Keigo Kobayashi1, Kenzo Soejima2, Koichi Fukunaga2, Yasushi Shintani3, Ikuo Sekine4, Takehito Shukuya5, Koichi Takayama6, Akira Inoue7, Isamu Okamoto8, Katsuyuki Kiura9, Kazuhisa Takahashi5, Nobuyuki Yamamoto10, Yuichi Takiguchi11, Etsuo Miyaoka12, Meinoshin Okumura13, Ichiro Yoshino14. 1. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan. Electronic address: keigokbys@gmail.com. 2. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan. 3. Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. 4. Department of Medical Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 5. Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. 6. Department of Respirology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 7. Department of Palliative Medicine, Tohoku University School of Medicine, Miyagi, Japan. 8. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu, Japan. 9. Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan. 10. Third Department of Internal Medicine, Wakayama Medical University Hospital, Wakayama, Japan. 11. Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan. 12. Department of Mathematics, Science University of Tokyo, Tokyo, Japan. 13. Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Osaka, Japan. 14. Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Abstract
INTRODUCTION: The efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-adenocarcinoma (ADC) non-small cell lung cancer patients is not well established. Herein, we investigated key prognostic factors influencing the efficacy of EGFR-TKIs in these patients. METHODS: A total of 12,320 lung cancer patients pathologically diagnosed in 2012 at teaching hospitals in Japan were retrospectively selected. The follow-up survey was closed in 2016. RESULTS: EGFR-mutated non-ADC patients were more prone to malignant pleural effusion (MPE) and distant metastasis than ADC patients (P = 0.071 and 0.022, respectively). EGFR-mutated ADC patients were likely to have a longer median overall survival (OS) than non-ADC patients [hazard ratio (HR) 1.3 (95 % CI, 0.97-1.8, P = 0.072)-29.5 months (95 % CI, 27.9-31.1 months) versus 19.5 months (95 % CI, 10.8-28.2 months) (P = 0.068)]. There was no significant difference in median OS between EGFR-positive ADC and non-ADC patients receiving treatment with first-generation EGFR-TKI. Among EGFR-positive non-ADC patients, the median OS was significantly longer for patients receiving EGFR-TKI treatment than for those who did not [HR 4.5 (95 % CI, 2.1-9.8, P < 0.001)-25.5 months (95 % CI, 8.1-42.9 months) versus 7.5 months (95 % CI, 3.4-11.6 months) (P < 0.001)]. While there was no significant difference in the median OS for ADC patients with either 19 del or L858R mutations, the median OS was significantly longer for EGFR-mutated non-ADC patients with 19 del than for those with L858R mutation (HR 3.2 [95 % CI, 1.5-6.9, P = 0.004]; it was not reached for 19 del and was 15.5 months for L858R [95 % CI, 6.6-24.4 months], P = 0.002). DISCUSSION: EGFR-mutated non-ADC patients were more prone to MPE and distant metastasis. Both ADC and EGFR del19-positive non-ADC patients can benefit from EGFR-TKI treatment, whereas EGFR L858R-positive non-ADC patients might require different therapeutic options.
INTRODUCTION: The efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-adenocarcinoma (ADC) non-small cell lung cancer patients is not well established. Herein, we investigated key prognostic factors influencing the efficacy of EGFR-TKIs in these patients. METHODS: A total of 12,320 lung cancer patients pathologically diagnosed in 2012 at teaching hospitals in Japan were retrospectively selected. The follow-up survey was closed in 2016. RESULTS: EGFR-mutated non-ADC patients were more prone to malignant pleural effusion (MPE) and distant metastasis than ADC patients (P = 0.071 and 0.022, respectively). EGFR-mutated ADC patients were likely to have a longer median overall survival (OS) than non-ADC patients [hazard ratio (HR) 1.3 (95 % CI, 0.97-1.8, P = 0.072)-29.5 months (95 % CI, 27.9-31.1 months) versus 19.5 months (95 % CI, 10.8-28.2 months) (P = 0.068)]. There was no significant difference in median OS between EGFR-positive ADC and non-ADC patients receiving treatment with first-generation EGFR-TKI. Among EGFR-positive non-ADC patients, the median OS was significantly longer for patients receiving EGFR-TKI treatment than for those who did not [HR 4.5 (95 % CI, 2.1-9.8, P < 0.001)-25.5 months (95 % CI, 8.1-42.9 months) versus 7.5 months (95 % CI, 3.4-11.6 months) (P < 0.001)]. While there was no significant difference in the median OS for ADC patients with either 19 del or L858R mutations, the median OS was significantly longer for EGFR-mutated non-ADC patients with 19 del than for those with L858R mutation (HR 3.2 [95 % CI, 1.5-6.9, P = 0.004]; it was not reached for 19 del and was 15.5 months for L858R [95 % CI, 6.6-24.4 months], P = 0.002). DISCUSSION: EGFR-mutated non-ADC patients were more prone to MPE and distant metastasis. Both ADC and EGFR del19-positive non-ADC patients can benefit from EGFR-TKI treatment, whereas EGFR L858R-positive non-ADC patients might require different therapeutic options.