A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903

K Ito; M Morise; K Wakuda; O Hataji; T Shimokawaji; K Takahashi; N Furuya; Y Takeyama; Y Goto; T Abe; T Kato; S Ozone; S Ikeda; Y Kogure; T Yokoyama; M Kimura; H Yoshioka; K Murotani; M Kondo; H Saka

doi:10.1016/j.esmoop.2021.100115

A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903

ESMO Open. 2021 Jun;6(3):100115. doi: 10.1016/j.esmoop.2021.100115. Epub 2021 May 10.

Authors

K Ito¹, M Morise², K Wakuda³, O Hataji⁴, T Shimokawaji⁵, K Takahashi⁶, N Furuya⁷, Y Takeyama⁸, Y Goto⁹, T Abe¹⁰, T Kato¹¹, S Ozone¹², S Ikeda¹³, Y Kogure¹⁴, T Yokoyama¹⁵, M Kimura¹⁶, H Yoshioka¹⁷, K Murotani¹⁸, M Kondo⁹, H Saka¹⁹

Affiliations

¹ Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Mie, Japan; Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
² Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. Electronic address: morisem@med.nagoya-u.ac.jp.
³ Division of Thoracic Oncology, Shizuoka Cancer Center, Suntou-gun, Shizuoka, Japan.
⁴ Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Mie, Japan.
⁵ Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
⁶ Department of Respiratory Medicine, Anjo Kosei Hospital, Anjo, Aichi, Japan.
⁷ Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
⁸ Department of Respiratory Medicine, Toyohashi Municipal Hospital, Toyohashi, Aichi, Japan.
⁹ Department of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
¹⁰ Department of Respiratory Medicine, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
¹¹ Division of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
¹² Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
¹³ Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan.
¹⁴ Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
¹⁵ Department of Respiratory Medicine, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Aichi, Japan.
¹⁶ Department of Respiratory Medicine, Toyota Memorial Hospital, Toyota, Aichi, Japan.
¹⁷ Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Osaka, Japan.
¹⁸ Biostatistics Center, Kurume University, Kurume, Fukuoka, Japan.
¹⁹ Department of Respiratory Medicine, Matsunami General Hospital, Kasamatsu, Gifu, Japan.

Abstract

Background: FLAURA, the prospective trial of osimertinib as a first-line therapy compared with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), did not show superior survival benefit for osimertinib in either the subgroup of Asians or the subgroup with the L858R mutation. In addition, the superiority of osimertinib compared with second-generation EGFR-TKI is thus far unclear.

Patients and methods: We reviewed the clinical data of all consecutive patients who were treated with osimertinib or afatinib as first-line therapy between May 2016 and October 2019 from 15 institutions in Japan. We defined the groups based on first-line EGFR-TKI as the afatinib group and the osimertinib group. Outcomes included time to discontinuation of any EGFR-TKI (TD-TKI), overall survival (OS), and time to treatment failure, with propensity score analysis carried out as an exploratory analysis in the survival and subgroup analyses.

Results: A total of 554 patients were enrolled. Data on 326 patients in the osimertinib group, and 224 patients in the afatinib group were analyzed. TD-TKI adjusted by propensity score in the afatinib and osimertinib groups was 18.6 months (95% confidence interval 15.8 to 22.0) and 20.5 months (95% confidence interval 13.8 to not reached), respectively, without significant difference (P = 0.204). OS adjusted by propensity score favored the afatinib group with a significant difference (P = 0.018). Subgroup analysis with propensity score showed that patients with L858R and without brain metastasis had superior survival benefit with afatinib compared with osimertinib (P < 0.001).

Conclusions: TD-TKI in the afatinib group was not significantly prolonged compared with the osimertinib group in the practical data. In the exploratory analysis of patients with L858R-mutated non-small-cell lung cancer without brain metastasis, afatinib showed more benefit in OS over osimertinib.

Keywords: EGFR mutation; afatinib; non-small-cell lung cancer; osimertinib; real world data.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Acrylamides
Afatinib / therapeutic use
Aniline Compounds
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Cohort Studies
ErbB Receptors / genetics
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Prospective Studies

Substances

Acrylamides
Aniline Compounds
osimertinib
Afatinib
EGFR protein, human
ErbB Receptors