Adding pembrolizumab before and after surgery for early triple-negative breast cancer

This study aimed to investigate pembrolizumab (Keytruda) before and after surgery in patients with early triple-negative breast cancer (TNBC). 

This study concluded that the addition of pembrolizumab to chemotherapy before surgery and after surgery for TNBC improved the survival without complications from TNBC in these patients. 

TNBC is cancer that does not grow in response to female sex hormones (estrogen and progesterone) or the HER2 protein. The main treatment for TNBC is surgery to remove the tumor. Neoadjuvant (NA) treatment such as chemotherapy or targeted therapy is commonly given as a first step to shrink a tumor before surgery. Adjuvant treatment can also be given after surgery to kill any cancer cells left after surgery. This helps reduce the risk of cancer coming back.  

Pembrolizumab is an immunotherapy that activates the immune system to kill cancer cells. Earlier studies have shown that adding pembrolizumab to NA chemotherapy has led to significantly more patients with early TNBC having a pathological complete response (defined as no invasive cancer in the breast and negative nodes after surgery). 

Event-free survival (EFS) is the length of time after primary treatment that the patient remains free of complications or events caused by the cancer. It was unknown whether the addition of pembrolizumab as NA and adjuvant treatment in patients with early TNBC improves the rate of EFS.  

This study involved 1174 patients with previously untreated stage II or III TNBC. Patients were randomly assigned to 2 groups. Group 1 included 784 patients that were treated with pembrolizumab and chemotherapy (PemChem) before surgery. Group 2 included 390 patients that were treated with placebo and chemotherapy (PlaChem) before surgery. After breast surgery, group 1 received 9 cycles of pembrolizumab every 3 weeks and group 2 received a placebo. Patients were followed up for an average of 39.1 months.   

The estimated EFS at 36 months was 84.5% for the PemChem group compared to 76.8% for the PlaChem group. Pembrolizumab therapy was associated with a 37% higher chance of a better EFS compared to placebo.

The cancer came back (recurrence) in 7.7% of patients in group 1 compared to 13.1% of patients in group 2. Pembrolizumab treatment was associated with a 39% lower risk of cancer progression, spread or death compared to placebo.  

Side effects occurred mostly during the NA phase of the treatment. Side effects realted to the treatment occurred in 77.1% of patients in group 1 and 73.3% of those in group 2. The most common side effects were nausea, anemia, and hair loss. 

This study concluded that the addition of pembrolizumab to chemotherapy as a neoadjuvant treatment and then after surgery in patients with early TNBC led to improved EFS rates.

This study was funded by Merck Sharp and Dohme, the manufacturer of pembrolizumab.