Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster session 04

1277P - HRD status of patients with early stage non-small cell lung cancer

Date

21 Oct 2023

Session

Poster session 04

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Apostolos Klinakis

Citation

Annals of Oncology (2023) 34 (suppl_2): S732-S745. 10.1016/S0923-7534(23)01265-6

Authors

A. Klinakis1, G. Christopoulou2, A. Voutsina1, G. Vatselas1, K. Potaris3, A. Chalari1, K. Tsilingiri1, I. Vamvakaris4, T. Loupis1, D. Vrachnos1, G. Zachou5, P. Constantoulakis2, A. Kotsakis6, V. Georgoulias7

Author affiliations

  • 1 Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 115 27 - Athens/GR
  • 2 Genomics, Genotypos Science Labs, 115 28 - Athens/GR
  • 3 Thoracic Surgery, "SOTIRIA” General Hospital Athens, 115 27 - Athens/GR
  • 4 Pathology, "SOTIRIA” General Hospital Athens, 115 27 - Athens/GR
  • 5 Medical Oncology, Metropolitan General Hospital of Athens, 155 62 - Cholargos/GR
  • 6 Medical Oncology, University General Hospital of Larissa, 41110 - Larissa/GR
  • 7 Medical Oncology, Hellenic Oncology Research Group (HORG), 11471 - Athens/GR

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 1277P

Background

There is an unmet need for post-surgical therapeutic options in early-stage NSCLC patients. PARP inhibitors (PARPi) have shown efficacy in cancer patients harboring germline or/and somatic BRCA1/BRCA2 mutations and homologous recombination deficiency (HRD). Patient selection for targeted treatment is of crucial importance. Thus, the assessment of HRD status in patients with early-stage NSCLC may pave the way for the use of PARPi in an adjuvant setting.

Methods

Tumor specimens and peripheral blood samples were analyzed for somatic and germ-line mutations with a customized panel of 58 genes. To assess HRD status the genomic scar score (GSS) was calculated using the AmoyDx® HRD Focus Panel or AmoyDx® HRD Complete Panel. The effect of PARP inhibition on tumour growth was assessed in patient-derived xenografts, where RAD51 foci were quantified by immunofluorescence.

Results

Six of 85 patients (59 men/26 women) with operable NSCLC, carried germline mutations in BRCA1 (n=1), BRCA2 (n=1), ATM (n=3), and PALB2 (n=1) genes. Pathogenic somatic mutations were detected in BRCA1 (n=8), BRCA2 (n=9), ATM (n=8), PALB2 (n=3), CHEK1 (n=3), CHEK2 (n=6), RAD50 (n=5) and TP53 (n=49) genes. Based on GSS, 25 (29.4%) patients were characterized as HRD and at least one somatic HRR mutated gene was observed in 15 (57.7%) of them [BRCA1 (n=4), BRCA2 (n=4), ATM (n=3), PALB2 (n=2), CHEK2 (n=1) ]. Preliminary functional experiments in HRP (HR proficient, n=5) and HRD (n=4) PDX and organoids (n=3 and n=3 for HRD and HRP respectively) indicate that HRD tumors present low RAD51 foci count (p=0.03 after damage induction) and favorable response to Olaparib and CDDP.

Conclusions

These data suggest that homologous recombination may be deficient in a substantial proportion of early-stage NSCLC patients, supporting the potential use of PARPi in HRD patients in the adjuvant or maintenance setting.

Clinical trial identification

N/A

Editorial acknowledgement

N/A

Legal entity responsible for the study

The authors.

Funding

Amoy Diagnostics.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.