Dr. Corcoran on Targeting HER2 Amplification in CRC

Ryan B. Corcoran, MD, PhD, associate professor of medicine, Harvard Medical School, and associate professor, Cancer Center, Massachusetts General Hospital, discusses the presence of HER2 amplification in metastatic colorectal cancer (mCRC).

HER2 is amplified in about 4% of all cases of mCRC, says Corcoran. HER2 is well-known as a target in breast and gastric cancers, where it is more widely overexpressed and amplified; however, HER2 also occurs in RAS and BRAF wild-type CRC.

Although this group of patients would typically receive EGFR-directed therapies, research has shown that those with CRC whose tumors have HER2 amplification do not respond well to EGFR antibodies. As such, rather than being a marker of resistance, HER2 has become a promising therapeutic target in CRC, says Corcoran.

Three studies have combined the anti-HER2 agent trastuzumab (Herceptin) with either pertuzumab (Perjeta), another anti-HER2 antibody, or 1 of 2 small molecule inhibitors, lapatinib (Tykerb) or tucatinib, adds Corcoran. Data from some of these studies have shown response rates ranging from 30% to 45% in this patient population with promising durability.

Although HER2 is a rare target, it is worth considering when assessing later-line therapy options for patients with CRC, concludes Corcoran.