KEYTRUDA (pembrolizumab) is a highly selective, humanized monoclonal immunoglobulin G4κ antibody that blocks the PD-1 ligands PD-L1 and PD-L2 and has received approval for treating high-risk early-stage TNBC. In Merck's Phase III trial, KEYNOTE-756, a significant milestone has been reached with the achievement of the primary endpoint: a noteworthy increase in the rate of pCR in patients with high-risk early-stage ER+/HER2– breast cancer. This progress was observed during a predetermined interim analysis, showing the KEYTRUDA-based regimen to be superior to neoadjuvant placebo plus chemotherapy. Importantly, the safety profile of pembrolizumab remained consistent with prior studies, with no new safety concerns emerging. 

As of the May 2023 cutoff, a median follow-up of 33.2 months was noted, revealing a substantial improvement in pCR with pembrolizumab and chemotherapy compared to the placebo and chemotherapy group (24.3% vs. 15.6%) in the intent-to-treat (ITT) population. The positive impact of pembrolizumab combined with chemotherapy on pCR was consistent across predefined subgroups. In the neoadjuvant phase, grade ≥3 treatment-related AE rates were 52.5% with pembrolizumab + chemotherapy and 46.4% with pembrolizumab + chemotherapy, with 1 death in the pembrolizumab arm due to acute myocardial infarction. While EFS results are still under assessment, these findings represent a significant advancement in treating high-risk breast cancer. Specifically, adding pembrolizumab to neoadjuvant chemotherapy has shown promising results, offering new hope to individuals with high-risk early-stage ER+/HER2– breast cancer.

Merck is significantly expanding its exploration of KEYTRUDA's potential in early stage cancer, with a robust portfolio of over 25 ongoing registrational studies covering a wide spectrum of cancer types. This expansion capitalizes on the well-documented success of KEYTRUDA in advanced disease states. 

KOL insights

“All subgroups derive a benefit from pembrolizumab. Particularly, 55.9% of patients with ER-low disease who received pembrolizumab (n = 34) achieved a pCR vs 30.2% of those who had ER-low disease and received placebo (n = 43; ∆, 25.6; 3.3-45.8)”–MD, director of the Breast Unit at Champalimaud Clinical Center in Lisbon.

Conclusion

While there has been substantial advancement in ER+/HER2– breast cancer treatment, individuals with high-risk cases have had limited treatment options and less favorable outcomes before undergoing surgery. KEYNOTE-756 marks the first fully enrolled Phase III immunotherapy study for high-risk, early-stage ER+/HER2– breast cancer and successfully met its two primary objectives. The introduction of pembrolizumab alongside neoadjuvant chemotherapy resulted in a statistically significant 8.5 percentage point increase in the rate of complete pathological response (pCR) within the entire study population, regardless of PD-L1 status. The study is also designed to assess Event-Free Survival as one of its dual primary objectives, although EFS results are still in their early stages and are continuously under evaluation. The incorporation of pembrolizumab into the chemotherapy regimen has demonstrated a noteworthy rise in the achievement of pCR in patients with this specific form of breast cancer.

For more insight into the country-specific epidemiology, treatment pattern analysis, and changing market dynamics on early and metastatic breast cancer, refer to Early stage HR+/HER2- Breast Cancer Market Forecast and Metastatic HR+ HER2-negative Breast Cancer Market Insight and Forecast Report