Cancer Res Treat.  2017 Jan;49(1):10-19. 10.4143/crt.2016.058.

A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR–Tyrosine Kinase Inhibitors

• Han JY
• Lee KH
• Kim SW
• Min YJ
• Cho E
• Lee Y
• Lee SH
• Kim HY
• Lee GK
• Nam BH
• Han H
• Jung J
• Lee JS

• KMID: 2367498
• DOI: http://doi.org/10.4143/crt.2016.058

Abstract

PURPOSE
We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs.
MATERIALS AND METHODS
This single-arm phase II study included EGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms.
RESULTS
Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CA mutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions.
CONCLUSION
Low activity of poziotinib was detected in patients with EGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation.

Keyword

Epidermal growth factor receptor; Poziotinib; Non-small-cell lung carcinoma; T790M; PIK3CA

MeSH Terms

Adenocarcinoma*
Biopsy
Carcinoma, Non-Small-Cell Lung
Disease-Free Survival
Epidermal Growth Factor*
Erlotinib Hydrochloride
Exanthema
Humans
Inflammation
Lung
Phosphotransferases*
Plasma
Receptor, Epidermal Growth Factor*
Stomatitis
Epidermal Growth Factor
Erlotinib Hydrochloride
Phosphotransferases
Receptor, Epidermal Growth Factor

Figure

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  Fig. 1. Best response changes from baseline in tumor lesions: blue (partial response, PR), red (stable disease, SD), and green (progressive disease, PD).

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  Fig. 2. (A) Mutational status in the prestudy tumor tissues. (B) Possible mechanism of acquired resistance to prior epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors.

Reference

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