Tyrosine Kinase Inhibitor Combination Therapy for HER2-Mutated NSCLC
Posted: Monday, March 15, 2021
The novel EGFR/HER2 dual tyrosine kinase inhibitor pyrotinib in combination with the VEGFR inhibitor apatinib appears to be safe and demonstrates antitumor activity in patients with heavily pretreated HER2-mutated non–small cell lung cancer (NSCLC), according to Yan Wang, MD, of the Tongji University School of Medicine, Shanghai, China, and colleagues. These phase II trial results were presented in January 2021 during the virtual edition of the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer Singapore (WCLC; Abstract JICC01.15).
“Currently, there have been no approved tyrosine kinase inhibitors for NSCLC harboring HER2 mutations, resulting in an unmet need of this molecular entity,” the investigators commented. In this trial, a total of 14 patients with stage IV metastatic HER2-mutated lung adenocarcinomas were administered 400 mg of pyrotinib and 250 mg of apatinib daily.
Among all evaluable patients, the objective response rate was 35.7%. The objective response rates (40.0% vs. 33.3%) and the median duration of progression-free survival (6.6 vs. 8.0 months; P = .623) did not seem to differ between patients with and without brain metastases. In all subgroups of patients (10 with exon 20 insertions, 2 with missense mutations, and 2 with amplifications), the disease control rate was 100%.
The median duration of response, progression-free survival, and overall survival were 5.3, 8.0, and 12.9 months, respectively. The objective response rates were 28.6% and 42.9% in patients who received pyrotinib plus apatinib as a second- and third- or above-line treatment, respectively; the median duration of progression-free survival did not seem to differ between these two subgroups (8.8 vs. 6.1 months; hazard ratio = 0.362; P = .144). Diarrhea (grade 3: 7.1%; grade 2: 64.3%), hypertension (grade 2: 21.4%; grade 1: 50.0%), and anorexia (grade 1: 57.1%) were the most common treatment-related adverse events. Treatment-related deaths were not reported.
Disclosure: For full disclosures of the study authors, visit wclc2020.iaslc.org.
