroup of NSCLC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.