Abstract PS13-41: Real-world evidence of platinum-based chemotherapy for the treatment of BRCA-positive metastatic breast cancer in a cohort of 33,878 women in the United States
Authors: Wendy Sebby, Alexander Liede, Debasish Mazumder, Anirban Ghosh, Eros Papademetriou, Ravi Potluri, Bruce Bach, Jerzy Tyczynski
Journal: Cancer Research (2021)

Abstract Background The choice of chemotherapy for women diagnosed with metastatic breast cancer (BC) has been evolving as new agents and clinical trial results become available. Current NCCN guidelines recommend sequential single chemotherapeutic agents and combination therapy including platinum-based regimens for patients with high risk disease. Platinum-based chemotherapies are recommended for triple-negative breast cancer (TNBC) and, in particular, for a more defined population of TNBC with a BRCA mutation that may have particular sensitivity to platinum agents due to the impaired ability to repair DNA damage inherent in these patients.1 Here, we aim to leverage real world data to ascertain the use of platinum-based treatments in BRCA-mutation positive (BRCA+) metastatic BC patients, characterized by their hormonal receptor status. Methods Optum’s electronic health records (EHR) database was used to identify a cohort of women with 1) confirmed BC ICD-9/ICD-10 diagnosis between 2008 and 2018, 2) at least 12 months of history in the EHR, 3) at least one distant metastasis diagnosis (per ICD-9/ICD-10, or from physician notes), and 4) no previous diagnosis of other primary cancers in previous 12 months. BRCA-mutation status, ER, PR and HER2 test results were used to create relevant biomarker subgroups. Distinct lines of therapy (LOT) in the post-metastatic period were established using business rules, and the extent of use of platinum-based treatments, overall and of specific platinum regimens, were analyzed in various LOTs. Results Among 33,878 metastatic BC patients receiving a systemic chemotherapy, 8.7% were treated with a platinum-based regimen, while among the subgroup who were BRCA+, the proportion receiving platinum-based regimens was higher at 12.3%. In LOT2 and LOT3, the proportion receiving platinum regimens was 3.9% and 2.5% for the overall cohort, compared with 5.2% and 3.0% for the BRCA+ cohort. Within the BRCA+ cohort, the use of platinum-based regimens in TNBC patients was substantially higher than in other patients, accounting for 21.6%, 15.3% and 14.2% of patients in LOT1, LOT2 and LOT3 respectively, compared with 8.7%, 3.1% and 1.7% in ER+/PR+ patients (Table 1). The choice of specific platinum-containing combination regimens differed by biomarker cohorts; the combination of carboplatin and paclitaxel was most common in TNBC patients, while a quadruplet regimen was most used in the ER+/PR+ cohort. Conclusions Real-world evidence on use of platinum-based regimens in metastatic BC patients revealed differences across BRCA and hormonal status phenotypes. Women with TNBC had higher use of platinum agents than other subgroups across all lines of treatment. The observation that the use of platinum-based chemotherapy, including combination regimens, was highest in TNBC across lines of treatment highlights the persistent unmet need around alternative therapies for women affected with TNBC and BRCA+ disease. Table 1. Use of platinum-based regimens in women with metastatic BC in LOTs 1-3All metastatic BCBRCA+All BRCA+ER+/PR+TNBCN (treated with LOT1)33,8785,6494,228782Age at LOT1 start (in years): Median (IQR)63 (53-73)54 (46-64)54 (46-64)54 (45-62)Total proportion (%) of platinum-based regimens in LOT18.7%12.3%8.7%21.6%REGIMENCarboplatin+paclitaxel1.8%2.8%1.4%8.3%Carboplatin+docetaxel+pertuzumab+trastuzumab1.7%2.8%2.6%0.4%Carboplatin+docetaxel+trastuzumab1.2%1.9%1.8%0.3%Carboplatin+gemcitabine0.9%1.4%0.7%5.5%Carboplatin0.7%0.8%0.5%1.9%Carboplatin+docetaxel0.3%0.4%0.2%1.3%Cisplatin0.3%0.4%0.2%1.0%Other platinum-based regimens1.9%2.0%1.4%2.9%N (treated with LOT2)21,1484,1973,317495Total proportion (%) of platinum-based regimens in LOT23.9%5.2%3.1%15.3%N (treated with LOT3)13,9372,9592,523226Total proportion (%) of platinum-based regimens in LOT32.5%3.0%1.7%14.2%Footnotes1 Isakoff, SJ. Triple-Negative Breast Cancer: Role of Specific Chemotherapy Agents. Cancer J 2010;16: 53-61 Citation Format: Wendy Sebby, Alexander Liede, Debasish Mazumder, Anirban Ghosh, Eros Papademetriou, Ravi Potluri, Bruce Bach, Jerzy Tyczynski. Real-world evidence of platinum-based chemotherapy for the treatment of BRCA-positive metastatic breast cancer in a cohort of 33,878 women in the United States [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 PS13-41.