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Poziotinib, a Tyrosine Kinase Inhibitor, for HER2 Exon 20–Mutant NSCLC


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In a single-center phase II trial reported in the Journal of Clinical Oncology, Elamin et al found that the tyrosine kinase inhibitor poziotinib showed activity in previously treated patients with HER2 exon 20–mutant advanced non–small cell lung cancer (NSCLC).

As related by the investigators, poziotinib, an irreversible covalent tyrosine kinase inhibitor, shares a backbone with afatinib and dacomitinib; however, its smaller size and greater flexibility may allow the drug to circumvent steric hindrance in the drug-binding pocket induced by HER2 or EGFR exon 20 insertions.

Study Details

A total of 30 patients at The University of Texas MD Anderson Cancer Center initiated poziotinib at a dose of 16 mg/d in 28-day cycles between March 2017 and November 2019. Treatment was continued until disease progression or unacceptable toxicity; continuation beyond progression was permitted if clinical benefit was observed according to investigator judgment. Two patients had received no prior systemic therapy; 90% had received prior platinum-based chemotherapy, 80% had received prior PD-1 or PD-L1 inhibitor treatment, and 53% had received two or more lines of systemic therapy.

KEY POINTS

  • Confirmed objective response was observed in 27% of patients.
  • The confirmed response rate in patients with prior platinum-based therapy was 26%.

Responses

Median follow-up at the time of data analysis (data cutoff in March 2021) was 14 months (range = 2.0–43 months). Investigator-assessed objective responses (all partial) were observed in 13 patients (43%, 95% confidence interval [CI] = 25%–63%) at 8 weeks; among the 13 patients with response at 8 weeks, 8 had confirmed response at subsequent imaging, resulting in a confirmed response rate of 27% (95% CI = 12%–46%).

The disease control rate was 73%. Median duration of response was 5 months (95% CI = 4.0 months–not estimable). Median progression-free survival was 5.5 months (95% CI = 4.0–7.0 months), with rates at 6 and 12 months of 30% and 10%, respectively. Median overall survival was 15 months (95% CI = 9.0 months–not estimable).

Among the 27 patients who had received prior platinum-based chemotherapy, median progression-free survival was 5 months (95% CI = 2.0–6.0 months). The 8-week objective response rate was 47% (95% CI = 25%–59%), with a confirmed response rate of 26% (95% CI = 13%–45%).

Adverse Events

The most common treatment-related adverse events of any grade were skin rash (83%), diarrhea (80%), paronychia (70%), oral mucositis (67%), and dry skin (63%). The most common grade 3 treatment-related adverse events were skin rash (47%), diarrhea (20%), paronychia (20%), and oral mucositis (10%); no grade 4 events were observed. Death considered possibly related to treatment occurred in one patient, due to pneumonitis.

The investigators concluded, “Poziotinib showed promising antitumor activity in patients with HER2 exon 20–mutant NSCLC, including patients who had previously received platinum-based chemotherapy.”

John V. Heymach, MD, PhD, of the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Conquer Cancer Foundation, Lung Cancer Research Foundation, Spectrum Pharmaceuticals, and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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