Pyrotinib Shows Activity in HER2-Positive Non-Small Cell Lung Cancer
Pyrotinib showed activity in HER2-positive non-small cell lung cancer, both in preclinical experiments and in patients enrolled in a phase 2 trial.
Pyrotinib, an irreversible pan-HER receptor tyrosine kinase inhibitor, showed activity against HER2-positive non-small cell lung cancer (NSCLC) in preclinical experiments and in a phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT02535507).1 The results were published online December 31, 2018, in Annals of Oncology.
Study researchers conducted a series of experiments to determine the activity of pyrotinib in lung cancer. Cell viability and proliferation assays were performed on patient-derived lung cancer organoids that were exposed to pyrotinib. Compared with treatment with afatinib, pyrotinib slowed cell growth more significantly in the disease-model organoids (P = .0038). In xenograft mouse models, pyrotinib slowed tumor growth in a dose-dependent fashion and significantly shrank tumors, altogether demonstrating superior antitumor activity compared with afatinib (P = .0471) and ado-trastuzumab emtansine (T-DM1) (P = .0138).
For the phase 2 study, 15 patients with HER2-positive NSCLC were enrolled and treated with pyrotinib 400 mg. Ten of the 15 patients had HER2 A775_G776insYVMA insertion. The primary end point of the trial was objective response rate (ORR), and secondary end points included progression-free survival (PFS).
Of the 15 patients, 8 (53.3%) had a partial response and 3 (20.0%) had stable disease, yielding an ORR of 53.3%. The median PFS was 6.4 months (95% confidence interval [CI], 1.60-11.20), with a range of 1.7 months to 23.4 months.
Among the 10 patients with HER2 A775_G776insYVMA insertion, the ORR was 50% and PFS was 4.1 months (95% CI, 1.42-6.10). Responses were also seen in patients with HER2 G776C, G776>VC, or L755P. One patient with G776>IC did not respond to treatment.
Nine patients (60%) had adverse events of any grade. No dose modifications occurred as a result of adverse events.
“Pyrotinib's encouraging antitumor activity in patients with HER2 exon 20 mutant lung cancers warrants further evaluation in an ongoing multicenter phase 2 trial,” the study authors wrote in conclusion.
- Wang Y, Jiang T, Qin Z, et al. HER2 exon 20 insertions in non-small cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib [published online December 31, 2018]. Ann Oncol. doi: 10.1093/annonc/mdy542