Evaluating the effectiveness of adding immunotherapy to chemotherapy for metastatic triple-negative breast cancer.

This study compared the effectiveness of adding immunotherapy (IT) to chemotherapy (CT) for the treatment of patients with metastatic triple-negative breast cancer (TNBC). The data showed that the addition of IT to CT significantly improved survival without cancer worsening. However, IT plus CT combination did not significantly improve overall survival and was associated with a higher rate of side effects 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, CT, and radiotherapy.

IT is a newer type of treatment that uses the body’s own system to fight cancer. Tumor cells try to avoid death by switching off our immune system. They bind to proteins on the surface of the immune cells such as PD-1/PD-L1. These proteins can stop the immune system from killing cancerous cells. Pembrolizumab (Keytruda) and nivolumab (Opdivo) are examples of PD-1 and PD-L1 inhibitors that work by inhibiting (blocking) PD-1/PD-L1. This inhibition triggers the immune system to attack tumor cells and kills them. Studies evaluating the effectiveness and safety of adding IT to CT for the treatment of patients with metastatic TNBC have shown different results. It is important to establish if the combination of IT and CT has real benefits for the treatment of patients with TNBC.

This study analyzed 4 studies that involved 3007 patients with mTNBC. Overall, 1028 patients had tumors that tested positive for the PD-L1 protein. 989 patients received PD-L1 inhibitors plus CT. 556 patients received PD-1 inhibitors plus CT. The rest of the patients received CT alone. 

In patients with tumor cells positive for PD-L1, PD-1/PD-L1 inhibitors plus CT significantly improved the survival without cancer worsening by 31% compared to CT alone. In all patients, PD-1/PD-L1 inhibitors plus CT significantly improved the survival without cancer worsening by 18% compared to CT alone.

However, the addition of PD-1/PD-L1 inhibitors to CT did not significantly improve the overall survival compared to CT alone, in both PD-L1 positive and negative patients.

IT plus CT was associated with 2.33 times more risk of side effects compared with CT alone.

This study concluded that the addition of CT to CT significantly improved survival without cancer worsening in patients with metastatic TNBC. However, this combination did not significantly improve overall survival and was associated with a higher rate of side effects in these patients.

This study looked back in time at medical records. Different studies analyzed in this study used different methods for PD-L1 testing. More studies are needed to validate the conclusions.