In a nutshell
This study compared the safety and effectiveness of neratinib (Nerlynx) plus capecitabine (Xeloda) versus lapatinib (Tykerb) plus capecitabine in patients with human epidermal growth factor (HER2)-positive breast cancer (BC) spread (metastases) to the central nervous system (CNS; brain and spinal cord). The data showed that the neratinib plus capecitabine combination significantly improved survival without cancer worsening and CNS outcomes for these patients.
Some background
Breast cancer (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 is a protein that promotes the growth of some BCs. This subtype of BC is called HER2-positive (HER2+) BC. In 30-55% of the patients with metastatic HER2+ BC, cancer spreads to the CNS. Patients with HER2+ BC commonly receive targeted therapy such as lapatinib, tucatinib (Tukysa), and trastuzumab (Herceptin). These block HER2 and stops BC growth.
Capecitabine is a chemotherapy drug used to treat BC that is often used in combination with HER2-targeted therapies. Lapatinib plus capecitabine has been approved for HER2+ metastatic BC in patients who have received previous trastuzumab treatment. Neratinib is also a targeted therapy that showed effectiveness in preventing CNS metastases for patients with HER2+ BC. Neratinib plus capecitabine has shown effectiveness in treating patients with early-stage and advanced/metastatic HER2+ BC. However, the safety and effectiveness of neratinib plus capecitabine in patients with HER2+ BC having CNS metastases remain under investigation.
Methods & findings
This study involved 101 patients with HER2+ BC and CNS metastases. Patients were randomly assigned to 2 groups. Group 1 included 51 patients who received neratinib plus capecitabine. Group 2 included 50 patients who received lapatinib plus capecitabine. They were followed-up for 24 months.
The average survival without cancer worsening was longer for group 1 (7.8 months) than for patients in group 2 (5.5 months). Patients who received neratinib had a 34% lower risk of cancer worsening compared to patients who received lapatinib. The average overall survival was 16.4 months for group 1 compared to 15.4 months for group 2.
43 out of 101 patients required interventions for CNS disease (radiotherapy, surgery, anti-cancer medications). After 1 year, 25.5% of group 1 patients required intervention compared to 36% for group 2. The frequency of CNS disease progression was 26.2% for group 1 versus 41.6% for group 2.
More patients in group 1 responded to treatment in the CNS (26.3%) compared to group 2 (15.4%). The response to neratinib lasted longer (8.3 months) compared to lapatinib (5.3 months).
The most common side effects of treatment were diarrhea, headache, and dizziness.
The bottom line
This study concluded that neratinib plus capecitabine significantly improved survival without cancer worsening and CNS outcomes compared with lapatinib plus capecitabine in patients with CNS metastases from HER2+ metastatic BC.
The fine print
This study was sponsored by Puma Biotechnology, the manufacturers of neratinib.
Published By :
The Oncologist
Date :
May 24, 2021
