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Cocktail & Poster Display session

57P - Clinical characteristics and outcomes in non-small cell lung cancer (NSCLC) with tumour and germline BRCA1/2 mutations

Date

04 Oct 2023

Session

Cocktail & Poster Display session

Presenters

Greydon Arthur

Citation

Annals of Oncology (2023) 8 (suppl_1_S5): 1-55. 10.1016/esmoop/esmoop101646

Authors

G.N.J. Arthur1, S. Sun2

Author affiliations

  • 1 Internal Medicine, Faculty of Medicine, University of British Columbia - Vancouver General Hospital, V5Z 1M9 - Vancouver/CA
  • 2 Division Of Medical Oncology, BC Cancer Agency - Vancouver, V5Z 4E6 - Vancouver/CA

Resources

This content is available to ESMO members and event participants.

Abstract 57P

Background

Expanded use of tumour molecular testing to enable targeted treatment across multiple cancers has increased identification of potential pathogenic germline variants (pPGVs). In NSCLC, BRCA1 and BRCA2 are two potentially targetable pPGVs that are not well described despite BRCA-mutated lung cancer accounting for 1%-14% of cases. This study evaluates the frequency of BRCA1/2-mutated NSCLC identified via tumour sequencing and describes patient and tumour characteristics, family history, clinical course, and germline BRCA mutational status.

Methods

NSCLC patients who underwent tumour testing between January 1, 2018 and June 30, 2021 were identified. Next generation sequencing was used to screen for 46 tumour gene mutations including BRCA1/2, with subsequent referral for germline testing via gene specific intronic polymerase chain reaction amplification if pPGVs were identified.

Results

Of 2784 patients with NSCLC who had tumour sequencing, 44 (1.6%) had pPGVs in BRCA1/2. The majority of patients had metastatic disease at diagnosis (59.1%) and a family history of cancer in a first-degree relative (56.8%), while 34.1% had personal history of a second primary cancer. Frequently co-mutated genes were TP53 (68.2%), KRAS (40.1%), and EGFR (20.5%). Of patients who had confirmatory testing, 60% (12/20) were confirmed germline BRCA1/2 carriers. Patients with stage IV disease at time of diagnosis with germline BRCA1/2 mutation had shortened overall survival (18.7 ± 4.6 months) when compared to the 8 patients with confirmed somatic BRCA1/2 mutation (63.8 ± 21.8 months, p = 0.027).

Conclusions

BRCA1/2 tumour mutations were detected with frequency consistent with prior reports and exhibit high likelihood of associated germline mutation. The observed difference in survival of patients with advanced disease harbouring somatic versus germline mutation warrants further study and highlights the importance of confirmatory germline testing as targeted therapies emerge in order to adequately prognosticate and inform families of at-risk status.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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