BACKGROUND: Germline breast cancer susceptibility gene 1/2 - (gBRCA1/2) mutated breast cancer (BC) represents ~5% of all BC. Historically, chemotherapy (CT) and endocrine-based therapy (EBT) have been commonly used in HER2- advanced BC (ABC) patients (pts) with BRCA1/2 mutations (BRCA1/2mut). Between 2015–2018, cyclin-dependent kinase 4/6 inhibitors and poly ADP-ribose polymerases inhibitors (PARPi) became available as targeted therapy for some pts with ABC, including HER2- gBRCA1/2 ABC. With the changing landscape, understanding treatment patterns and associated adverse events (AEs) may inform treatment choices.
OBJECTIVE: To assess real-world treatment patterns and associated AEs in US pts with HER2- ABC and BRCA1/2mut.
METHODS: Oncologists retrospectively reviewed charts (July-Oct 2019) of randomly selected pts ≥18 y, with HER2- ABC and BRCA1/2mut (i.e., gBRCA1/2mut, somatic [sBRCA1/2mut], or sBRCA1/2mut with an unknown gBRCA1/2 status) who received ≥1 cytotoxic CT regimen(s) for ABC between Jan 2013–April 2018. AEs between different regimens were compared using χ2 or Fisher’s Exact test.
RESULTS: 203 pts were included: 99.5% were female and 76.4% were white. Median age was 58.0 y. 87.2% had gBRCA1/2mut, 8.4% had sBRCA1/2mut, and 4.4% had sBRCA1/2mut and unknown gBRCA1/2 status. 62.6% had advanced triple negative BC (TNBC), and 37.4% had hormone receptor (HR)+/HER2– ABC. In TNBC pts (n=127), 1st line therapies included non-platinum-based CT (58.3%) and platinum-based CT (41.7%). Hematologic AE’s occurred at higher rates in TNBC pts receiving platinum-based CT vs non-platinum-based CT (anemia, 41.5% vs 17.8%, P< 0.01; neutropenia, 22.6% vs 9.6%, P=0.04; thrombocytopenia, 22.6% vs 11.0%, P=0.08). In HR+/HER2- pts (n=76), CT (73.7%) or EBT (25.0%) were the most common 1st line therapies. Hematologic AE’s were reported in more pts receiving CT vs EBT (anemia, 28.6% vs 0.0%, P=0.01; neutropenia, 12.5% vs 5.3%, P=0.67; thrombocytopenia, 12.5% vs 5.3%, P=0.67).
CONCLUSIONS: In this analysis of HER2- BRCA1/2mut ABC pts, CT was most frequently used in the 1st line setting. Pts with advanced TNBC and BRCA1/2mut had more hematologic AEs reported in those receiving platinum-based CT vs non-platinum-based CT. Pts with HR+/HER2- ABC and BRCA1/2mut, as expected, had more hematologic AE’s in those receiving CT than those treated with EBT. Consideration of a regimen’s toxicity profile may help guide pts and providers in selection of their therapy regimen, including targeted treatments such as the newly approved BRCA1/2-targeted therapies, PARPi.
