Neoadjuvant Pembrolizumab Plus Chemotherapy Improves pCR Rate in High-Risk, Early-Stage ER+/HER2– Breast Cancer

Neoadjuvant pembrolizumab (Keytruda) plus chemotherapy led to an improvement in pathological complete response (pCR) rate compared with chemotherapy plus placebo in patients with high-risk, early-stage, estrogen receptor (ER)–positive, HER2-negative breast cancer, meeting one of the dual primary end points of the phase 3 KEYNOTE-756 trial (NCT03725059) following the neoadjuvant portion of the study.¹

Findings from a prespecified interim analysis showed that patients in the pembrolizumab arm experienced a statistically significant improvement in pCR rate vs those given neoadjuvant placebo plus chemotherapy, per an independent data monitoring committee (IDMC).

The IDMC recommended the trial continue without changes to evaluate the other primary end point, event-free survival. Detailed results will be presented at an upcoming medical meeting.

“This is the first positive phase 3 study evaluating an immunotherapy-based regimen for patients with high-risk, early-stage, ER-positive, HER2-negative breast cancer, and an important milestone in our efforts to advance research in early-stage breast cancer,” Gursel Aktan, MD, vice president of Global Clinical Development at Merck Research Laboratories, stated in a news release. “We look forward to sharing the detailed results with the medical community and thank the patients and investigators for their important contributions to this study.”

KEYNOTE-756 was a randomized, double-blind trial that enrolled patients with centrally confirmed ER-positive/HER2-negative, grade 3 breast cancer.² Patients needed to have localized invasive breast ductal adenocarcinoma that was either T1c-T2 (tumor size ≥2 cm), cN1-cN2, or T3-T4, cN0-cN2. Patients with inflammatory breast cancer were allowed to enroll. Other key inclusion criteria included an ECOG performance status of 0 or 1 and adequate organ function.

Patients were excluded if they had a history of non-infectious pneumonitis that required treatment with steroids or current pneumonitis, breast cancer with lobular histology, bilateral invasive breast cancer, metastatic stage IV breast cancer, or multi-centric breast cancer.

The trial enrolled 1240 patients who were randomly assigned 1:1.¹ Patients in the experimental arm received 200 mg of pembrolizumab every 3 weeks plus 80 mg/m² of paclitaxel once per week for 4 21-day cycles, followed by 4 additional cycles of pembrolizumab plus 60 mg/m² of doxorubicin or 100 mg/m² of epirubicin plus 600mg/m² of cyclophosphamide once every 2 or 3 weeks as neoadjuvant therapy prior to surgery, followed by 9 cycles of pembrolizumab once every 3 weeks plus endocrine therapy for up to 10 years as adjuvant treatment. Those in the control arm were given the same chemotherapy regimens plus placebo in the neoadjuvant setting, followed by 9 cycles of placebo plus up to 10 years of endocrine therapy in the adjuvant setting.^1,2

Secondary end points included overall survival and safety.

Regarding safety, findings for pembrolizumab were consistent with previously reported data from past trials, and no new safety signals were identified.¹

References

1. 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://www.merck.com/news/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/
2. Study of pembrolizumab (MK-3475) versus placebo in combination with neoadjuvant chemotherapy & adjuvant endocrine therapy in the treatment of early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer (MK-3475-756/KEYNOTE-756). ClinicalTrials.gov. Updated July 28, 2022. Accessed July 28, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03725059