(162) Incidence of PARP Inhibitor Toxicities Between Germline Versus Somatic Homologous Recombination Mutations

Poster Abstract: Background/

Objectives:
Genetic testing in gynecologic, breast, pancreatic, and prostate cancers is common. While the efficacy of PARP inhibitors (PARPi) has been studied and shown to be comparable between germline and somatic homologous recombination deficiency (HRD) mutations, toxicity differences are less established. Homologous recombination genes are differentially expressed in tissues in immune cells, suggesting that patients with germline mutations may have a different toxicity profile. The most common PARPi adverse events are anemia, neutropenia, and fatigue; the most common grade 3-4 event is anemia which usually improves after dose reductions. The purpose of the study is to determine if there is a difference in PARPi toxicities between patients harboring germline and somatic HRD mutations.

Methods:
This was a retrospective cohort study of PARPi utilization at a single comprehensive cancer center from June 5, 2021 to July 26, 2023 obtained from electronic health records. Patients were included if they were 18 years of age or older, on a PARPi in the study period, and had genetic testing performed. Patients were excluded if the PARPi was discontinued due to an external factor such as cost or if they were taking a PARPi as part of a research study. A total of 76 patients were included in the analysis, of which 33 had a germline mutation and 43 had a somatic mutation which was not identified in the germline. The primary endpoint was a composite of the frequency of dose adjustment, discontinuation, or holding due to toxicities. Secondary endpoints were 6-month progression free survival from start of therapy, 12-month overall survival from start of therapy, frequency of secondary malignancies, number of dose reductions, and toxicity that led to dose adjustment, discontinuation, or hold. Demographic information including sex assigned at birth, age at start of therapy, obesity status, and race was collected. Descriptive statistics and chi square/fisher exact test were used to analyze the demographics and endpoints. Kaplan Meier and Cox proportional hazard were used to analyze survival.

Results/Conclusion/

Discussion: Data analysis is ongoing. Results and conclusions will be presented at the 2024 Hematology/Oncology Pharmacy Association Conference.

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