Dr. Basu-Mallick on Established and Emerging Biomarker-Directed Therapies in CRC

Atrayee Basu-Mallick, MD, a medical oncologist at Sidney Kimmel Cancer Center, and clinical assistant professor at the Thomas Jefferson University, highlights established and emerging biomarker-directed therapies in colorectal cancer (CRC).

Approximately 40% of patients with CRC have KRAS wild-type disease and are able to receive treatment with established therapies such as cetuximab (Erbitux) and panitumumab (Vectibix), Basu-Mallick says. Additionally, approximately 8% of patients have a BRAF mutation, the majority of whom have poor outcomes. For patients who have BRAF wild-type disease, the median survival is about 13 months, Basu-Mallick adds.

Moreover, patients with a BRAF mutation are relatively chemotherapy refractory, or have short responses to chemotherapy. Due to this, a combination of encorafenib (Braftovi) plus cetuximab or a triplet regimen comprised of encorafenib, cetuximab, and binimetinib (Mektovi) can be utilized. However, the triplet regimen is not frequently used, as the outcomes achieved with the 3-drug regimen have proven to be similar to those seen with the doublet regimen, Basu-Mallick explains. For patients who have HER2-positive disease, trastuzumab (Herceptin) plus pertuzumab (Perjeta), as well as trastuzumab plus lapatinib (Tykerb), have elicited a favorable overall response rate (ORR).

The phase 2 DESTINY-CRC01 trial (NCT03384940), which examined fam-trastuzumab deruxtecan-nxki (Enhertu), was unique in that it enrolled patients who were previously treated with an anti-HER2 therapy, Basu Mallick says. It was the first trial in which patients with CRC who had previously received HER2-targeted therapy could receive further HER2-directed treatment, according to Basu-Mallick. The ORR observed with the antibody-drug conjugate in patients who had previously received treatment was similar to that reported in the overall patient population, at 43.8% and 45.3%, respectively, Basu-Mallick concludes.