Evaluating the effectiveness and safety of different anti-HER2 therapies in combination with chemotherapy for metastatic HER2-positive breast cancer.

This study evaluated the effectiveness and safety of different anti-HER2 therapies in combination with chemotherapy for the treatment of patients with metastatic HER2-positive breast cancer (BC). The data showed that THP (taxanes + trastuzumab + pertuzumab) was the best first-line treatment, while Trastuzumab emtansine (T-DM1; Kadcycla) and XHTuC (capecitabine + trastuzumab + tucatinib) were the best second-line treatments for metastatic HER2-positive BC.

BC is classified into different subtypes depending on the presence or absence of certain receptors (proteins found on the surface of the cancer cells). HER2 (human epidermal growth factor receptor 2) is a protein that promotes the growth of some BC. This subtype of BC is called HER2-positive (HER2+) BC. Patients with metastatic HER2+ BC that has spread to distant organs have limited treatment options. Trastuzumab (Herceptin) and pertuzumab (Perjeta) are targeted therapy drugs used to treat metastatic HER2+ BC. Trastuzumab locks onto HER2 and inhibits its actions. However, some patients become resistant and stop responding to trastuzumab treatment.

Trastuzumab emtansine (T-DM1) is a drug like trastuzumab used in patients with BC that have high levels of HER2. It has been shown to improve survival outcomes and delay disease progression compared to a combination of capecitabine (Xeloda) and lapatinib (Tyverb). Capecitabine is a chemotherapy drug used to treat BC.

Tucatinib (Tukysa) is a type of targeted therapy known as a tyrosine kinase inhibitor (TKI). It is a new drug that targets HER2 and stops the cells from growing and spreading. Tucatinib in combination with trastuzumab and capecitabine significantly improved survival outcomes in patients with advanced HER2+ BC. However, studies evaluating the effectiveness and safety of each therapy and identifying the best therapy for metastatic HER2+ BC are still unknown.

This study analyzed 26 studies involving patients with metastatic HER2+ BC.

For first-line treatment, 16 studies were included. The regimens analyzed were TL (lapatinib + taxanes), THP (taxanes + trastuzumab + pertuzumab), TBevH (bevacizumab + taxanes + trastuzumab), TXH (capecitabin + taxanes + trastuzumab), TH (taxanes + trastuzumab), H (trastuzumab alone), and T (taxanes alone).

For first-line treatment, patients who received THP (70.5%) had the highest probability to survive without cancer progression and had the best overall survival rate (91.7%) compared to other treatment regimens. THP also had the best objective response rate (ORR; partial or complete disappearance of cancer) of 84.1% compared to other treatment regimens.

For second- or later-line treatment 10 studies were included. The regimens analyzed were T-DM1, XH (capecitabin + trastuzumab), XL (capecitabin + lapatinib), XHTuC (capecitabine + trastuzumab + tucatinib), and X (capecitabin alone).

Patients who received T-DM1 had the highest probability (87.3%) to survive without cancer progression and had the best overall survival rate (81.0%) compared to other treatment regimens.  

Patients who received XHTuC had the second-highest probability (81.2%) to survive without cancer progression and had the best ORR (84.9%) compared to other treatment regimens.  

This study concluded that THP was still the best first-line treatment for metastatic HER2+ BC. T-DM1 and XHTuC were recommended for second-line treatments.

This study included a small number of locally advanced BC patients which could lead to a slight difference. Some studies of new anti-HER2 agents like pyrotinib were not included.