An international clinical trial led by researchers at the Peter MacCallum Cancer Centre in Melbourne has demonstrated a significant improvement in cure rates for the most common form of breast cancer (ER+/HER2-) through the addition of the immunotherapy drug nivolumab to standard chemotherapy.
The Phase III CheckMate-7FL trial, the results of which were published in Nature Medicine, involved 510 patients with newly diagnosed, early-stage, high-risk ER+/HER2- breast cancer. This subtype accounts for approximately 70% of all breast cancer cases globally. The study evaluated the impact of adding nivolumab to neoadjuvant chemotherapy, which is administered before surgery to shrink the tumor.
Key Findings of the CheckMate-7FL Trial
The trial's primary endpoint was the pathological complete response (pCR) rate, defined as the absence of detectable cancer cells in tissue samples after treatment. The results showed a statistically significant improvement in pCR rates among patients treated with nivolumab plus chemotherapy compared to those who received chemotherapy plus a placebo. Specifically, the pCR rate was 25% in the nivolumab group versus 14% in the placebo group.
Professor Sherene Loi, a medical oncologist from Peter Mac and the trial's lead investigator, stated, "These patients are considered to be likely cured because their tumor was removed and samples of breast and lymph node tissue collected at the same time also show no detectable cancer cells. The number of patients who achieved this pCR improved significantly as a result of nivolumab, an exciting result that points to a new treatment paradigm in this most common type of breast cancer."
Enhanced Response in PD-L1 Positive Tumors
Notably, a subgroup of patients with tumors expressing the PD-L1 biomarker exhibited an even more pronounced response to nivolumab. In this subgroup, the pCR rate was 44% in the nivolumab group compared to 20% in the placebo group. This suggests that PD-L1 expression may be a predictive biomarker for nivolumab response in ER+/HER2- breast cancer.
Safety and Tolerability
While the addition of nivolumab to chemotherapy was generally well-tolerated, there were some safety concerns. The most common adverse events (AEs) included alopecia, nausea, anemia, and fatigue, with similar rates across both treatment groups. However, serious AEs and treatment-related AEs leading to discontinuation were more frequently reported in the nivolumab group. There were five deaths in the nivolumab arm, two of which were related to drug toxicity, while no deaths occurred in the placebo arm.
Clinical Implications
The results of the CheckMate-7FL trial suggest that the addition of nivolumab to neoadjuvant chemotherapy may represent a new standard of care for patients with high-risk, early-stage ER+/HER2- breast cancer. The observed improvement in pCR rates, particularly in patients with PD-L1 positive tumors, highlights the potential of immunotherapy to enhance treatment outcomes in this common breast cancer subtype. Longer follow-up is needed to determine whether the improved pCR rates translate into improved event-free survival.
