Gee-Chen Chang1, Chien-Hua Tseng2, Kuo-Hsuan Hsu3, Chong-Jen Yu4, Cheng-Ta Yang5, Kun-Chieh Chen6, Tsung-Ying Yang7, Jeng-Sen Tseng7, Chien-Ying Liu4, Wei-Yu Liao5, Te-Chun Hsia8, Chih-Yen Tu9, Meng-Chih Lin10, Ying-Huang Tsai11, Meng-Jer Hsieh12, Wen-Shuo Wu13, Yuh-Min Chen14. 1. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, and Faculty of Medicine, School of Medicine, National Yang-Ming University, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: august@vghtc.gov.tw. 2. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan; Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. 3. Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. 4. Department of Internal Medicine, National Taiwan University Hospital, Taiwan. 5. Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 6. Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. 7. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, and Faculty of Medicine, School of Medicine, National Yang-Ming University, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. 8. Department of Respiratory Therapy, China Medical University and Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. 9. Division of Pulmonary and Critical Care, China Medical University Hospital, Taichung, Taiwan. 10. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. 11. Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan. 12. Department of Pulmonary and Critical Care Medicine Chiayi Chang-Gung Memorial Hospital, Taiwan. 13. Department of Chest Medicine, Taipei AVeterans General Hospital, School of Medicine, National Yang-Ming Medical University, and School of Medicine, Taipei Medical University, Taipei, Taiwan. 14. Department of Chest Medicine, Taipei AVeterans General Hospital, School of Medicine, National Yang-Ming Medical University, and School of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: ymchen@vghtpe.gov.tw.
Abstract
BACKGROUND: Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. MATERIALS AND METHODS: This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled. The objectives were to assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of EGFR TKI switched retreatment. RESULTS: In total, 205 patients were enrolled, with a median age of 61.8 years (range 31.4-92.9). There was a larger proportion of females (62.9%) than males, and more never-smokers (73.2%) than ever-smokers. In the initial EGFR-TKI administration, 57.6% of patients showed a complete response (CR) or partial response (PR), and 34.6% had stable disease (SD); in the second-line chemotherapy, 13.7% had PR, and 58.0% had SD; in the EGFR-TKI retreatment, 7.3% had PR, and 37.1% had SD. The median PFS of first-line EGFR-TKI was 8.0 months (95% CI 7.3-8.2), and retreatment EGFR-TKI was 4.1 months (95% CI 2.7-4.6). The median OS since the start of the first-line EGFR-TKI therapy was 35.9 months (95% CI 28.8-50.9), and since the start of EGFR-TKI retreatment was 12.6 months (95% CI 10.4-20.9). In the univariable and multivariable regression analysis of factors associated with PFS of EGFR-TKI retreatment, time interval between the two EGFR TKIs equal to or more than 7 months was statistically significant (HR=0.62, 95% CI 0.44-0.86; HR=0.6, 95% CI 0.43-0.86), both p<0.01. Females with exon 21 mutation also showed a significant difference between the two groups (HR=0.51, 95% CI 0.30-0.86; HR=0.52 (0.31-0.88), both p<0.05). CONCLUSIONS: EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLC patients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation. Copyright Â
BACKGROUND: Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. MATERIALS AND METHODS: This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled. The objectives were to assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of EGFR TKI switched retreatment. RESULTS: In total, 205 patients were enrolled, with a median age of 61.8 years (range 31.4-92.9). There was a larger proportion of females (62.9%) than males, and more never-smokers (73.2%) than ever-smokers. In the initial EGFR-TKI administration, 57.6% of patients showed a complete response (CR) or partial response (PR), and 34.6% had stable disease (SD); in the second-line chemotherapy, 13.7% had PR, and 58.0% had SD; in the EGFR-TKI retreatment, 7.3% had PR, and 37.1% had SD. The median PFS of first-line EGFR-TKI was 8.0 months (95% CI 7.3-8.2), and retreatment EGFR-TKI was 4.1 months (95% CI 2.7-4.6). The median OS since the start of the first-line EGFR-TKI therapy was 35.9 months (95% CI 28.8-50.9), and since the start of EGFR-TKI retreatment was 12.6 months (95% CI 10.4-20.9). In the univariable and multivariable regression analysis of factors associated with PFS of EGFR-TKI retreatment, time interval between the two EGFR TKIs equal to or more than 7 months was statistically significant (HR=0.62, 95% CI 0.44-0.86; HR=0.6, 95% CI 0.43-0.86), both p<0.01. Females with exon 21 mutation also showed a significant difference between the two groups (HR=0.51, 95% CI 0.30-0.86; HR=0.52 (0.31-0.88), both p<0.05). CONCLUSIONS:EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLCpatients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation. Copyright Â
Authors: Zofia Piotrowska; Mehlika Hazar-Rethinam; Coleen Rizzo; Brandon Nadres; Emily E Van Seventer; Heather A Shahzade; Inga T Lennes; Anthony J Iafrate; Dora Dias-Santagata; Ignaty Leshchiner; Nicholas A Jessop; Haichuan Hu; Subba R Digumarthy; Rebecca J Nagy; Richard B Lanman; Susan Moody; Matthew J Niederst; Jeffrey A Engelman; Aaron N Hata; Ryan B Corcoran; Lecia V Sequist Journal: JCO Precis Oncol Date: 2018-07-16
Authors: Meng Yang; Umit Topaloglu; W Jeffrey Petty; Matthew Pagni; Kristie L Foley; Stefan C Grant; Mac Robinson; Rhonda L Bitting; Alexandra Thomas; Angela T Alistar; Rodwige J Desnoyers; Michael Goodman; Carol Albright; Mercedes Porosnicu; Mihaela Vatca; Shadi A Qasem; Barry DeYoung; Ville Kytola; Matti Nykter; Kexin Chen; Edward A Levine; Edgar D Staren; Ralph B D'Agostino; Robin M Petro; William Blackstock; Bayard L Powell; Edward Abraham; Boris Pasche; Wei Zhang Journal: J Hematol Oncol Date: 2017-05-04 Impact factor: 17.388