Episode 21: Neoadjuvant immunotherapy for high-risk ER+/HER2- breast cancer: insights from the CheckMate-7FL trial

In this episode of WND Breast, Dr Kevin Punie from GZA Hospitals and Prof Evandro de Azambuja from Institut Jules Bordet will discuss the CheckMate-7FL study, which investigates the use of immune checkpoint inhibitors in the neoadjuvant setting for luminal disease.

This randomized, double-blind phase 3 trial focused on high-risk, ER+/HER2- primary breast cancer. Nivolumab and placebo were added to neoadjuvant chemotherapy, followed by adjuvant endocrine therapy with or without nivolumab for 1 year.

Newly diagnosed patients were selected based on clinical stage and biology, including stages T1c–2 N1–2 or T3–4 N0–2, with grade 2 (ER 1–10%) or grade 3 (ER ≥ 1%). The primary outcome, pCR, increased by approximately 9%.

Biomarker analysis revealed intriguing findings. PD-L1 positive disease correlated with increased benefit in the nivolumab group, exceeding 25% in patients with the strongest PD-L1 expression. Half of the patients lacked any TILs (<1%), showing no benefit. However, when TILs were present, there was a benefit, although a higher TILs score did not correlate with increased benefit. The Ki-67 proliferation index did not correlate with nivolumab response. The greatest benefit in pCR was observed in patients with low ER and positive PD-L1, with absolute increases over 30% by adding a checkpoint inhibitor.

These preliminary data demonstrate significant benefits but are not yet correlated with long-term clinical outcomes in this patient cohort.

Regarding safety, most adverse events were due to the chemotherapy backbone. A significant proportion of patients experienced immune-related adverse events, manageable without impacting QoL. However, in rare cases, immune-related adverse events can be dramatic, significantly affecting long-term QoL. Therefore, it’s crucial to determine how many relapses can be prevented, not just the increase in pCR.

The data from the CheckMate-7FL trial present intriguing preliminary results requiring further follow-up before being applicable in clinical practice.