Erlotinib versus gemcitabine/cisplatin in Chinese patients with EGFR mutation-positive advanced non-small-cell lung cancer: Crossover extension and post-hoc analysis of the ENSURE study.
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.
['Wu|Yi-Long|YL|', 'Zhou|Caicun|C|', 'Lu|Shun|S|', 'Qin|Shukui|S|', 'Pan|Hongming|H|', 'Wu|Gang|G|', 'Cheng|Ying|Y|', 'Liu|Xiaoqing|X|', 'Han|Baohui|B|', 'Zhu|Yunzhong|Y|', 'Zhong|Zhaoyang|Z|', 'Huang|Cheng|C|', 'Chen|Lei|L|', 'Liang|Houjie|H|', 'Li|Enxiao|E|', 'Jiang|Guoliang|G|']
D000328:Adult D000368:Aged D000971:Antineoplastic Combined Chemotherapy Protocols D002289:Carcinoma, Non-Small-Cell Lung D002681:China D002945:Cisplatin D018592:Cross-Over Studies D003841:Deoxycytidine D066246:ErbB Receptors D000069347:Erlotinib Hydrochloride D005260:Female D005500:Follow-Up Studies D006801:Humans D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D009154:Mutation D009367:Neoplasm Staging D016019:Survival Analysis D016896:Treatment Outcome
Erlotinib EGFR Chemotherapy Asian Non small cell lung cancer