Rechallenge of afatinib for EGFR-mutated non-small cell lung cancer previously treated with osimertinib: a multicenter phase II trial protocol (REAL study)

被引:7
作者
Araki, Taisuke [1 ]
Kanda, Shintaro [2 ,14 ]
Komatsu, Masamichi [1 ]
Sonehara, Kei [1 ]
Tateishi, Kazunari [1 ]
Takada, Munetake [3 ]
Kato, Akane [4 ]
Yamamoto, Manabu [5 ]
Nishie, Kenichi [6 ]
Hama, Mineyuki [7 ]
Agatsuma, Toshihiko [8 ]
Kakizaki, Yumiko [9 ]
Yoshiike, Fumiaki [1 ,10 ]
Matsuo, Akemi [1 ,11 ]
Chiaki, Tomoshige [1 ,2 ,12 ]
Samizo, Kanae [1 ,3 ,13 ]
Takagi, Yoshiko [1 ,3 ,13 ]
Yamaura, Maki [13 ]
Hanaoka, Masayuki [1 ]
Koizumi, Tomonobu [2 ]
机构
[1] Shinshu Univ, Dept Internal Med 1, Sch Med, Matsumoto, Japan
[2] Shinshu Univ, Dept Hematol & Med Oncol, Sch Med, Matsumoto, Japan
[3] Jiseikai Aizawa Hosp, Dept Resp Med, Matsumoto, Japan
[4] Ina Cent Hosp, Dept Resp Med, Ina, Japan
[5] Japanese Red Cross Soc, Nagano Hosp, Dept Resp Med, Nagano, Japan
[6] Iida Municipal Hosp, Dept Resp Med, Iida, Japan
[7] Japanese Red Cross Soc, Suwa Hosp, Dept Resp Med, Suwa, Japan
[8] Shinshu Ueda Med Ctr, Dept Resp Med, Ueda, Japan
[9] Yamanashi Prefectural Cent Hosp, Lung Canc & Resp Dis Ctr, Kofu, Japan
[10] Nagano Municipal Hosp, Dept Resp Med, Nagano, Japan
[11] Shinonoi Gen Hosp, Minami Nagano Med Ctr, Dept Internal Med, Nagano, Japan
[12] Hokushin Gen Hosp, Dept Resp Med, Nakano, Japan
[13] Shinshu Univ Hosp, Ctr Clin Res, Matsumoto, Japan
[14] Shinshu Univ, Dept Hematol & Med Oncol, Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan
关键词
Non-small cell lung cancer (NSCLC); EGFR-TKI; afatinib; osimertinib; rechallenge; CHEMOTHERAPY; ERLOTINIB; MUTATIONS; GEFITINIB;
D O I
10.21037/tlcr-23-12
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC) and contributed to the development of precision medicine. Osimertinib is a standard first-line (1L) treatment for EGFR-mutated NSCLC and has demonstrated superior survival benefits over previous-generation TKIs. However, resistance to osimertinib is nearly inevitable, and subsequent treatment strategies remain unmet medical needs in this setting. Afatinib, a second-generation EGFR-TKI, exhibits activity against certain uncommon EGFR mutation types in the 1L setting. There are a few case reports on the efficacy of afatinib against EGFR-dependent resistance after osimertinib treatment, although these have not been prospectively investigated. Methods: The present phase II, single-arm multicenter trial aims to verify the efficacy and safety of afatinib rechallenge after 1L osimertinib resistance. Patients (aged & GE;20 years) with advanced or recurrent nonsquamous NSCLC harboring drug-sensitive EGFR mutations (deletion of exon 19 or L858R) who were previously treated with 1L osimertinib and second-line chemotherapy other than TKIs are considered eligible. Undergoing next-generation sequence-based comprehensive genomic profiling is one of the key inclusion criteria. The primary endpoint is the objective response rate; the secondary endpoints are progression-free survival, overall survival, and tolerability. Thirty patients will be recruited in December 2023. Discussion: The results of this study may promote incorporating afatinib rechallenge into the treatment sequence after 1L osimertinib resistance, a setting in which concrete evidence has not been yet established. Registration: UMIN Clinical Trial Registry: UMIN000049225.
引用
收藏
页码:1320 / 1327
页数:8
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