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01-12-2013 | Original Article

Phase II trial of erlotinib in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations: additive analysis of pharmacokinetics

Authors: Kohei Motoshima, Yoichi Nakamura, Kazumi Sano, Yoji Ikegami, Takaya Ikeda, Kosuke Mizoguchi, Shinnosuke Takemoto, Minoru Fukuda, Seiji Nagashima, Tetsuya Iida, Kazuhiro Tsukamoto, Shigeru Kohno

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2013

Abstract

Background

We conducted a phase II trial of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and evaluated the relationship between plasma concentration and efficacy of erlotinib.

Methods

Patients who were previously treated but naive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), with advanced NSCLC harboring EGFR mutations, were enrolled. Erlotinib was given at 150 mg once daily until disease progression. The primary end point was objective response rate (ORR). Plasma trough levels of erlotinib were measured on Days 2 (D2) and 8 (D8) by high-performance liquid chromatography.

Results

In total, 29 patients were enrolled from September 2008 to January 2011. ORR was 61.5 % (95 % confidence interval [CI] 40.57–79.8) of 26 assessable patients. The median progression-free survival (PFS) and overall survival (OS) were 6.3 months and 16.9 months, respectively. Skin rash was observed in 24 patients, mostly at grade 1 or 2. Grade 2 pneumonitis was observed in one patient. We collected blood samples from 16 patients. The median PFS of the high and low D8/D2 ratio group was 11.2 months and 5.7 months, respectively (p = 0.044, hazard ratio = 0.301, 95 % CI 0.094–0.968).

Conclusion

Erlotinib showed an ORR comparable to that seen in previous studies for patients with NSCLC harboring EGFR mutations, although response, the primary end point, did not reach the predetermined threshold level. The D8/D2 ratio of erlotinib plasma trough levels might be a predictive factor for PFS.

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Title: Phase II trial of erlotinib in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations: additive analysis of pharmacokinetics
Authors: Kohei Motoshima
Yoichi Nakamura
Kazumi Sano
Yoji Ikegami
Takaya Ikeda
Kosuke Mizoguchi
Shinnosuke Takemoto
Minoru Fukuda
Seiji Nagashima
Tetsuya Iida
Kazuhiro Tsukamoto
Shigeru Kohno
Publication date: 01-12-2013
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2013
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2307-6

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Abstract

Background

Methods

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Conclusion

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