Novel treatment approaches for HER2 positive solid tumors (excluding breast cancer)

Human epidermal growth factor 2 (HER2) alterations (protein overexpression, gene amplification and mutation) play a key role in oncogenesis and are more likely correlated to poorer outcome in solid tumors. We reviewed recently published studies in the last 18 months on novel treatment approaches for HER2 positive solid tumors (excluding breast cancer).

Results of clinical studies assessing anti-HER2 therapies have been recently issued.One of the most promising drugs is transtuzumab deruxtecan, an antibody-drug conjugate which demonstrated clinically meaningful activity in gastric or gastroesophageal junction cancer and colorectal cancers.Small molecules such as poziotinib, pyrotinib, neratinib, which target both epidermal growth factor receptor (EGFR) and HER2 also showed promising activity, especially in heavily pretreated ERRB2-mutated non-small cell lung cancer (NSCLC) cancer patients. Yet, these findings need to be confirmed in confirmatory randomized trials with larger cohorts.Trastuzumab-based combinations with chemotherapy or immune checkpoint inhibitors are under development with promising results, but not in all HER2 tumors. Emerging adverse events with anti-HER2 are interstitial pneumopathy and diarrhea.

Tyrosine kinase inhibitors, antibody drug conjugate in monotherapy and combinations are emerging strategies in many HER2-positive cancers; HER2 therapies are now part of standard of care of HER2-amplified gastric or gastroesophageal junction cancer. Data are pending on several unmet medical needs.