一般演題（口演）38
Molecular targeted drugs
座長：吉澤 弘之（厚生連新潟医療センター呼吸器内科）
Molecular targeted drugs
座長：吉澤 弘之（厚生連新潟医療センター呼吸器内科）
O-3-15．Post-marketing observational study of Japanese patients with EGFR mutation-positive non-small cell lung cancer（NSCLC）treated with daily afatinib（interim report）
Masaya Mizushima1・Toshihiro Nukiwa2・Yoichi Nakanishi3・Akihiko Gemma4・Nobuyuki Yamamoto5・Kaori Ochiai6・Masamichi Kaneko1・Hisaya Azuma1・Kazuo Tamura7
Medical Division, Nippon Boehringer Ingelheim Co., Ltd, Tokyo, Japan1；Japan Anti-Tuberculosis Association, Tokyo, Japan2；Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan3；Nippon Medical School, Tokyo, Japan4；Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan5；Statistics Analysis Center, Data Science Center, EPS Corporation, Tokyo, Japan6；General Medical Research Center, School of Medicine, Fukuoka University, Fukuoka, Japan7
Medical Division, Nippon Boehringer Ingelheim Co., Ltd, Tokyo, Japan1；Japan Anti-Tuberculosis Association, Tokyo, Japan2；Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan3；Nippon Medical School, Tokyo, Japan4；Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan5；Statistics Analysis Center, Data Science Center, EPS Corporation, Tokyo, Japan6；General Medical Research Center, School of Medicine, Fukuoka University, Fukuoka, Japan7
Background：Afatinib, an irreversible ErbB family blocker, is approved in Japan for treatment of patients with inoperable or recurrent EGFR mutation-positive NSCLC. This prospective, post-marketing surveillance study was conducted to evaluate the safety and efficacy of daily afatinib use in this setting（NCT02131259）.
Methods：Patients received continuous afatinib at the approved dose（20-50 mg/day）and were observed for 52 weeks following the start of treatment or until premature discontinuation. The primary objective was to evaluate safety.
Results：As of January 2016, 1326 patients were included in the safety analysis（60% female, 81% aged ＜75 years, 87% ECOG PS 0/1, 82% BMI ＜25 kg/m2, 41% current/ex-smoker）. Most patients（97%）had adenocarcinoma, and 65%/26% had EGFR Del19/L858R mutations. The majority（72%）had prior anti-cancer therapy, and 49%/30% had prior gefitinib/erlotinib. The afatinib starting dose was 40 mg for 78% and ＜40 mg for 22% of patients. The most frequently reported adverse drug reactions（ADRs；all grade［grade 3/4］）were diarrhea（78%［12%］）, rash/acne（55%［4%］）, stomatitis（31%［3%］）, and nail effects（29%［2%］）. Median（range）time to initial onset was 5.0（1-402）days for diarrhea, 11.0（1-331）days for rash/acne, 9.0（1-164）days for stomatitis, and 32.5（1-270）days for nail effects. Interstitial lung disease was observed in 53（4%）patients. Serious adverse events（SAEs）were reported in 47% of patients；23% discontinued treatment due to AEs. In subgroup analyses, ADR frequency was associated with starting dose（87/90/95% with 20/30/40 mg afatinib）but was not unfavorably impacted by patient age, performance status, number of prior therapies, or prior administration of EGFR tyrosine kinase inhibitors.
Conclusions：Afatinib was associated with a predictable and generally manageable ADR profile, consistent with previous studies. In clinical practice, close observation of patients and early treatment, particularly for diarrhea, is required to prevent SAEs. Mature evaluation of this study will be performed at the final analysis.
Methods：Patients received continuous afatinib at the approved dose（20-50 mg/day）and were observed for 52 weeks following the start of treatment or until premature discontinuation. The primary objective was to evaluate safety.
Results：As of January 2016, 1326 patients were included in the safety analysis（60% female, 81% aged ＜75 years, 87% ECOG PS 0/1, 82% BMI ＜25 kg/m2, 41% current/ex-smoker）. Most patients（97%）had adenocarcinoma, and 65%/26% had EGFR Del19/L858R mutations. The majority（72%）had prior anti-cancer therapy, and 49%/30% had prior gefitinib/erlotinib. The afatinib starting dose was 40 mg for 78% and ＜40 mg for 22% of patients. The most frequently reported adverse drug reactions（ADRs；all grade［grade 3/4］）were diarrhea（78%［12%］）, rash/acne（55%［4%］）, stomatitis（31%［3%］）, and nail effects（29%［2%］）. Median（range）time to initial onset was 5.0（1-402）days for diarrhea, 11.0（1-331）days for rash/acne, 9.0（1-164）days for stomatitis, and 32.5（1-270）days for nail effects. Interstitial lung disease was observed in 53（4%）patients. Serious adverse events（SAEs）were reported in 47% of patients；23% discontinued treatment due to AEs. In subgroup analyses, ADR frequency was associated with starting dose（87/90/95% with 20/30/40 mg afatinib）but was not unfavorably impacted by patient age, performance status, number of prior therapies, or prior administration of EGFR tyrosine kinase inhibitors.
Conclusions：Afatinib was associated with a predictable and generally manageable ADR profile, consistent with previous studies. In clinical practice, close observation of patients and early treatment, particularly for diarrhea, is required to prevent SAEs. Mature evaluation of this study will be performed at the final analysis.
第57回日本肺癌学会学術集会 2016年12月開催
