Min Hwan Kim1, Hye Ryun Kim1, Byoung Chul Cho1, Mi Kyung Bae2, Eun Young Kim3, Chang Young Lee2, Jae Seok Lee4, Dae Ryong Kang5, Joo Hang Kim6. 1. Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea. 5. Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea. 6. Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: kjhang@yuhs.ac.
Abstract
OBJECTIVES: The aim of this study is to evaluate the predictive impact of cigarette smoking on treatment outcomes of EGFR-tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma patients with activating EGFR mutations. METHODS: We retrospectively analyzed 222 consecutive recurrent or unresectable lung adenocarcinoma patients who harbored activating EGFR mutations (exon 19 deletion or exon 21 L858R) and had received gefitinib or erlotinib. Detailed smoking histories were obtained from all patients according to a standard protocol. RESULTS: Of 222 EGFR-mutated patients, 65.3% were never-smokers, 19.8% were smokers with < 30 pack-years, and 14.9% were smokers with ≥ 30 pack-years smoking dosage. The disease control rate (DCR) and objective response rate (ORR) of smokers with ≥ 30 pack-years were significantly lower than never-smokers and smokers with < 30 pack-years (DCR, 78.8% vs. 93.1%, p = 0.016; ORR, 45.5% vs. 62.4%, p = 0.020). Smokers with ≥ 30 pack-years showed significantly shorter PFS than never-smokers (6.4 vs. 11.8 months, p = 0.001) and smokers with < 30 pack-years (6.4 vs. 11.4 months, p = 0.033), as well as shorter overall survival from the time of metastatic diagnosis than never-smokers (33.6 vs. 46.2 months, p = 0.003). There was no survival difference between smokers with < 30 pack-year and never smokers. In the multivariate analysis adjusted for age, sex, performance status, initial stage, and line of EGFR-TKI, the presence of smoking dosage ≥ 30 pack-years was an independent predictive factor for the disease progression to EGFR-TKIs (hazard ratio, 1.87; 95% confidence interval, 1.15-3.05; p = 0.012). CONCLUSIONS: Cigarette smoking dosage of ≥ 30 pack-years is an independent negative predictive factor of EGFR-TKI treatment outcome in lung adenocarcinoma patients with activating EGFR mutations.
OBJECTIVES: The aim of this study is to evaluate the predictive impact of cigarette smoking on treatment outcomes of EGFR-tyrosine kinase inhibitors (TKIs) in lung adenocarcinomapatients with activating EGFR mutations. METHODS: We retrospectively analyzed 222 consecutive recurrent or unresectable lung adenocarcinomapatients who harbored activating EGFR mutations (exon 19 deletion or exon 21 L858R) and had received gefitinib or erlotinib. Detailed smoking histories were obtained from all patients according to a standard protocol. RESULTS: Of 222 EGFR-mutated patients, 65.3% were never-smokers, 19.8% were smokers with < 30 pack-years, and 14.9% were smokers with ≥ 30 pack-years smoking dosage. The disease control rate (DCR) and objective response rate (ORR) of smokers with ≥ 30 pack-years were significantly lower than never-smokers and smokers with < 30 pack-years (DCR, 78.8% vs. 93.1%, p = 0.016; ORR, 45.5% vs. 62.4%, p = 0.020). Smokers with ≥ 30 pack-years showed significantly shorter PFS than never-smokers (6.4 vs. 11.8 months, p = 0.001) and smokers with < 30 pack-years (6.4 vs. 11.4 months, p = 0.033), as well as shorter overall survival from the time of metastatic diagnosis than never-smokers (33.6 vs. 46.2 months, p = 0.003). There was no survival difference between smokers with < 30 pack-year and never smokers. In the multivariate analysis adjusted for age, sex, performance status, initial stage, and line of EGFR-TKI, the presence of smoking dosage ≥ 30 pack-years was an independent predictive factor for the disease progression to EGFR-TKIs (hazard ratio, 1.87; 95% confidence interval, 1.15-3.05; p = 0.012). CONCLUSIONS: Cigarette smoking dosage of ≥ 30 pack-years is an independent negative predictive factor of EGFR-TKI treatment outcome in lung adenocarcinomapatients with activating EGFR mutations.