2022 World Conference on Lung Cancer (ePosters)-EP08.02-074. Impact of Germline BRCA1/2 Alterations on EGFR Mutant Advanced Non-small Cell Lung Cancer Outcomes

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The impact of incidental pathogenic germline variants (iPGVs) in the BRCA1/2 genes on the outcomes of patients with advanced non-small cell lung cancer (NSCLC) who receive EGFR targeted therapy is not well understood. In this study, the researchers used real-world evidence to explore the impact of iPGV findings in BRCA1/2 on outcomes in patients with EGFR mutant advanced NSCLC who were treated with EGFR monotherapy. The results showed a non-significant trend suggesting that patients with both germline BRCA alterations (gBRCA) and EGFR mutant NSCLC treated with EGFR monotherapy may have subpar outcomes compared to gBRCA-matched controls. The estimated progression-free survival (PFS) was likely 9-18 months for gBRCA patients and 12-25 months for gBRCA- patients. <br /><br />It is important to further study and understand the significance of gBRCA findings in NSCLC patients with and without these alterations. While combination therapy, such as PARP inhibition, may be beneficial for patients who are both EGFR mutant and gBRCA, studies should also assess how gBRCA alterations impact patient outcomes even if they are not directly driving tumorigenesis. <br /><br />The study used real-world data from the Guardant Health database, which includes aggregated commercial payer health claims and de-identified records from over 190,000 patients with Guardant360 results. The analysis included 32 patients with gBRCA who received EGFR monotherapy and a matched control cohort of 160 patients without gBRCA alterations. The outcomes assessed were real-world time to treatment discontinuation (rwTTD) and real-world time to next treatment (rwTTNT) as proxies for progression-free survival. The results showed that patients with gBRCA treated with EGFR monotherapy had shorter rwTTD and rwTTNT, but similar overall survival (OS) compared to control patients without gBRCA alterations, although these findings did not reach statistical significance. <br /><br />In conclusion, this study provides insights into the impact of germline BRCA alterations on the outcomes of patients with EGFR mutant advanced NSCLC receiving EGFR monotherapy. However, further studies and data maturation are needed to establish the significance of gBRCA findings in this patient population.

Asset Subtitle

Jyoti D. Patel

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Speaker Jyoti D. Patel

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

incidental pathogenic germline variants

BRCA1/2 genes

advanced non-small cell lung cancer

NSCLC

EGFR targeted therapy

real-world evidence

EGFR monotherapy

progression-free survival

germline BRCA alterations

PARP inhibition