Use of PARPi among patients with HER2+ve MBC: Results from a real world dataset.

Abstract

e13044 Background: Among individuals with germline mutations in BRCA1/ BRCA2 genes, life-time risk of developing breast cancer is approximately 50%. The majority of these cancers are HER2-ve with a low frequency of HER2+ve breast cancer (2.1%-10% in pts with BRCA1 mutations and 6.8%-13% of pts with BRCA2 mutations) with co-occurrence of BRCA mutation and HER2+ve status being a poor prognostic factor. PARPi have been shown in phase III trials to be effective in HER2-ve BRCA mutation MBC. The objective of this retrospective analysis was to look at the prognostic outcome associated with use of PARPi among pts with HER2 +ve BRCA mutated MBC in the real-world setting. Methods: We utilized a federated network of de-identified health data representing approximately 107 million pt lives available through the TriNetX Research Network. We identified patients with MBC who were treated with PARPi, and pts were assumed to have BRCA mutated MBC if they were recorded with a PARPi. Overall survival (OS) was computed using the Kaplan Meier product limit method. Pts with MBC were defined as having HER2+ve status if they received an anti-HER2 therapy after metastasis, HR+ve if they received endocrine therapy after metatstasis, and triple negative (TNBC) if they did not receive anti-HER2 therapy or endocrine therapy. Results: 1369pts with MBC were treated with PARPi, of whom 77.9%received olaparib. Mean age of pts was 57ys. 546(39.9%), 521(38.1%) and 73(5.3%) pts had TNBC, HR+ve/HER2-ve, and HER2+ve MBC, respectively. Among pts with HER2+ve disease, 35.2% and 74.0% had HR-ve and HR+ve MBC, respectively. Median time to use of PARPi was 7.1m, 15.1m, and 24.0m among pts with TNBC, HR+ve/HER2-ve, and HER2 +ve MBC respectively. Median OS was 44.4m, 47.0m, and 46.7m among pts with TNBC, HR+ve/HER2-ve and HER2+ve MBC respectively. Among pts with HER2+ve disease, median OS was 74.5m and 31.5m among pts with HR+ve and HER-ve disease, respectively (HR=0.27, p=0.0001). 321(23.4%) pts had brain metastases of whom 36.8%, 36.4% and 8.1% had TNBC, HR+ve/HER2-ve and HER2+ve MBC respectively. Among pts with HER2+ve MBC,38.3% received anti HER2 therapy before PARPi, 24.7% received anti HER2 therapy after PARPi and 37.0% received PARPi and anti HER2 therapy concurrently. Among pts with HER2+ve disease, median OS was 44.4m among those who received anti -HER2 therapy on or before PARPi and 93.8m among those who received anti-HER2 therapy after PARPi (HR 0.83, p=0.64).Among pts with brain metastases, median OS was 23.9m, 40.0m and 40.2m among pts with TNBC, HR+ve/HER-ve and HER2+ve MBC respectively. Conclusions: To our knowledge this is the first real world data set to report on the prognostic outcome of pts with HER2+ve BRCA mutated MBC. When PARPi inhibitors are given median OS is similar among the three subtypes of breast cancer. Although not significant, there appears to be a trend towards improved OS with earlier use of PARPi among patients with HER2+ve BRCA mutated MBC.