Merck Presents Results from Phase 3 KEYNOTE-522 Trial of Neoadjuvant Keytruda Therapy in Pre- and Post-Surgery Early Stage Triple-Negative Breast Cancer Patients

Merck presented interim data from the phase 3 KEYNOTE-522 trial in patients with early-stage triple-negative breast cancer at the European Society for Medical Oncology (ESMO) 2019 Congress. The trial investigated a regimen of neoadjuvant Keytruda plus chemotherapy, followed by adjuvant Keytruda as monotherapy compared with a regimen of neoadjuvant chemotherapy followed by adjuvant placebo. The data are from the first randomized trial of anti-PD-1 therapy in the neoadjuvant/adjuvant setting for triple-negative breast cancer.

KEYNOTE-522 was a randomized, double-blind trial and enrolled 1,174 patients who were randomized 2:1 to receive either: 

  • The Keytruda regimen: Keytruda (Q3W) plus paclitaxel (weekly) and carboplatin (weekly or Q3W) for four cycles, followed by Keytruda plus cyclophosphamide and either doxorubicin or epirubicin (Q3W) for four cycles as neoadjuvant therapy prior to surgery, followed by nine cycles of Keytruda (Q3W) as adjuvant monotherapy post-surgery (n=784) or; 
  • The chemotherapy-placebo regimen: Placebo (Q3W) plus paclitaxel (weekly) and carboplatin (weekly or Q3W) for four cycles, followed by placebo plus cyclophosphamide and either doxorubicin or epirubicin (Q3W) for four cycles, followed by nine cycles of placebo (Q3W) as adjuvant therapy post-surgery (n=390). 

The dual primary endpoints were a pathological complete response (pCR) and event-free-survival (EFS). In the neoadjuvant phase, Keytruda plus chemotherapy (n=401) resulted in a statistically significant increase in pathological complete response (pCR) versus chemotherapy (n=201), from 51.2% with neoadjuvant chemotherapy to 64.8% for neoadjuvant Keytruda plus chemotherapy, in patients with early-stage TNBC. The improvement seen when adding Keytruda to neoadjuvant chemotherapy was observed regardless of PD-L1 expression. In the other dual primary endpoint of event-free-survival (EFS), with a median follow-up of 15.5 months, the Keytruda regimen reduced the risk of progression in the neoadjuvant phase and recurrence in the adjuvant phase by 37% – a favorable trend for EFS – compared with the chemotherapy-placebo regimen. 

Keytruda plus chemotherapy has been granted Breakthrough Therapy designation by the U.S. DA for the neoadjuvant treatment of patients with high-risk, early-stage TNBC.

About Triple-Negative Breast Cancer (TNBC) 

TNBC is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. As a result, TNBC does not respond to therapies targeting these markers, making it more difficult to treat. Approximately 15-20% of patients with breast cancer are diagnosed with TNBC. 

About Keytruda (pembrolizumab) Injection, 100 mg 

Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.