Yi-Long Wu1, Caicun Zhou2, Shun Lu3, Shukui Qin4, Hongming Pan5, Gang Wu6, Ying Cheng7, Xiaoqing Liu8, Baohui Han3, Yunzhong Zhu9, Zhaoyang Zhong10, Cheng Huang11, Lei Chen12, Houjie Liang13, Enxiao Li14, Guoliang Jiang15. 1. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn. 2. Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 3. Department of Lung Cancer, Shanghai Chest Hospital, Shanghai, China. 4. Nanjing Bayi Hospital, Nanjing, China. 5. Sir Run Shaw Hospital Affiliated to Zhejiang University, Hangzhou, China. 6. Cancer Center of Union Hospital, Tongji Medical College, Huzhong University of Science and Technology, Wuhan, China. 7. Jilin Cancer Hospital, Changchun, China. 8. PLA 307 Hospital, Beijing, China. 9. Department of Lung Cancer, Beijing, China Tuberculosis and Thoracic Tumor Research Institute, Beijing, China. 10. Cancer Centre, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China. 11. Fujian Provincial Tumor Hospital, Fujian, China. 12. Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China. 13. Affiliated Xinan Hospital of Third Military Medical University, Chongqing, China. 14. First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China. 15. Fudan University Shanghai Cancer Center, Shanghai, China.
Abstract
OBJECTIVES: Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC. MATERIALS AND METHODS: Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD). Those with PD on first-line erlotinib (n = 24) received gemcitabine/cisplatin while those who failed first-line chemotherapy (n = 21) received erlotinib until second-line PD. The primary endpoint was PFS in the crossover subpopulation. Post-hoc analysis of survival outcomes was also measured for the overall population of 175 Chinese patients. RESULTS: Among patients who crossed over at progression, PFS was comparable between those who received second-line erlotinib and those who received second-line chemotherapy (median, 26.3 months and 23.4 months, respectively; P = 0.529). Regardless of the sequence in which the therapies were administered, patients in the crossover treatment subgroup benefited from either second-line therapy after progression with a median overall survival of 51.6 months versus 23.0 months achieved among patients in the non-crossover treatment subgroup. Post-hoc biomarker analyses of Kaplan-Meier survival curves and Cox regression showed that survival benefits with either treatment sequence were similar between patients with circulating free DNA EGFR mutations in exons 19 and 21; however, those with undetectable mutations achieved significantly greater survival benefits. CONCLUSION: In advanced EGFR mutation-positive NSCLC, first-line erlotinib followed by chemotherapy at progression demonstrated comparable PFS benefit with the inverse treatment sequence, irrespective of mutation subtype. Utilizing both EGFR-TKIs and chemotherapy, irrespective of the sequence, maximizes survival benefits for patients.
OBJECTIVES: Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC. MATERIALS AND METHODS: Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD). Those with PD on first-line erlotinib (n = 24) received gemcitabine/cisplatin while those who failed first-line chemotherapy (n = 21) received erlotinib until second-line PD. The primary endpoint was PFS in the crossover subpopulation. Post-hoc analysis of survival outcomes was also measured for the overall population of 175 Chinese patients. RESULTS: Among patients who crossed over at progression, PFS was comparable between those who received second-line erlotinib and those who received second-line chemotherapy (median, 26.3 months and 23.4 months, respectively; P = 0.529). Regardless of the sequence in which the therapies were administered, patients in the crossover treatment subgroup benefited from either second-line therapy after progression with a median overall survival of 51.6 months versus 23.0 months achieved among patients in the non-crossover treatment subgroup. Post-hoc biomarker analyses of Kaplan-Meier survival curves and Cox regression showed that survival benefits with either treatment sequence were similar between patients with circulating free DNA EGFR mutations in exons 19 and 21; however, those with undetectable mutations achieved significantly greater survival benefits. CONCLUSION: In advanced EGFR mutation-positive NSCLC, first-line erlotinib followed by chemotherapy at progression demonstrated comparable PFS benefit with the inverse treatment sequence, irrespective of mutation subtype. Utilizing both EGFR-TKIs and chemotherapy, irrespective of the sequence, maximizes survival benefits for patients.