Endocrine-Immune-Based Therapies Improved Responses in Chemo-Insensitive Patients With HR+/HER2– Breast Cancer

Switching to endocrine-immune-based therapy improved response rates in chemo-insensitive patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) breast cancer (BC), with outcomes varying significantly by tumor subtype, according to data from the FINEST trial (NCT04215003). The results provide more comprehensive data about characteristics of HR+ tumors to help guide appropriate neoadjuvant treatment approaches in this patient population.¹

Cancerous cells in breast tissue with estrogen receptors | Image Credit: © Sathaporn - stock.adobe.com

HR+/HER2– BC is the most common BC subtype, accounting for approximately 70% of all invasive BC diagnoses. Patients with HR+/HER2– BC often face variable, if not poorer prognoses, and an increased risk of recurrence. Neoadjuvant therapies are the recommended treatment approach; however, the significant challenge of identifying an appropriate initial strategy for chemotherapy (CT) or endocrine therapy (ET) remains.²

Emerging research and clinical trials focus on improving pathological complete response (pCR) in patients with HR+/HER2– BC. Achieving favorable pCR is less common in patients receiving CT, driving the need for use of alternative therapies. Some clinical trial data show that combination of targeted therapies with cytotoxic agents yield higher pCR rates in patients, suggesting the superior benefit of this treatment approach for patients with HR+/HER2– BC. In the FINEST trial, researchers aimed to determine whether switching to ET combined with immunotherapy and CDK4/6 inhibitors could improve the response rate of chemo-insensitive patients with median-high risk HR+/HER2- BC.²

The trial included 121 patients with newly diagnosed, untreated HR+/HER2- BC who received 2 cycles of nab-paclitaxel (Abraxane; Abraxis BioScience) and carboplatin (Paraplatin; Bristol-Myers Squibb) (nabPCb). They were divided into groups A, B, C, and D. Group A (n=76) consisted of chemo-sensitive patients who continued nabPCb for 4 more cycles. Patients in groups B (n=9), C (n=27), and D (n=9) were randomized 1:3:1 to receive a new CT for 4 cycles or endocrine-immune-based therapy (dalpiciclib [SHR 6390; Jiangsu Hengrui Medicine Co], letrozole [Femara; Novartis Pharmaceuticals Corporation] and adebrelimab [Ariely; Shanghai Shengdi Pharmaceutical Co, Ltd], with goserelin [Zoladex; AstraZeneca] if patients were premenopausal) for 4 cycles or to undergo surgery.²

The primary and secondary end points of the study were pCR and objective response rate (ORR), respectively. The data showed that 4.1% of the total trial population achieved pCR, all of whom were from group A. The ORR was 81.8% in the total cohort, with rates of 100%, 66.7%, 81.5%, and 0% in groups A, B, C, and D, respectively. The data suggests that endocrine-immune-based therapy improved ORR, but not pCR rates in chemo-insensitive patients.²

In an exploratory analysis of the data, the researchers found that patients with the SNF4 subtype were the most sensitive to nabPCb (pCR rate of 21.1% vs. 1.8% in group A), whereas patients in group C with the SNF2 subtype were more sensitive to endocrine-immune-based therapy (Miller-Payne grade 4-5, 45.5% vs 6.3%). This suggests that the SNF4 subtype of HR+/HER2- BC was more chemo-sensitive, whereas the SNF2 subtype might be more sensitive to immunotherapy.²

The trial outcomes provide further data that can be used to curate combined therapy regimens and personalize treatment for patients. Although the pCR rates remained limited, the improved ORR in chemo-insensitive patients highlights the potential of endocrine-immune-based therapies as an alternative for those unlikely to benefit from standard chemotherapy. By integrating subtype-specific insights, these results could pave the way for more personalized and effective neoadjuvant strategies, ultimately improving outcomes and quality of care for patients with HR+/HER2– BC.

REFERENCES

1. A clinical trial of breast cancer neo-adjuvant therapy based on molecular pathway in FUSCC. Updated June 6, 2024. Accessed January 24, 2025. https://clinicaltrials.gov/study/NCT04215003

2. Chen L, Wu W, Liang F, et al. A prospective, phase II, neoadjuvant study based on chemotherapy sensitivity in HR+/HER2- breast cancer-FINEST study. Cancer Communications. January 4, 2025. doi:10.1002/cac2.12649