25 Treatment Patterns and Clinical Outcomes Following Endocrine Resistance Among HER2-Low Metastatic Breast Cancer Patients— Retrospective Observational Study

25 Treatment Patterns and Clinical Outcomes Following Endocrine Resistance Among HER2-Low Metastatic Breast Cancer Patients— Retrospective Observational Study

Background

Endocrine therapy (ET) with or without CDK4/6 inhibitors serves as an initial treatment for hormone receptor–positive/HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization–negative [ISH]–) metastatic breast cancer (mBC). However, many patients progress on ET-based regimens and receive subsequent chemotherapy (CT). This study examined treatment patterns and outcomes of patients with HR+/HER2-low mBC in US community oncology practices after developing endocrine resistance.

Methods

Oncologists from Cardinal Health’s Oncology Provider Extended Network provided data from medical charts of adult patients with HR+/HER2-low mBC who received at least 2 lines (2L) of systemic therapy, with the first line (1L) initiated between February 19, 2016, and December 31, 2018. Patients who received CT after progression on their last observed line of ET-based regimen were analyzed. Patient characteristics and treatment history were described, and Kaplan-Meier analyses of treatment outcomes including physician-reported real-world progression-free survival (rwPFS), time to treatment response (TTR), and time to treatment discontinuation (TTD) were performed.

Results

Included were 150 patients with HR+/HER2-low mBC [mean age, 61±11 years; 57.3% White; 32.7% African American] who had CT after ET resistance. The proportion of patients who stopped ET after 1L, 2L, and ≥3L of ET were 23.3% (n = 35), 70.7% (n = 106) and 6.0% (n = 9), respectively. The mean (SD) duration of ET-based regimens was 29.7 (13.12) months. Among patients who stopped ET after 1L (n = 35), most patients received fulvestrant plus palbociclib (48.6%) in 1L. Among those who stopped ET after ≥2L (n = 115), most patients received letrozole plus palbociclib (57.4%) in 1L and fulvestrant (46.1%) in 2L. The most common CT utilized was capecitabine (47.0%) followed by paclitaxel (28.0%).

The median rwPFS on CT was 8.12 months (95% CI, 7.36-9.24), with slightly shorter median rwPFS among those who stopped ET after 1L at 7.82 months (95% CI, 7.07-9.53) vs 8.19 months (95% CI, 6.97-9.99) in 2L. The median TTD of CT was 7.82 months (95% CI, 7.07-8.61) and TTR was 4.96 months (95% CI, 4.24-5.72), with similar estimates observed between patients who stopped ET after 1L and 2L+.

Conclusion

In this small sample of patients with HR+/HER2-low mBC, most patients switched to CT after 2L of ET-based regimens. Following ET resistance, durability of CT response was short and similar irrespective of number of prior lines of ET-based regimens. The findings highlight the unmet need for a more effective therapeutic alternative to CT after ET for patients with HR+/HER2-low mBC.