Abstract PS11-42: Treatment patterns and clinical outcomes among patients (pts) with HER2- advanced breast cancer (ABC) and germline BRCA1/2 mutation(s) (gBRCA1/2mut): results from a US real-world study
Authors: Obeid Elias , Parikh Rohan C , Esterberg Elizabeth , Arondekar Bhakti , Hitchens Abigail , Arruda Lillian Shahied , Niyazov Alexander 
Published: February 2021

Background: gBRCA1/2mut represents~5% of ABC. Recently poly ADP-ribose polymerases inhibitors (PARPi) have demonstrated improved clinical outcomes, advantageous side effect profile, and favorable patient reported outcomes vs. chemotherapy(CT) in gBRCA1/2mut HER2- ABC patients. Optimal treatment sequencing has not been established. We assessed real-world treatment patterns and clinical outcomes by line of treatment (LOT) among adult patients with gBRCA1/2mut HER2- ABC.

Methods: US Oncologists retrospectively reviewed charts (July 2019-June 2020) of quasi-random selected patients ≥18 y, with gBRCA1/2mut HER2- ABC who received ≥1 cytotoxic chemotherapy (CT)regimen(s) for ABC between Jan 2013-April 2018. Descriptive analyses were performed for treatment patterns for the first 3 LOTs. Clinical outcomes (PFS by LOT and survival rates) were estimated using the Kaplan-Meier method. PARPi clinical outcomes data was immature given its recent launch. Additional analyses evaluating outcomes in patients receiving PARPi are planned.

Results: 305 HER2- gBRCA ABC patients were included: 99.7% were women, 76.4% were white, 11.5% were of Ashkenazi Jewish descent. Median age was 57.3 yrs, 36.4% had hormone receptor (HR)+/HER2-ABC, and 63.6% had advanced triple-negative BC (TNBC). Treatments for HR+/HER2-included: 1st line - CT (78.4%),endocrine based therapy (EBT) (19.8%), PARPi (0.9%), other (0.9%); 2ndline - EBT (51.2%), CT (31.0%), PARPi (13.1%),other (4.8%); 3rd line - CT (50.0%), EBT (27.8%), PARPi (19.4%). Across treatment types, 77.0% of patients were alive at 2 years after 1stCT. Treatment for TNBC included: 1st line - non-platinum based CT(60.8%), platinum based CT (39.2%), non-platinum based CT (60.8%); 2ndline - PARPi (42.0%), non-platinum based CT (40.2%), platinum-based CT (10.7%),other (7.1%); 3rd line - PARPi (43.5%), non-platinum based CT (39.1%), platinum-based CT (6.5%). Across treatment types, 73.9% of patients were alive at 2 years after 1stCT. Median PFS for HR+/HER2- and TNBC are reported in Table 1.

Conclusion: CT was frequently used among both HR+ and HR- gBRCA1/2mut HER2-ABC. Recent clinical trials have demonstrated use of chemotherapy-sparing disease specific targeted treatments (e.g., PARPi) improved clinical, and patient reported outcomes, and had a manageable side effect profile. Such disease specific targeted therapies should possibly be considered in earlier LOTs in this patient population and is an area that could benefit from well-designed studies, particularly addressing this important research question. Therefore, future studies assessing treatment sequencing and the associated clinical outcomes including targeted treatments (i.e. PARPi) in patients with gBRCA1/2mut are warranted. Funding: Pfizer

Table 1. PFS (months) by LOT and HR status among gBRCA1/2mut HER2- ABC patients.HR+/HER2-TNBC1st line (n)110190PFS, median no. (95% CI)12.1 (9.1-14.3)11.6 (9.9-13.6)2nd line (n)6864PFS, median no. (95% CI)14.2 (10.7-29.5)9.0 (6.2-11.4)3rd line (n)2926PFS, median no. (95% CI)6.5 (4.4-9.3)5.9 (3.5-not estimable)

Citation Format: Elias Obeid, Rohan C Parikh, Elizabeth Esterberg, Bhakti Arondekar, Abigail Hitchens, Lillian Shahied Arruda, Alexander Niyazov. Treatment patterns and clinical outcomes among patients (pts) with HER2- advanced breast cancer (ABC) and germline BRCA1/2 mutation(s) (gBRCA1/2mut): results from a US real-world study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-42.