Abstract 1429P
Background
With the rapidly evolving targeted therapy in lung cancer, a study was done to identify a new biomarker HRR gene mutation by precision genomics-based testing and to determine its relationship with immunotherapy biomarkers.
Methods
228 cancer patients underwent the FoundationOne CDx genetic testing for the presence of HRR gene mutation over 3 years. The HRR gene includes ATM, ARID1A, BARD1, BRCA 1/2, BRIP1, CDK12, CHEK1/2, FANCA/E/G, PALB2, PPP2R2A, RAD51B/C/D, RAD54L. PD-L1 (IHC) testing and Next-Generation Sequencing (NGS) testing were done to detect alterations in 324 genes including HRR gene mutation, microsatellite instability (MSI) and tumor mutational burden (TMB). 30 patients with advanced lung cancer who underwent the genetic testing were divided into two groups of HRR gene mutated vs HRR gene wild-type (WT) and tested for statistical significance.
Results
Among 228 cancer patients analyzed, the overall HRR gene mutation prevalence was 26.31% (N=228). In the study population of 30 patients with advanced lung cancer, the age (mean 68.9, SD 8.86 years), 43.33% males (n=13), 56.67% females (n=17), at least one HRR gene mutation was detected in 26.66% (n=8) and 73.33% (n=22) of patients were HRR gene WT. Histopathology was NSCLC in 80% (n=24) and SCLC in 20% (n=6) of patients. The difference in means of TMB (mut/Mb) between HRR gene mutated (Median=7.50, IQR 3.75-21.25) and HRR gene WT (Median=8.00, IQR 5.25-12.25) groups using the Mann-Whitney U test was not statistically significant (P>.99). The comparison of PD-L1 status (P=.23), MSI status (P>.99) between HRR gene mutated and HRR gene WT groups using fisher’s exact test was not statistically significant. Table: 1429P
| HRR genes | (n) | Immunotherapy biomarkers | HRR gene mutated,(n) | HRR gene wild-type,(n) |
| ATM | 2 | TMB ≥10 High | 50% (4) | 31.82% (7) |
| ARID1A | 1 | TMB <10 Low | 50% (4) | 68.18% (15) |
| BARD1 | 1 | MSI-High | 0 | 0 |
| BRCA 1/2 | 1 | MS-Stable | 100% (8) | 100% (22) |
| CDK12 | 1 | PD-L1 TPS% | ||
| FANCA/E/G | 2 | Negative <1% | 75% (6) | 45.45% (10) |
| RAD51B/C/D | 1 | Low 1-49% | 25% (2) | 22.72% (5) |
| BRIP1, CHEK1/2, PALB2, PPP2R2A, RAD54L | 0 | High ≥50% | 0 | 31.82% (7) |
| Precision genomics-based testing | % patients (n=30) | |||
| YES (EGFR, ALK, KRAS G12C) | 16.66% (5) | |||
| NO (Non-targetable biomarkers) | 83.33% (25) | |||
| HRR gene mutated | 32% (8) | |||
| HRR gene WT | 68% (17) | |||
| First-line systemic therapy Chemotherapy(CT)/ Immunotherapy (IO)/ Targeted therapy(TT) | % patients (n=30) | |||
| CT | 30% (9) | |||
| CT + IO | 50% (15) | |||
| IO | 10% (3) | |||
| TT | 10% (3) |
Conclusions
The HRR gene mutation in advanced lung cancer was independent of the predictors for immunotherapy response (TMB, MSI and PD-L1 biomarkers). Further clinical trials are needed to assess the efficacy of combining poly ADP ribose polymerase (PARP) inhibitors with immunotherapy in the future.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Memorial Health System, Belpre, Ohio, United States of America.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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