The treatment combination consisting of Herceptin (trastuzumab) plus Tykerb (lapatinib) provides significant anti-cancer activity in colorectal cancer that overexpresses the human epidermal growth factor receptor 2 (HER2). These results were recently published in The Lancet Oncology.
The HER2 receptor is a protein that is normally found on the surface of several different types of cells in the body. The HER2 receptors span into the cell, and are involved in a biologic pathway that is involved in cellular replication.
Sometimes, a mutation within a gene that is responsible for the HER2 receptor becomes mutated, and too many receptors are produced. This, in turn, results in cells that divide and spread without their normal biologic controls.
Cancer cells that have too many HER2 receptors are referred to as HER2-positive. Fortunately, targeted agents have been developed that bind to different sites within the HER2 pathway, resulting in decreased cell division and spread.
Two of these agents are trastuzumab and lapatinib. The two agents bind along the HER pathway at different points, both producing anti-cancer effects. Both agents are approved for the treatment of HER2-positive breast cancer.
Researchers recently conducted a clinical trial to evaluate the effectiveness of the combination of trastuzumab and lapatinib in advanced, HER2-positive colorectal cancer. The trial included 27 patients with HER2-positive colorectal cancer that had spread from the colon to distant sites in the body. Patients had stopped responding to prior treatment with panitumumab and cetuximab, and genetically had what is referred to as KRAS exon 2 (codons 12 and 13) wild-type cancer.
- Overall, 30% of patients achieved a partial or complete regression of their detectable cancer.
- An additional 44% achieved a stabilization of their cancer.
- No severe side effects attributable to the drug combination were noted.
The researchers of the trial stated that “The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer.”
Future trials further evaluating this treatment combination in this disease will be ongoing.
Reference: Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncology. Published online April 20, 2016. DOI: http://dx.doi.org/10.1016/S1470-2045(16)00150-9. Available at: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00150-9/abstract. Accessed May 10, 2016.