A Phase IIIb Open-Label, Single-Arm Study of Afatinib in EGFR TKI-Naïve Patients with EGFRm+ NSCLC: Final Analysis, with a Focus on Patients Enrolled at Sites in China

Hai-Yan Tu, Jifeng Feng, Meiqi Shi, Jun Zhao, Yuyan Wang, Jianhua Chang, Jialei Wang, Ying Cheng, Jing Zhu, Eng-Huat Tan, Kai Li, Yiping Zhang, Victor Lee, Cheng-Ta Yang, Wu-Chou Su, David Chi-Leung Lam, B J Srinivasa, Senthil Rajappa, Ching-Liang Ho, Kwok Chi Lam, Yi Hu, Shailesh Arjun Bondarde, Xiaoqing Liu, Yahui Tian, Zhiyi Xue, Agnieszka Cseh, Dennis Chin-Lun Huang, Caicun Zhou, Yi-Long Wu, Hai-Yan Tu, Jifeng Feng, Meiqi Shi, Jun Zhao, Yuyan Wang, Jianhua Chang, Jialei Wang, Ying Cheng, Jing Zhu, Eng-Huat Tan, Kai Li, Yiping Zhang, Victor Lee, Cheng-Ta Yang, Wu-Chou Su, David Chi-Leung Lam, B J Srinivasa, Senthil Rajappa, Ching-Liang Ho, Kwok Chi Lam, Yi Hu, Shailesh Arjun Bondarde, Xiaoqing Liu, Yahui Tian, Zhiyi Xue, Agnieszka Cseh, Dennis Chin-Lun Huang, Caicun Zhou, Yi-Long Wu

Abstract

Background: Afatinib has been shown as a suitable option for the treatment of epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC) in randomized controlled trials. However, patients treated in real-world clinical practice, including elderly patients, and those with brain metastases or poor Eastern Cooperative Oncology Group (ECOG) performance statuses, are often excluded from these studies.

Objective: To report the final results, with a particular focus on patients enrolled in China, from a prospective phase IIIb, "near real-world" study of afatinib in tyrosine kinase inhibitor (TKI)-naïve Asian patients with EGFRm+ NSCLC.

Patients and methods: NCT01953913 was conducted at 34 centers across Asia. Entry criteria were broad to reflect real-world settings. Patients received afatinib 40 mg/day until tumor progression, lack of clinical benefit, or poor tolerability. Assessments included safety, time to symptomatic progression (TTSP), and progression-free survival (PFS).

Results: 541 patients were treated, of whom 412 were enrolled in China. Dose reductions were implemented in 28.7% of patients overall, and 17.7% of patients from China. Safety findings were consistent with phase III studies of afatinib. Median TTSP in all patients was 14.0 months (95% CI 12.9-15.9), and median PFS was 12.1 months (95% CI 11.0-13.6). Median TTSP (13.8 months, 95% CI 12.7-16.1) and PFS (11.4 months, 95% CI 10.9-13.7) were similar in patients from China to the overall population. Among patients from China who had dose reductions, TTSP was numerically longer than in those who did not (16.4 vs. 13.8 months; P = 0.0703), while PFS was significantly longer (13.9 vs. 11.1 months; P = 0.0275). Among patients from China with brain metastases, TTSP was numerically shorter than in those without (11.0 vs. 14.4 months; P = 0.0869), whereas PFS was significantly shorter (9.2 vs. 12.9 months; P = 0.0075).

Conclusions: Safety data for afatinib when used in a "near real-world" setting in patients with EGFRm+ NSCLC was consistent with the known safety profile of afatinib. Supporting efficacy data of afatinib were provided in all patients, and in those enrolled in China. Tolerability-guided afatinib dose reduction allowed patients to remain on treatment and continue to experience clinical benefit.

Trial registration number and date of registration: NCT01953913 (1 October 2013).

Conflict of interest statement

Y-LW reports receiving honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Hengrui, Merck Sharp & Dohme, Pfizer, Roche, Sanofi; and receiving grants or funds from AstraZeneca, BMS, and Pfizer. KCL declares receiving honoraria (outside the submitted work) from Pifzer, AstraZeneca, Eli Lily, Roche. YT is employed by Boehringer Ingelheim (China) Investment Co., Ltd. ZX is employed by Boehringer Ingelheim (China) Investment Co., Ltd. AC was employed by Boehringer Ingelheim International GmbH. DC-LH was employed by Boehringer Ingelheim Taiwan Limited and is currently employed with Merck Sharp & Dohme (I.A.) LLC, Taiwan Branch. All the remaining authors declare no potential conflicts of interest.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Disposition diagram. aIncludes patients who switched to commercial drug. AE adverse event
Fig. 2
Fig. 2
a Most frequently reported treatment-related adverse events (TRAEs) of any grade and grade ≥ 3 intensity; b SAEs reported in the overall population. aGrouped terms. ALT alanine aminotransferase, AST aspartate aminotransferase, CNS central nervous system, PPE palmar-plantar erythrodysesthesia, SAEs serious adverse events
Fig. 3
Fig. 3
Kaplan–Meier curves for a TTSP in the overall population; b TTSP in patients enrolled in China; c PFS in the overall population; and d PFS in patients enrolled in China. PFS progression-free survival, TTSP time to symptomatic progression

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