New findings from the CheckMate 7FL trial (NCT04109066) demonstrate a correlation between higher programmed death cell ligand 1 (PD-L1) expression and improved pathological complete response (pCR) and residual cancer burden (RCB) 0-1 rates in patients with high-risk, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. These results were presented at the 2023 San Antonio Breast Cancer Symposium (SABCS).
This phase 3 trial investigated the addition of nivolumab (Opdivo) to neoadjuvant chemotherapy and adjuvant endocrine therapy. Patients were randomized to receive either neoadjuvant chemotherapy plus nivolumab (360 mg every 3 weeks/240 mg every 2 weeks) or neoadjuvant chemotherapy plus placebo.
Diagram illustrating the two arms of the CheckMate 7FL trial: Arm A with nivolumab and Arm B with placebo. Image Credit: © SciePro – stock.adobe.com
Study Design and Patient Population
The CheckMate 7FL trial enrolled 521 newly diagnosed patients who were randomized 1:1 to receive either the nivolumab regimen (Arm A) or placebo (Arm B) in conjunction with neoadjuvant chemotherapy. Of these, 517 received treatment. The primary efficacy population (n=510) excluded 11 patients from Russian sites due to insufficient follow-up. PD-L1 expression was assessed using the SP142 and 28-8 combined positive score (CPS) assays in 510 and 349 patients, respectively. PD-L1 positivity was comparable between both arms.
Graph depicting PD-L1 expression levels in patients enrolled in the CheckMate 7FL trial. Image Credit: Pharmacy Times
Impact of Nivolumab on pCR and RCB
The study revealed that the addition of nivolumab significantly improved outcomes in patients with higher PD-L1 expression. The unweighted pCR rate was 16.6% for patients with CPS ≥1, 32.4% for CPS ≥10, and 52.3% for CPS ≥20. This contrasts with a pCR rate of 10.7% in the modified intention-to-treat (ITT) population and 5.7% in those with CPS <1.
Similar trends were observed for RCB 0-1 rates. The unweighted rate differences between the nivolumab and placebo arms were 17% for CPS ≥1, 34.4% for CPS ≥10, and 52.3% for CPS ≥20. In the modified ITT population, the RCB 0-1 rate was 9.4%, dropping to 3.3% in patients with CPS <1.
Additional Biomarker Analysis
Presenter Shirene Loi, MD, PhD, highlighted that nivolumab’s benefit was most pronounced in patients with tumor-infiltrating lymphocytes (TIL) expression ≥5%, ER expression ≤50%, and/or progesterone receptor expression ≤10% in patients with ER ≥10%. Increased pCR was noted with any TIL expression >1%. No association was observed between nivolumab benefit and Ki67.
Clinical Implications and Future Directions
During the discussion, Dr. Loi suggested that patients with ER >8-10% and those with minimal or no TIL expression may not benefit from nivolumab based on the CheckMate 7FL results. Ongoing exploratory analyses aim to further refine the patient subpopulation most likely to benefit from the addition of nivolumab to neoadjuvant chemotherapy in this high-risk breast cancer group.
Conclusion
The CheckMate 7FL trial provides valuable insights into the role of nivolumab in treating high-risk ER-positive, HER2-negative breast cancer. The findings suggest that PD-L1 expression, TIL levels, and ER/progesterone receptor expression may help identify patients who are most likely to benefit from this treatment strategy. For personalized treatment plans, consult with a healthcare professional today.
References
Loi S. Biomarker results in high-risk ER-positive, HER2-negative primary breast cancer following neoadjuvant chemotherapy with or without nivolumab: exploratory analysis of CheckMate 7 FL. Presented at: San Antonio Breast Cancer Symposium. December 5-9, 2023.
