ESMO 2023: LBA21
Keytruda (pembrolizumab) is a highly specific, human-made antibody that targets the PD-1 pathway and prevents cancer cells from escaping the immune system. It has been approved for treating early-stage TNBC with high risk of recurrence. In a Phase III study by Merck, KEYNOTE-756, a major breakthrough was achieved: a remarkable increase in the rate of pCR in patients with early-stage ER+/HER2– breast cancer with high risk. This improvement was seen in a planned interim analysis, showing that adding Keytruda to neoadjuvant chemotherapy was better than placebo plus chemotherapy. The safety profile of pembrolizumab was consistent with previous studies, with no new safety issues.
At the May 2023 cutoff, after a median follow-up of 33.2 months, a significant improvement in pCR was observed with pembrolizumab and chemotherapy compared to the placebo and chemotherapy group (24.3% vs. 15.6%) in the ITT population. The positive effect of pembrolizumab plus chemotherapy on pCR was similar 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 heart attack. EFS results are still being evaluated, but these results represent a major step forward in treating high-risk breast cancer. Specifically, pembrolizumab added to neoadjuvant chemotherapy has shown promising results, giving new hope to people with early-stage ER+/HER2– breast cancer.
Merck is exploring the potential of Keytruda in early stage cancer in a big way, with more than 25 ongoing studies covering a wide range of cancer types. This expansion builds on the proven success of Keytruda in advanced disease stages.
Keytruda is not just a drug, it’s a revolution in cancer treatment. It empowers the immune system to fight cancer cells and gives patients a chance to live longer and better lives. Keytruda is changing the game for early-stage breast cancer patients with high risk.
Conclusion
The KEYNOTE-756 trial has made a significant breakthrough in the treatment of high-risk, early-stage ER+/HER2– breast cancer, a group that previously had limited therapeutic options and faced less favorable outcomes before surgery. This Phase III immunotherapy study, featuring pembrolizumab alongside neoadjuvant chemotherapy, achieved its primary objectives and demonstrated a substantial 8.5 percentage point increase in the rate of complete pathological response (pCR) across the entire study population, regardless of PD-L1 status.
While EFS results are still under evaluation, the early success of incorporating pembrolizumab into the chemotherapy regimen is promising and offers new hope for patients with this specific form of breast cancer. This marks a significant advancement in the field, opening the door to more effective treatments for high-risk, early-stage ER+/HER2– breast cancer, ultimately improving patient outcomes and the quality of care in this challenging context.
