Treatment patterns and clinical outcomes in HER2-low metastatic breast cancer, 2018–2023: A retrospective observational study.
Authors: Mayer Erica L. , Collin Simon M. , Hillman Sam , Berrocal-Almanza Luis C. , Sparano Joseph A. , Lam Clara 
Published: September 2024

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Background:
Current treatment options for patients (pts) with hormone receptor–positive (HR+) human epidermal growth factor receptor 2–low (HER2-low) (immunohistochemistry [IHC] 1+, IHC 2+/in situ hybridization–negative) metastatic breast cancer (mBC) who progress after endocrine therapy (ET) with or without targeted therapy, including CDK4/6 inhibitors (CDK4/6i) or inhibitors of the PIK3CA/AKT/mTOR pathway, have been limited to chemotherapy (CT).In this study, we assessed recent treatment patterns and clinical outcomes in US pts with HR+/HER2-low mBC.
Methods:
This was a retrospective observational study using the nationwide Flatiron Health electronic health record-derived de-identified database. Pts aged ≥18 years with no prior cancer (excluding non-melanoma skin cancer), de-novo or recurrent HR+/HER2-low mBC diagnosed between January 2018 and December 2022, and who received any line of treatment (LOT) for mBC (excluding clinical trials) were included. Demographic and clinical characteristics were captured prior to and at the index date (date of mBC diagnosis). Pts were followed up from index date to death, last activity date, or end of the study (September 30, 2023). Real-world overall survival (rwOS) from mBC diagnosis and real-world progression-free survival (rwPFS) from the start of each LOT was calculated using the Kaplan-Meier method.
Results:
A total of 2692 pts were eligible. Median follow up from mBC diagnosis was 38.3 months (interquartile range [IQR] 24.4, 53.4) and median age at mBC diagnosis was 65.0 years (IQR 56.0, 73.0); 45.3% of pts had de-novo mBC. Median LOT was 2.0 (IQR 1.0, 3.0) up to the end of the study (55.1% of pts received second-line [2L], 28.9% third-line [3L], 15.2% fourth-line [4L], and 7.2% fifth-line [5L] therapy). Serial ET cycles accounted for 65.7% of 2L, 45.2% of 3L, 27.9% of 4L, and 18.5% of 5L therapy. The most common drug categories by LOT are shown in the Table. Median rwOS was 43.0 months (95% confidence interval [CI] 40.0, 46.0). rwPFS was 20.5 months (95% CI 19.0, 22.3) in first-line [1L] therapy, 15.6 months (95% CI 14.0, 18.9) in 2L, 17.1 months (95% CI 13.5, 22.8) in 3L, and 13.4 months (95% CI 9.9, not estimable) in 4L.
Conclusions:
Treatment of HR+/HER2-low mBC has been heterogenous by LOT and mainly characterized by initial use of ET-based therapy followed by higher CT use in later lines. This is associated with diminishing effectiveness, highlighting a need for new treatments.

Top five drug categories by LOT, n (%).

1L (n=2692)
2L (n=1484)
3L (n=778)
4L (n=408)
5L (n=195)

ET + CDK4/6i
1537 (57.1)
694 (46.8)
217 (27.9)
76 (18.6)
25 (12.8)

Endocrine monotherapy
684 (25.4)
202 (13.6)
126 (16.2)
52 (12.8)
21 (10.8)

ET + mTORi
9*
61 (4.1)
55 (7.1)
25 (6.1)
17 (8.7)

ET + CT
50 (1.9)
74 (5.0)
45 (5.8)
29 (7.1)
22 (11.3)

CT alone
269 (10.0)
270 (18.2)
210 (27.0)
161 (39.5)
82 (42.1)

CDK4/6i alone
69 (2.6)
29*
8*
3*
3*

*Not a top five drug category in the specified LOT.