Background: In the CREATE-X trial, addition of adjuvant capecitabine after standard of care neoadjuvant chemotherapy improved clinical benefit in patients (pts) with early-stage triple-negative breast cancer (TNBC). The effect of adjuvant capecitabine in pts with BRCA1/BRCA2 mutation (BRCAm) has not been specifically examined, although some studies showed decreased benefit in pts with basal-like tumors, which are enriched in BRCA1m breast cancers. This study explored the effect of adjuvant capecitabine in a realworld cohort of pts with HER2-negative (HER2?) early breast cancer (eBC), stratified by BRCAm status and tumor subtype (hormone receptor positive [HR+]/HER2? or TNBC).
Methods: This retrospective study included de-identified data from US pts aged ?18 years in the Tempus real-world database who received adjuvant capecitabine for HER2? eBC between 1 Jan 2016 and 11?Nov 2022 and had known BRCA test results (BRCAm or nonBRCAm by germline, somatic, and/or tumor tissue testing). Pts who received neoadjuvant capecitabine 90 days from diagnosis, or adjuvant CDK4/6 inhibitor, PARP inhibitor, or immunotherapy were excluded. Demographics, clinical characteristics, and treatment patterns were described. Invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) were estimated using a Kaplan-Meier approach after the first breast surgery with curative intent.
Results: In total, 269 pts receiving adjuvant capecitabine with known BRCAm status were followed for a median of 23 months. Most pts had TNBC (n=192; 71.4%); 71 (26.4%) had HR+/HER2? eBC, and 6 had unknown subtype. BRCAm was reported in 22/269 (8.2%) pts (TNBC n=15/192, 7.8%; HR+/HER2? n=7/71, 9.9%). Median age at eBC diagnosis was 53 (range 2077) years, and was lower among pts with BRCAm (44 [2970] years) versus non-BRCAm (54 [2077] years). Most pts (n=245, 91.1%) had received ?1 neoadjuvant treatment (n=232, 86.2% received only chemotherapy) for a median of 133 (interquartile range [IQR] 105148) days. The median duration of adjuvant therapy was 168 (IQR 126210) days and most pts (n=219, 81.4%) had received adjuvant capecitabine monotherapy. Median IDFS (95% confidence interval [CI]) was 14.1 (10.7not estimable [NE]) months in pts with BRCAm and 16.9 (15.120.8) months in pts with non-BRCAm. At 6, 12, and 18 months respectively, IDFS (95% CI) rates were 95% (7299%), 55% (3274%), and 40% (1960%) for pts with BRCAm, and 96% (9398%), 69% (6274%), and 48% (4054%) for pts with non-BRCAm. Median IDFS (95% CI) was 21.2 (15.829.8) and 15.6 (12.817.8) months for pts with HR+/HER2? eBC and TNBC, respectively. At 6, 12, and 18 months respectively, IDFS (95% CI) rates were 98% (90100%), 77% (6486%), and 59% (4571%) for pts with HR+/HER2? eBC, and 95% (9197%), 64% (5671%), and 41% (3349%) for pts with TNBC. Median DDFS (95% CI) was 14.6 (10.7NE) and 19.1 (16.422.6) months in pts with BRCAm and non-BRCAm, respectively. At 6, 12, and 18 months respectively, DDFS (95% CI) rates were 100% (NE), 60% (3678%), and 40% (1960%) for pts with BRCAm, and 98% (9599%), 73% (6678%), and 52% (4459%) for pts with non-BRCAm. Median DDFS (95% CI) was 22.4 (16.229.8) and 16.9 (14.920.8) months in pts with HR+/HER2? eBC and TNBC, respectively. At 6, 12, and 18 months respectively, DDFS (95% CI) rates were 100% (NE), 79% (6587%), and 61% (4773%) for pts with HR+ eBC, and 97% (9399%), 69% (6276%), and 46% (3854%) for pts with TNBC.
Conclusions: In this real-world study of pts with known BRCAm status who received adjuvant capecitabine for HER2? eBC, there was a trend for shorter IDFS and DDFS in pts with BRCAm versus non-BRCAm. However, these results are descriptive, unadjusted, and limited by the small number of pts with BRCAm. Further investigation in a larger cohort of pts is warranted, considering that targeted therapeutic options exist for pts with BRCAm.
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