HER2-Targeted Therapy With Trastuzumab Deruxtecan in Lung Cancer
Posted: Tuesday, June 30, 2020
According to a first-in-human clinical trial published in Cancer Discovery, the HER2-targeted therapy fam-trastuzumab deruxtecan-nxki (T-DXd) showed preliminary antitumor activity in advanced solid tumors—including HER2-mutant and HER2-expressing non–small cell lung cancer (NSCLC)—other than breast and gastric cancers. According to Bob T. Li, MD, of the Memorial Sloan Kettering Cancer Center, New York, and colleagues, additional research is warranted with this agent for patients with both HER2-overexpression and HER2-mutant solid tumors.
“The objective response rate of > 70% with T-DXd reported here in 11 patients with HER2-mutant NSCLC is particularly promising, with responders observed across HER2 mutation subtypes including exon 20 insertions and extracellular domain point mutations,” the authors commented.
In this phase I study, the authors reviewed data from 60 patients with HER2-overexpressing non-breast/non-gastric solid tumors and/or HER2-mutated solid tumors. Of the total, 18 had NSCLC, 20 had colorectal cancer, and 22 were categorized as having “other” cancer types. In addition, two cases of HER2-mutated breast cancer were also included. A total of 59 patients received at least one dose of 6.4 mg/kg of T-DXd.
Following the treatment, the overall objective response rate was 28.3%, and the median progression-free survival was 7.2 months. Patients with six tumor types had confirmed responses. T-DXd demonstrated activity in a mixed population and particularly in HER2-mutant NSCLC.
The investigators acknowledged the limitations of their study. “This was a nonrandomized, phase I study with a heterogeneous patient population and a relatively limited sample size. Therefore, the results should be viewed as exploratory, with results to be confirmed in ongoing, larger, tumor type–specific phase II studies, including in colorectal cancer,” they noted.
Disclosure: The study authors’ disclosure information can be found at cancerdiscovery.aacrjournals.org.