A prospective, phase II trial of monotherapy with low-dose afatinib for patients with EGFR, mutation-positive, non-small cell lung cancer: Thoracic oncology research group 1632

被引：9

作者：

Noro, Rintaro ^{[1
]}

Igawa, Satoshi ^{[2
]}

Bessho, Akihiro ^{[3
]}

Hirose, Takashi ^{[4
]}

Shimokawa, Tsuneo ^{[5
]}

Nakashima, Masanao ^{[6
]}

Minato, Koichi ^{[7
]}

Seki, Nobuhiko ^{[8
]}

Tokito, Takaaki ^{[9
]}

Harada, Toshiyuki ^{[10
]}

Sasada, Shinji ^{[11
]}

Miyamoto, Shingo ^{[12
]}

Tanaka, Yosuke ^{[13
]}

Furuya, Naoki ^{[14
]}

Kaburagi, Takayuki ^{[15
]}

Hayashi, Hideki ^{[16
]}

Iihara, Hirotoshi ^{[16
,17
]}

Okamoto, Hiroaki ^{[5
]}

Kubota, Kaoru ^{[1
]}

机构：

[1] Nippon Med Coll Hosp, Dept Pulm Med & Oncol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo, Japan

[2] Kitasato Univ, Dept Resp Med, Sch Med, 1-15-1 Kitasato, Sagamihara, Kanagawa, Japan

[3] Japanese Red Cross Okayama Hosp, Dept Resp Med, Kita Ku, 2-1-1 Aoe, Okayama, Japan

[4] Nippon Med Sch, Dept Pulm Med & Med Oncol, Tamanagayama Hosp, 1-7-1 Nagayama, Tama, Tokyo, Japan

[5] Yokohama Municipal Citizens Hosp, Dept Resp Med, Yokohama, Kanagawa, Japan

[6] Shin Yurigaoka Gen Hosp, Dept Resp Med, Asao Ku, 255 Tsuko, Kawasaki, Kanagawa, Japan

[7] Gunma Prefectural Canc Ctr, Dept Resp Med, 617-1 Takahayashinishicho, Ota City, Gunma, Japan

[8] Teikyo Univ, Dept Internal Med, Div Med Oncol, Sch Med,Itabashi Ku, 2-11-1 Kaga, Tokyo, Japan

[9] Kurume Univ, Dept Internal Med, Div Respirol Neurol & Rheumatol, Sch Med, 67 Asahi Machi, Kurume, Fukuoka, Japan

[10] JCHO Hokkaido Hosp, Dept Resp Med, Toyohira Ku, 1-8-3-18 Nakanoshima, Sapporo, Hokkaido, Japan

[11] Tokyo Saiseikai Cent Hosp, Dept Resp Med, Minato Ku, 1-4-17 Mita, Tokyo, Japan

[12] Japanese Red Cross Med Ctr, Dept Med Oncol, Shibuya Ku, 4-1-22 Hiroo, Tokyo, Japan

[13] Nippon Med Sch, Dept Resp Med, Chibahokusoh Hosp, 1715 Kamakari, Inzai City, Chiba, Japan

[14] St Marianna Univ, Div Resp Med, Dept Internal Med, Sch Med, 2-16-1 Sugao, Kawasaki, Kanagawa, Japan

[15] Ibaraki Cent Hosp, Dept Resp Med, 6528 Koibuchi, Kasama, Ibaraki, Japan

[16] Gifu Pharmaceut Univ, Lab Pharm Practice & Social Sci, 1-25-4 Nishi, Gifu, Gifu, Japan

[17] Gifu Univ Hosp, Dept Pharm, 1-1 Yanagido, Gifu, Gifu, Japan

来源：

LUNG CANCER | 2021年 / 161卷

关键词：

EGFR mutation-positive; Low-dose afatinib; Adverse events; Afatinib plasma concentrations; GROWTH-FACTOR RECEPTOR; GEFITINIB TREATMENT; SURVIVAL-DATA; ADENOCARCINOMA; CHEMOTHERAPY;

D O I：

10.1016/j.lungcan.2021.08.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objectives: Afatinib is an effective treatment for patients with epidermal growth factor receptor (EGFR) mutationpositive non-small cell lung cancer (NSCLC). However, the toxicity associated with this agent often leads to dose modifications. The aim of this study was to assess the efficacy, safety and plasma concentrations of low dose afatinib monotherapy in patients with EGFR mutation-positive NSCLC. Patients and Methods: This was a multicenter, single-arm, open-label, phase II trial involving treatment-naive patients with advanced EGFR mutation-positive NSCLC. From March 2017 to September 2018, 53 patients were enrolled from 21 institutions in Japan. Patients initially received afatinib 20 mg/day orally. For patients in whom the tumor progressed within stable disease, the investigators were able to increase the afatinib dose (10 mg increments). The primary endpoint was progression-free survival (PFS). The threshold and expected median PFS was 9.2 and 13.8 months, respectively. Additionally, the correlation of the plasma concentration of low-dose afatinib with clinical outcome and adverse events were evaluated. Results: The median age of patients was 70 years (range: 37-85 years); 28 patients (52.8%) were females. The median duration of the follow-up was 20.8 months. The median PFS, and overall survival were 12.6 months (90% confidence interval [CI]: 9.7-14.3 months), and not reached, respectively. The primary endpoint was met. The objective response rate and disease control rate were 66.0% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9), respectively. Grade >= 3 adverse events occurred in 12 patients (22.6%), including diarrhea in four patients (7.5%). The rate of adverse events was lower than that observed in previous phase III studies of 40 mg afatinib. Conclusion: Based on its promising clinical efficacy and tolerability profile, monotherapy with low-dose afatinib should become one of the standard therapies for EGFR mutation-positive NSCLC.

引用

页码：49 / 54

页数：6

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