Pembrolizumab plus chemotherapy can delay progression of advanced triple negative breast cancer

This study investigated the effectiveness and safety of pembrolizumab (Keytruda) plus chemotherapy in patients with inoperable or metastatic triple-negative breast cancer. The data showed that the combination is effective in improving progression-free survival in these patients.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that tests negative for female hormone receptors (estrogen and/or progesterone) and the HER2 protein. TNBC accounts for 10-15% of all BCs. It is associated with a poorer disease outcome compared to other subtypes of BC. Treatments for TNBC usually involve a combination of surgery, chemotherapy, and radiotherapy.

Some cancer cells have on their surface proteins such as PD-L1 that binds to PD-1 protein which helps them avoid detection from the immune system. Pembrolizumab is an immunotherapy that helps the immune system detect and find cancer cells. It blocks the PD-1 protein. Pembrolizumab has been approved for use as a first-line treatment in metastatic TNBC. However, the effectiveness and safety of chemotherapy in combination with pembrolizumab in patients with metastatic TNBC have not been investigated.

This study involved 847 patients with inoperable or metastatic (spread) TNBC. Patients were randomly assigned to receive either pembrolizumab plus chemotherapy (566) or placebo plus chemotherapy. (281). The average follow-up period was 25.9-26.3 months.

Tumor samples were tested for the presence of PD-L1 protein on cancer cells and for the number of cells positive for PD-L1. A combined positive score (CPS) was calculated by dividing the number of PD-L1-positive cells to the total number of tumor cells multiplied by 100. 25% of all patients had a CPS less than 1 and 75% had a CPS of 1 or more. 38% of patients had a CPS of 10 or more.

Adding pembrolizumab to chemotherapy significantly improved survival without cancer progression in patients with a CPS of 10 or more (by 35%). It also slightly improved survival without cancer progression in those with a CPS of 1 or more (by 26%) compared to chemotherapy alone.

In patients with a CPS of 10 or more, 39.1% of the pembrolizumab group and 23% of the placebo group were alive after 12 months without cancer progression. In those with a CPS of 1 or more, 31.7% of the pembrolizumab group and 19.4% of the placebo group were alive after 12 months without cancer progression.

There was no difference in survival without cancer progression in patients with a CPS lower than 1.

Overall, a similar number of patients in both groups experienced side effects. Patients who received pembrolizumab had a higher occurrence of immune-related side effects than those who received placebo (26% vs 6%). The most common immune-related side effect was skin reactions. 

The investigators concluded that the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic TNBC significantly improves the outcomes of patients with a CPS of 10 or higher. 

This study was sponsored by Merck, Sharp & Dohme, the manufacturers of pembrolizumab.