OBJECTIVES: The phase III KEYNOTE-756 trial revealed that addition of pembrolizumab (versus placebo) to neoadjuvant chemotherapy followed by adjuvant pembrolizumab (versus placebo) and endocrine therapy, resulted in significantly improved pathological complete response rates among patients with early-stage, high-risk, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer. This study aimed to examine US oncologists' perceptions and application of these results.

METHODS: A survey to assess clinical practices regarding neoadjuvant therapy for early-stage high-risk, ER+/HER2– breast cancer and perceptions of KEYNOTE-756 was administered to US-based oncologists/hematologists attending two live meetings in February and March 2024. Aggregate responses were summarized using descriptive statistics.

RESULTS: Among respondents (N=98), 79% were community-based with an average of 20.6 years of clinical experience. Before reviewing KEYNOTE-756, nearly two-thirds of respondents reported preference for neoadjuvant chemotherapy for early-stage high-risk, ER+/HER2− breast cancer, with about one-quarter reporting its use in ≥40% of eligible patients. Respondents reported nodal involvement (54%) and stage of disease (45%) as top influential factors in neoadjuvant treatment selection.

After reviewing KEYNOTE-756, 96% of respondents anticipated they would incorporate neoadjuvant pembrolizumab plus chemotherapy for early-stage, high-risk, ER+/HER2– breast cancer patient subgroups including; positive lymph nodes, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1, and PD-L1 CPS ≥1 and ER-positivity<10%. Respondents reported top barriers to prescribing neoadjuvant immunotherapy included; limited long-term survival data (54%), cumbersome payer approval process (29%), and toxicity concerns (27%).

CONCLUSIONS: Overall, oncologists were receptive to adding immunotherapy to neoadjuvant chemotherapy for high risk, ER+/HER2- breast cancer after reviewing KEYNOTE-756 data. Ongoing investigation into survival data from KEYNOTE-756 holds promise for informing neoadjuvant treatment decisions and optimizing therapy selection in ER+/HER2– breast cancer. If approved by the FDA, this may provide a new standard of care for this patient population. Future real-world evidence may also play a crucial role in shaping clinical practice.