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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.
Cancer Chemother Pharmacol 2018; 82(6):1031-1038CC

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.

Authors+Show Affiliations

Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan. khotta@okayama-u.ac.jp. Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho Kita-ku, Okayama, Okayama, 700-8558, Japan. khotta@okayama-u.ac.jp.Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan.Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.Department of Respiratory Medicine, Himeji Red Cross Hospital, Himeji, Japan. Department of Respiratory Medicine, Onomichi City Hospital, Onomichi, Japan.Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, Japan.Department of Medical Oncology, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.Department of Respiratory Medicine, Okayama Saiseikai General Hospital, Okayama, Japan. Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan.Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30276451

Citation

Oda, Naohiro, et al. "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." Cancer Chemotherapy and Pharmacology, vol. 82, no. 6, 2018, pp. 1031-1038.
Oda N, Hotta K, Ninomiya K, et al. 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. Cancer Chemother Pharmacol. 2018;82(6):1031-1038.
Oda, N., Hotta, K., Ninomiya, K., Minami, D., Ichihara, E., Murakami, T., ... Kiura, K. (2018). 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. Cancer Chemotherapy and Pharmacology, 82(6), pp. 1031-1038. doi:10.1007/s00280-018-3694-5.
Oda N, et al. 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. Cancer Chemother Pharmacol. 2018;82(6):1031-1038. PubMed PMID: 30276451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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: Okayama Lung Cancer Study Group trial 1403. AU - Oda,Naohiro, AU - Hotta,Kastuyuki, 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, Y1 - 2018/10/01/ PY - 2018/06/30/received PY - 2018/09/24/accepted PY - 2018/10/3/pubmed PY - 2019/8/29/medline PY - 2018/10/3/entrez KW - Afatinib KW - EGFR mutation KW - EGFR-TKI KW - Non-small-cell lung cancer KW - Readministration KW - T790M SP - 1031 EP - 1038 JF - Cancer chemotherapy and pharmacology JO - Cancer Chemother. Pharmacol. VL - 82 IS - 6 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. SN - 1432-0843 UR - https://www.unboundmedicine.com/medline/citation/30276451/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_ L2 - https://dx.doi.org/10.1007/s00280-018-3694-5 DB - PRIME DP - Unbound Medicine ER -