Positive human epidermal growth factor receptor 2 (HER2) expression is associated with an increased risk of metastases especially those to the brain in patients with advanced breast cancer (BC). Neratinib as a tyrosine kinase inhibitor can prevent the transduction of HER1, HER2 and HER4 signaling pathways thus playing an anticancer effect. Moreover, neratinib has a certain efficacy to reverse drug resistance in patients with BC with previous HER2 monoclonal antibody or targeted drug resistance. Neratinib, as monotherapy and in combination with other therapies, has been tested in the neoadjuvant, adjuvant, and metastatic settings. Neratinib with high anticancer activity is indicated for the prolonged adjuvant treatment of HER2-positive early BC, or in combination with other drugs including trastuzumab, capecitabine, and paclitaxel for the treatment of advanced HER2-positive BC especially cancers with central nervous system (CNS) metastasis to reduce the risk of BC recurrence. This article reviewed the pharmacological profiles, efficacy, safety, tolerability, and current clinical trials pertaining to neratinib, with a particular focus on the use of neratinib in patients with metastatic breast cancer (MBC) involving the CNS. We further discussed the use of neratinib for HER2-negative and HER2-mutant breast cancers, and mechanisms of resistance to neratinib. The current evidence suggests that neratinib has promising efficacy in patients with BC which is at least non-inferior compared to previous therapeutic regimens. The most common AE was diarrhea, and the incidence, severity and duration of neratinib-related grade 3 diarrhea can be reduced with loperamide. Of note, neratinib has the potential to effectively control and prevent brain metastasis in patients with advanced BC, providing a therapeutic strategy for HER2-positive BC.

Cancer patients face a higher risk of adverse effects from coronavirus disease 2019 (COVID-19) compared to the general population. However, the safety of restarting antitumor therapy following COVID-19 recovery remains unclear. In this prospective, multicenter study conducted between January 1 and 30 March 2023, 419 eligible cancer patients who had recovered from COVID-19 were screened across four medical centers. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs) during the first cycle of antitumor therapy resumed within 3 months after COVID-19 recovery. Changes in clinical laboratory parameters were assessed as secondary endpoints. A total of 270 eligible participants were included in this study. The common grade 3 or worse TEAEs were fatigue (3.3%), anemia (1.1%), leukopenia (0.7%), and elevated alanine transaminase (0.3%). No severe cardiac toxicity and significant abnormalities on the chest computed tomography (CT) were observed. D-dimer and cardiac troponin I (cTNI) were significantly increased after treatment (p < 0.05). Increased inflammatory cytokines of peripheral blood could be observed after administration of oxaliplatin and trastuzumab. Restarting systemic antitumor therapy in solid tumor patients after COVID-19 recovery is generally safe. Systemic inflammatory and coagulation function of patients should be monitored during treatment.