A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation

Okayama Lung Cancer Study Group trial 1403

Naohiro Oda, Katsuyuki Hotta, Kiichiro Ninomiya, Daisuke Minami, Eiki Ichihara, Toshi Murakami, Toshihide Yokoyama, Hirohisa Ichikawa, Kenichi Chikamori, Nagio Takigawa, Nobuaki Ochi, Shingo Harita, Yoshinobu Maeda, Katsuyuki Kiura

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: The aim of this study was to evaluate the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration using afatinib in patients with non-small-cell lung cancer (NSCLC) with a sensitive non-T790M EGFR mutation who had received cytotoxic chemotherapy after acquiring resistance to EGFR-TKIs. Methods: Eligible patients had EGFR-mutant tumors resistant to first- or second-generation EGFR-TKIs and an EGFR-TKI-free period with cytotoxic agents. Confirmation of absence of the T790M mutation was required before registration. Afatinib (40 mg/body) was administered daily. The primary endpoint was progression-free survival (PFS). We assumed estimated and threshold PFS times of 3.3 and 1 months, with an α of 0.05 and β of 0.1, respectively. Results: Twelve patients were enrolled from December 2014 to May 2017. The objective response rate and disease control rate were 17% and 84%, respectively. The median PFS time was 4.2 months (95% confidence interval [CI] 2.0–5.8), which met the pre-defined primary endpoint. The median overall survival was 11.6 months (95% CI 9.2-not reached). Grade 3 or worse adverse events included diarrhea (25%), elevated creatinine levels (8%), and hypokalemia (8%), without any treatment-related deaths. Conclusion: EGFR-TKI readministration with afatinib for sensitive EGFR-mutant NSCLC without T790M after resistance to a first- or second-generation EGFR-TKI yielded modest activity with tolerable toxicity. It might be one of the treatment options in patients who do not possess T790M tumors, although further studies in this patient setting are warranted.

Original languageEnglish
JournalCancer Chemotherapy and Pharmacology
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Lung Neoplasms
Cells
Mutation
Disease-Free Survival
Tumors
Confidence Intervals
Disease control
BIBW 2992
Chemotherapy
Hypokalemia
Cytotoxins
Toxicity
Diarrhea
Creatinine
Neoplasms
Drug Therapy
Survival

Keywords

  • Afatinib
  • EGFR mutation
  • EGFR-TKI
  • Non-small-cell lung cancer
  • Readministration
  • T790M

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation : Okayama Lung Cancer Study Group trial 1403. / Oda, Naohiro; Hotta, Katsuyuki; Ninomiya, Kiichiro; Minami, Daisuke; Ichihara, Eiki; Murakami, Toshi; Yokoyama, Toshihide; Ichikawa, Hirohisa; Chikamori, Kenichi; Takigawa, Nagio; Ochi, Nobuaki; Harita, Shingo; Maeda, Yoshinobu; Kiura, Katsuyuki.

In: Cancer Chemotherapy and Pharmacology, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "Purpose: The aim of this study was to evaluate the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration using afatinib in patients with non-small-cell lung cancer (NSCLC) with a sensitive non-T790M EGFR mutation who had received cytotoxic chemotherapy after acquiring resistance to EGFR-TKIs. Methods: Eligible patients had EGFR-mutant tumors resistant to first- or second-generation EGFR-TKIs and an EGFR-TKI-free period with cytotoxic agents. Confirmation of absence of the T790M mutation was required before registration. Afatinib (40 mg/body) was administered daily. The primary endpoint was progression-free survival (PFS). We assumed estimated and threshold PFS times of 3.3 and 1 months, with an α of 0.05 and β of 0.1, respectively. Results: Twelve patients were enrolled from December 2014 to May 2017. The objective response rate and disease control rate were 17{\%} and 84{\%}, respectively. The median PFS time was 4.2 months (95{\%} confidence interval [CI] 2.0–5.8), which met the pre-defined primary endpoint. The median overall survival was 11.6 months (95{\%} CI 9.2-not reached). Grade 3 or worse adverse events included diarrhea (25{\%}), elevated creatinine levels (8{\%}), and hypokalemia (8{\%}), without any treatment-related deaths. Conclusion: EGFR-TKI readministration with afatinib for sensitive EGFR-mutant NSCLC without T790M after resistance to a first- or second-generation EGFR-TKI yielded modest activity with tolerable toxicity. It might be one of the treatment options in patients who do not possess T790M tumors, although further studies in this patient setting are warranted.",
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T1 - A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation

T2 - Okayama Lung Cancer Study Group trial 1403

AU - Oda, Naohiro

AU - Hotta, Katsuyuki

AU - Ninomiya, Kiichiro

AU - Minami, Daisuke

AU - Ichihara, Eiki

AU - Murakami, Toshi

AU - Yokoyama, Toshihide

AU - Ichikawa, Hirohisa

AU - Chikamori, Kenichi

AU - Takigawa, Nagio

AU - Ochi, Nobuaki

AU - Harita, Shingo

AU - Maeda, Yoshinobu

AU - Kiura, Katsuyuki

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: The aim of this study was to evaluate the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration using afatinib in patients with non-small-cell lung cancer (NSCLC) with a sensitive non-T790M EGFR mutation who had received cytotoxic chemotherapy after acquiring resistance to EGFR-TKIs. Methods: Eligible patients had EGFR-mutant tumors resistant to first- or second-generation EGFR-TKIs and an EGFR-TKI-free period with cytotoxic agents. Confirmation of absence of the T790M mutation was required before registration. Afatinib (40 mg/body) was administered daily. The primary endpoint was progression-free survival (PFS). We assumed estimated and threshold PFS times of 3.3 and 1 months, with an α of 0.05 and β of 0.1, respectively. Results: Twelve patients were enrolled from December 2014 to May 2017. The objective response rate and disease control rate were 17% and 84%, respectively. The median PFS time was 4.2 months (95% confidence interval [CI] 2.0–5.8), which met the pre-defined primary endpoint. The median overall survival was 11.6 months (95% CI 9.2-not reached). Grade 3 or worse adverse events included diarrhea (25%), elevated creatinine levels (8%), and hypokalemia (8%), without any treatment-related deaths. Conclusion: EGFR-TKI readministration with afatinib for sensitive EGFR-mutant NSCLC without T790M after resistance to a first- or second-generation EGFR-TKI yielded modest activity with tolerable toxicity. It might be one of the treatment options in patients who do not possess T790M tumors, although further studies in this patient setting are warranted.

AB - Purpose: The aim of this study was to evaluate the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration using afatinib in patients with non-small-cell lung cancer (NSCLC) with a sensitive non-T790M EGFR mutation who had received cytotoxic chemotherapy after acquiring resistance to EGFR-TKIs. Methods: Eligible patients had EGFR-mutant tumors resistant to first- or second-generation EGFR-TKIs and an EGFR-TKI-free period with cytotoxic agents. Confirmation of absence of the T790M mutation was required before registration. Afatinib (40 mg/body) was administered daily. The primary endpoint was progression-free survival (PFS). We assumed estimated and threshold PFS times of 3.3 and 1 months, with an α of 0.05 and β of 0.1, respectively. Results: Twelve patients were enrolled from December 2014 to May 2017. The objective response rate and disease control rate were 17% and 84%, respectively. The median PFS time was 4.2 months (95% confidence interval [CI] 2.0–5.8), which met the pre-defined primary endpoint. The median overall survival was 11.6 months (95% CI 9.2-not reached). Grade 3 or worse adverse events included diarrhea (25%), elevated creatinine levels (8%), and hypokalemia (8%), without any treatment-related deaths. Conclusion: EGFR-TKI readministration with afatinib for sensitive EGFR-mutant NSCLC without T790M after resistance to a first- or second-generation EGFR-TKI yielded modest activity with tolerable toxicity. It might be one of the treatment options in patients who do not possess T790M tumors, although further studies in this patient setting are warranted.

KW - Afatinib

KW - EGFR mutation

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KW - Non-small-cell lung cancer

KW - Readministration

KW - T790M

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