Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B).

Content Provider	Europe PMC
Author	Tsubata, Yukari Watanabe, Kana Saito, Ryota Nakamura, Atsushi Yoshioka, Hiroshige Morita, Mami Honda, Ryoichi Kanaji, Nobuhiro Ohizumi, Satoshi Jingu, Daisuke Nakagawa, Taku Nakazawa, Kensuke Mouri, Atsuto Takeuchi, Susumu Furuya, Naoki Akazawa, Yuki Miura, Kiyotaka Ichihara, Eiki Maemondo, Makoto Morita, Satoshi Kobayashi, Kunihiko Isobe, Takeshi
Abstract	BackgroundOsimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown.MethodsEnrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety.ResultsThirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations.ConclusionOsimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.
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ISSN	13419625
Journal	International Journal of Clinical Oncology [Int J Clin Oncol]
Volume Number	27
DOI	10.1007/s10147-021-02043-2
PubMed Central reference number	PMC8732858
Issue Number	1
PubMed reference number	34643820
e-ISSN	14377772
Language	English
Publisher	Springer Singapore
Publisher Date	2021-10-13
Publisher Place	Singapore
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2021
Subject Keyword	EGFR T790M Non-small-cell lung cancer Osimertinib Phase II Poor performance status
Content Type	Text
Resource Type	Article
Subject	Hematology Surgery Oncology