HER2 (Human epidermal growth factor receptor 2) is a receptor in the same family of proteins as EGFR.
The gene for HER2 (referred to as HER2 or HER2/neu) is frequently amplified in breast cancers, and amplification of HER2 is a common marker of poor prognosis. In addition, recent studies have shown that high expression of HER2 in NSCLC cells is also associated with a poor outcome (60).
Trastuzumab (Herceptin), one of the earliest molecular targeted cancer therapies, is approved by the FDA for the treatment of breast cancer patients whose tumors contain HER2 amplifications or HER2 overexpression (referred to as HER2+, or "HER2-positive"). Given that approximately 25% of breast cancers are HER2+, trastuzumab has been extremely beneficial when administered in combination with chemotherapy for patients with HER2+ breast cancer (61).
Ongoing trials evaluating the efficacy of HER2 inhibitors in NSCLC patients with elevated HER2 expression have shown variable results. One trial found that trastuzumab provided no benefit in NSCLC patients with high HER2 expression (62). However, another study found that trastuzumab in combination with chemotherapy may be effective in NSCLC patients who have HER2 amplifications or mutations (63).
A newer drug, lapatinib, inhibits both HER2 and EGFR. A recent study showed that the combination of lapatinib and the anti-EGFR antibody cetuximab are effective in killing NSCLC cells that are resistant to EGFR inhibitors (64). Phase I and II clinical trials of lapatinib in combination with chemotherapy are currently in progress for NSCLC patients. Trials of trastuzumab and lapatinib together are in progress in patients with breast cancer but not NSCLC.