ESMO 2021: Use of Poziotinib for NSCLC Harboring HER2 Exon 20 Mutations Under Study
Posted: Friday, October 1, 2021
The phase II ZENITH20-4 study, which is assessing the safety and efficacy of poziotinib in newly diagnosed patients with non–small cell lung cancer (NSCLC) with HER2 exon 20 mutation, was performed by Robin Cornelissen, MD, PhD, of Erasmus MC University Medical Center, Rotterdam, Netherlands, and colleagues. Although the study is ongoing, their initial results showing “clinically meaningful” efficacy with the new-generation tyrosine kinase inhibitor were presented during the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract LBA46).
This study enrolled 71 patients with NSCLC who had HER2 exon 20 insertion mutations. Participants were stratified into cohorts 1, 2, 3, and 4 depending on previous EGFR treatment, previous HER2 treatment, naive to EGFR treatment, and naive to HER2 treatment, respectively. Poziotinib was administered at 16 mg once (n = 48) or 8 mg twice (n = 23) daily in cohort 4, allowing for dose interruptions and reductions. The twice-daily group is still enrolling.
The median age of patients who received poziotinib once daily was 61 years, and the majority were White (75%); nonsmokers, females, and patients with an Eastern Cooperative Oncology Group performance score of 1 made up 69%, 54%, and 65% of this cohort, respectively. The primary endpoint—objective response rate—was 44%, although two patients had a response that was not confirmed. Additionally, the median duration of response was 5.4 months, with three patients continuing treatment, and the disease control rate was 75%.
The median progression-free survival was 5.6 months. Dose interruptions were recorded in 88% of patients, 76% experienced dose reductions, and treatment discontinuation due to treatment-related adverse events affected 12%. Grade 3 or higher treatment-related adverse events such as rash (35%), stomatitis (20%), diarrhea (14%), and paronychia (8%) were among the most common with the use of poziotinib.
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
