The tyrosine kinase inhibitor poziotinib showed “promising” antitumor activity in patients with advanced HER2 exon 20-mutant non-small cell lung cancer (NSCLC), according to researchers. They reported these results, from a phase 2 trial, in the Journal of Clinical Oncology.

The single-arm study (ClinicalTrials.gov Identifier: NCT03066206) included 30 patients with previously treated, HER2 exon 20-mutant NSCLC. The patients’ median age was 60 years (range, 47-73 years), 73% were women, and 83% were never smokers.

In all, 90% of patients had received prior platinum-based chemotherapy, 80% had received a PD-1 or PD-L1 inhibitor, and 53% had received 2 or more prior lines of therapy.


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Patients received poziotinib at 16 mg per day for 28-day cycles between March 2017 and November 2019. The median follow-up at the time of data cutoff (March 1, 2021) was 14 months.

The investigator-assessed objective response rate (ORR) at 8 weeks was 43%. All 13 responses recorded at 8 weeks were partial responses (PRs). Of these, 8 PRs were confirmed at subsequent imaging. Therefore, the confirmed response rate was 27%. The median duration of response was 5.0 months.

The median progression-free survival (PFS) was 5.5 months. The 6-month PFS rate was 30%, and the 12-month PFS rate was 10%. The median overall survival was 15 months.

Among patients who previously received platinum-based chemotherapy (27 patients), the median PFS was 5 months, the 8-week ORR was 47%, and the confirmed PR rate was 26%.

Among patients who received 2 or more prior lines of therapy (16 patients), the median PFS was 4 months, the 8-week ORR was 31%, and the confirmed PR rate was 19%.

The most common treatment-related adverse events (TRAEs) were skin rash (83%), diarrhea (80%), paronychia (70%), oral mucositis (67%), and dry skin (63%). Severe TRAEs included grade 3 skin rash (47%), diarrhea (20%), and paronychia (20%).

One death, due to pneumonitis, was considered possibly related to treatment.

“Our results show that HER2 exon 20 mutations can be targeted effectively using small tyrosine kinase inhibitors such as poziotinib,” the researchers wrote. “We conclude that poziotinib may be a new therapeutic option for patients with HER2 exon 20-mutant NSCLC, including those who were previously treated with platinum-based chemotherapy and immunotherapy.”

Disclosures: This research was partially supported by Spectrum Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference Elamin YY, Robichaux JP, Carter BW, et al. Poziotinib for patients with HER2 exon 20 mutant non–small-cell lung cancer: Results from a phase II trial. J Clin Oncol. Published online September 22, 2021. doi:10.1200/JCO.21.01113