Abstract 17P
Background
Homologous recombination deficiency (HRD) can predict sensitivity to platinum-based chemotherapy and PARP-inhibitors in cancer patients. HRD testing is currently used clinically to decide the optimal course of treatment of high-grade ovarian cancer, but the HRD score may be relevant in other diagnoses. The purpose of this study was to assess changes in HRD status in consecutive tumor biopsies from late-stage, solid tumor cancer patients.
Methods
Genomic tumor profiles obtained in the Copenhagen Prospective Personalized Oncology study (CoPPO: NCT02290522) at the Phase 1 Unit, Department of Oncology, Rigshospitalet over a 10-year period (August 2013 until April 2023) were retrospectively analyzed. All patients with >1 tumor tissue sample and with available genomic tumor profile were included. Genomic tumor profiles are based on various analyses including whole exome or genome sequencing, RNA-sequencing and SNP-array. HRD scores were assessed on SNP-array based on the method described in Telli et al., 2016. The score is based on the unweighted sum of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale transitions (LST). A score of ≥42 is considered positive.
Results
In total 109 patients (62% female) were included across 24 different cancer diagnoses. The most frequent diagnoses were colorectal cancer (n=26, 24%), breast cancer (n=20, 18%) and non-small cell lung cancer (n=17, 16%). An increase in HRD score from first tumor biopsy to last tumor biopsy was found in 57 patients while 29 patients had a decrease in HRD score, with 23 patients unchanged. On first biopsy 67 (61.5%) patients were HRD negative and 42 (38.5%) were HRD positive. A clinically significant change in HRD status with Telli score crossing the cut point of ≥42 from first to last biopsy was observed in 18 patients: 13 went from negative to positive HRD whilst 5 went from positive to negative HRD status.
Conclusions
In our cohort 18 patients (17%) changed HRD status from first to last tumor biopsy. This suggests that HRD may be a dynamic biomarker, and its status can change in some late-stage cancer patients. This could have implications for patients with cancer types who may be considered for treatment with PARP-inhibitors based on a positive HRD score.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
I.K. Buhl: Financial Interests, Personal, Stocks/Shares: Aida Oncology Aps. I. Spanggaard: Financial Interests, Institutional, Invited Speaker: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer; Non-Financial Interests, Personal, Principal Investigator: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer. M. Hoejgaard: Financial Interests, Personal, Other, Advisory role for various diagnostic companies/investors: LingoMedical; Financial Interests, Personal, Stocks/Shares, Stocks, U.N. Lassen: Financial Interests, Personal, Advisory Board: Bayer, Novartis; Financial Interests, Institutional, Research Grant: Roche, BMS, Pfizer, GSK, Lilly, Incyte. K.S. Rohrberg: Financial Interests, Personal, Invited Speaker: Bayer, Amgen, MSD, GSK; Financial Interests, Personal, Advisory Board: AbbVie, Genmab; Financial Interests, Institutional, Invited Speaker, Compensation for conduction of clinical trial: Lilly, Roche/Genentech, Bristol Myers Squibb, Symphogen, Pfizer, Novartis, Alligator Bioscience, Genmab, BioInvent, Monta Bioscience, Amgen, Navire; Financial Interests, Institutional, Other, Compensation for conduction of clinical trial: Bayer, Incyte, Puma Biotechnology, Orion Clinical. All other authors have declared no conflicts of interest.