March 31, 2025
3 min read
The addition of nivolumab to neoadjuvant chemotherapy significantly increased pathologic complete response among certain patients with breast cancer, according to findings published in Nature Medicine.
The randomized phase 3 CheckMate 7FL trial included 510 patients with high-risk, early-stage ER-positive, HER2-negative breast cancer.
Researchers randomly assigned them to receive anthracycline- and taxane-based neoadjuvant chemotherapy plus either IV nivolumab (Opdivo, Bristol Myers Squibb) or placebo.
Results showed a significantly higher pathologic complete response (pCR) rate — the study’s primary endpoint — in the nivolumab group (24.5% vs. 13.8%; P =.0021), with greater benefit derived by patients with PD-L1 expression of 1% or greater than those with lower or no PD-L1 expression (44.3% vs. 20.2%).
“The promising results of the CheckMate 7FL trial highlight the potential of expanding immunotherapy applications beyond traditionally considered immunogenic cancers,” Sherene Loi, MD, PhD, medical oncologist and clinician scientist at Peter MacCallum Cancer Centre in Australia, told Healio. “These findings underscore the importance of continued research and clinical trials to explore innovative treatment combinations, aiming to improve outcomes for a broader range of patients with breast cancer.”
Healio spoke with Loi about the motivation for this study, her reaction to the findings and the potential role this regimen may have in practice.
Healio: Prior to your study, what evidence existed about the potential role of neoadjuvant immunotherapy for high-risk breast cancer?
Loi: Before the CheckMate 7FL study, neoadjuvant chemoimmunotherapy had shown promise primarily in triple-negative breast cancer (TNBC). Clinical trials demonstrated that adding immunotherapy that targets PD-1 pathways — such as pembrolizumab (Keytruda, Merck) — to standard neoadjuvant chemotherapy improved pCR rates and EFS among patients with high-risk, early-stage TNBC. However, the efficacy of neoadjuvant chemo-immunotherapy in ER+/HER2-negative breast cancer — which accounts for a significant proportion of breast cancer cases — remained uncertain. This subtype traditionally was considered less immunogenic, leading to limited exploration of immunotherapeutic approaches for these patients.
Healio: What motivated you to study this?
Loi: The motivation for the CheckMate 7FL study stemmed from the need to improve outcomes for patients with high-risk ER-positive/HER2-negative breast cancer. Given the success of immunotherapy in other breast cancer subtypes, particularly TNBC, we hypothesized that combining immunotherapy with neoadjuvant chemotherapy could enhance treatment responses in a subset of ER-positive/HER2-negative patients, as well. High-grade ER-positive/HER2-negative cancers also have high quantities of immune infiltration, supporting the rationale for this trial.
The study aimed to evaluate whether adding nivolumab to standard chemotherapy could increase pCR rates, potentially leading to better long-term outcomes for this patient population.
Healio: Can you elaborate on the findings?
Loi: Adding nivolumab to neoadjuvant chemotherapy nearly doubled the number of patients who achieved pCR. This outcome suggests that incorporating nivolumab into treatment can enhance the likelihood of eradicating detectable cancer cells before surgery in this patient group. A subset of the trial patients who had evidence of immune cells in their tumors responded very well to the addition of nivolumab, resulting in unprecedented pCR rates never before seen in ER-positive/HER2-negative breast cancer.
Healio: What are the potential implications of this research?
Loi: The long-term implications could include establishing a new standard of care for patients with high-risk ER-positive/HER2-negative breast cancer by incorporating neoadjuvant immunotherapy into chemotherapy protocols. Improved pCR rates often are associated with better long-term outcomes, such as reduced recurrence rates and increased survival. If these benefits are confirmed with extended follow-up, this approach could lead to more effective treatment strategies and improved prognoses for this patient population. The KEYNOTE 756 study, which showed similar findings with an identical study design, supports the role of T cell immunosurveillance in high-grade ER-positive/HER2-negative breast cancer.
Importantly, it is plausible to hypothesize that these patients will not require extended durations of adjuvant endocrine therapy.
Healio: What are the next steps in research?
Loi: Future work will involve long-term follow-up of CheckMate 7FL study participants to assess whether the improved pCR rates translate into enhanced EFS and OS. Additionally, we plan to investigate other biomarkers that may predict which patients are most likely to benefit from neoadjuvant immunotherapy. Understanding the tumor microenvironment and immune landscape in ER-positive, HER2-negative breast cancer could help tailor treatments to individual patients, optimizing efficacy and minimizing unnecessary exposure to therapies.
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For more information:
Sherene Loi, MD, PhD, can be reached at sherene.loi@petermac.org.
Sources/Disclosures
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Healio Interviews
Disclosures:
Loi reports research funding to her institution from Adanate, Inc., Amaroq Therapeutics, AstraZeneca/Daiichi Sankyo, BioNTech, Bicycle Therapeutics, Bristol Myers Squibb, Domain Therapeutics, Eli Lilly & Co., Gilead Sciences, Menari-Asia Pacific, Mersana Therapeutics and SAGA Diagnostics.