Pembrolizumab/Chemo Yields pCR Benefit in High-Risk ER+ HER2– Breast Cancer

Investigators of the double-blind randomized phase 3 KEYNOTE-756 trial are assessing pembrolizumab plus chemotherapy as a neoadjuvant regimen followed by adjuvant pembrolizumab plus endocrine therapy in patients with high-risk, early-stage, ER-positive, HER2-negative breast cancer.

Combining neoadjuvant pembrolizumab (Keytruda) with chemotherapy led to a statistically significant improvement in pathological complete response (pCR) vs neoadjuvant placebo plus chemotherapy in patients with high-risk, early-stage estrogen receptor (ER)–positive, HER2-negative breast cancer, according to a press release on findings from a prespecified interim analysis of the phase 3 KEYNOTE-756 trial (NCT03725059).

Investigators will continue to evaluate the study’s other primary end point of event-free survival (EFS) following a positive recommendation from the Data Monitoring Committee. Pembrolizumab’s safety profile was comparable with previous reports of the agent, and there were no new safety signals. Investigators plan to present their findings at a future medical meeting.

“Worldwide, more than 2 million people are diagnosed with breast cancer each year, and it is critically important that breast cancer is found and treated early, especially for patients with high-risk disease,” co-principal investigator Aditya Bardia, MD, MPH, said in the press release. “While we wait for [EFS] data, these initial pCR results provide a potentially encouraging signal and may have important therapeutic implications for patients with high-risk, early-stage, ER-positive, HER2-negative breast cancer.”

Bardia is an attending physician of medical oncology at Massachusetts General Hospital, director of Breast Cancer Research at Massachusetts General Cancer Center, and an associate professor at Harvard Medical School.

Investigators of the double-blind randomized phase 3 KEYNOTE-756 trial are assessing pembrolizumab plus chemotherapy as a neoadjuvant regimen followed by adjuvant pembrolizumab plus endocrine therapy in patients with high-risk, early-stage, ER-positive, HER2-negative breast cancer. A total of 1240 patients were randomly assigned to receive 200 mg of pembrolizumab or matched placebo every 3 weeks plus paclitaxel for 4 cycles followed by 4 additional cycles of pembrolizumab or placebo in combination with doxorubicin or epirubicin (Pharmorubicin) plus cyclophosphamide before surgery. Following surgery, patients then received 9 cycles of pembrolizumab or placebo once every 3 weeks plus endocrine therapy for up to 10 years.

Secondary end points include overall survival, adverse effects (AEs), serious AEs, treatment discontinuation due to AEs, and quality of life.

Patients 18 years and older with locally confirmed invasive breast ductal adenocarcinoma and centrally confirmed ER-positive, HER2-negative grade 3 breast cancer of ductal histology were eligible for enrollment on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1, and adequate organ function.

Those with a history of non-infectious pneumonitis requiring treatment with steroids or breast cancer with lobular histology were not able to enroll on the study. Patients were also unsuitable for enrollment if they had bilateral invasive breast cancer; stage IV breast cancer; ER-negative, progesterone receptor­–positive breast cancer; or an additional known malignancy that progressed or required active treatment within 5 years prior to study entry.

“While significant advancements have been made in the treatment of ER-positive, HER2-negative breast cancer, people diagnosed with high-risk disease as assessed by clinical and pathologic criteria typically have a worse prognosis and limited options before surgery. Data from [the] KEYNOTE-756 [trial] suggest that adding pembrolizumab to neoadjuvant chemotherapy before surgery can significantly improve the pCR rate compared to neoadjuvant chemotherapy alone for people with high-risk, early-stage ER-positive, HER2-negative breast cancer,” co-principal investigator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Centre in Lisbon, Portugal, concluded.

Reference

Merck announces phase 3 KEYNOTE-756 trial met primary endpoint of pathological complete response (pCR) rate in patients with high-risk, early-stage ER+/HER2- breast cancer. News release. Merck. July 28, 2023. Accessed July 28, 2023. https://shorturl.at/GIRZ1