Poziotinib in Previously Treated Patients With NSCLC and HER2 Exon 20 Insertion Mutations

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In a cohort of the phase II ZENITH20-2 trial reported in the Journal of Clinical Oncology, Le et al found that the tyrosine kinase inhibitor poziotinib produced responses in previously treated patients with non–small cell lung cancer (NSCLC) and HER2 exon 20 insertion mutations.

Study Details

In the international multicenter trial, 90 patients enrolled between October 2017 and March 2021 received poziotinib at 16 mg once daily for up to 24 months. Patients had received a median of two prior lines of therapy (range = 1–6). The primary endpoint was objective response rate on independent review committee assessment.


Median follow-up was 9.0 months (range = 0–17.6 months). Objective responses (all partial) were observed in 25 patients (27.8%, 95% confidence interval [CI] = 18.9%–38.2%). An additional 38 patients (42.2%) had stable disease. Disease control was observed in 63 patients (70.0%, 95% CI = 59.4%–79.2%). Tumor reduction (median = 22%) was observed in 74% of patients. Median time to response was 32 days (range = 23–183 days). Median duration of response was 5.1 months (95% CI = 4.2–5.5 months), with 24% of responses lasting ≥ 6 months. Median progression-free survival was 5.5 months (95% CI = 3.9–5.8 months), with a 6-month rate of 37.8% (95% CI = 25.5%–50.0%). Overall, clinical benefit was observed irrespective of number of lines or types of prior therapy, presence of central nervous system metastasis, and types of HER2 mutations.

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in 75 patients (83.3%), including grade 4 events in 4 (4.4%). The most common were rash (48.9%), diarrhea (25.6%), and stomatitis (24.4%). Dose reductions were required in 76.7% of patients, with a median relative dose intensity of 71.5%. Treatment-related serious adverse events occurred in 14.4% of patients, most commonly rash (3.3%) and asthenia, diarrhea, dehydration, and stomatitis (2.2% each). Treatment was discontinued due to treatment-related adverse events in 13.3% of patients. One patient died due to a treatment-related adverse event (pneumonia).

The investigators concluded, “Poziotinib demonstrates antitumor activity in previously treated patients with HER2 exon 20 insertion–[mutated] NSCLC.”

Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Spectrum Pharmaceuticals. For full disclosures of the study authors, visit

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