Baohui Han, Liwen Xiong, JiayuanSun, Rong Li, Yuqing Lou, Yanwei Zhang, Aiqing Gu, LiyanJiang, Jianxin Shi, Wentao Fang, Heng Zhao

Lung Cancer, Shanghai Chest Hospital affiliated toShanghai Jiaotong University

Background: Concurrentchemoradiation therapy or induction chemotherapy plus surgery were consideredas standard treatment to non-small-cell lung cancer (NSCLC) in stage IIIA-N2, butthe side effect became the obstacle for most patients to be treated and causepoor clinical outcome. We aimed to assess the benefit and tolerability ofneoadjuvant erlotinib in NSCLC staging IIIA-N2 patients with activating EGFRmutation. 

Method: Previouslyuntreated patients with endobronchial ultrasound confirmed stage IIIA-N2 NSCLCwith activating EGFR mutation in exon 19 or 21 were recruited into the study.All enrolled patients were treated with erlotinib 150mg orally per day for 56days for neoadjuvant period. Only patients who got benefits from erlotinibtreatment and were resectable would receive surgery. The primary endpoint isradical resection rate. The secondary endpoints included pathological completeresponse rate (pCR), objective response rate (ORR), disease free survival(DFS), overall survival (OS), safety profile, quality of life (QoL), andexplorative biomarkers. This study was registered in clinicaltrials.gov(NCT01217619). We confirmed the EGFR mutation status after the end of patients'recruitment. 

Result: From July 2011 to June 2014, total 155 patientswere screened and 25 patients were enrolled into the study. After confirm theEGFR mutation status, 21 patients (9m/12f, median age 59 yrs) were comply withthe requirements of this clinical trial and enter data analysis. Afterneoadjuvant erlotinib treatment, 38.1% (8/21) patients had partial response,47.6% (10/21) at stable disease and 14.3% (3/21) at progression of diseasebefore surgery. The ORR was 38.1% (8/21) and DCR was 85.7% (18/21). Sixteenpatients underwent resection surgery, in which fifteen patients (93.8%, 15/16)had R0 resection and the radical resection rate was 71.4% (15/21) in ITTpopulation. Radical resection rate was 93.8% in total 16 resected patients. Therewere 4 patients downstage to T0-3N0M0 including 1 patient got CR afterneoadjuvant therapy, which was demonstrated by the postopoerative pathology.The median DFS for surgery patients was 11.4 months. The median follow upperiod is 13.4 months and the OS data is still not matured currently. Mostpatients were consistent on EGFR mutation before and after the surgery exceptthree patients with exon 19 deletion turn to EGFR wild type after the surgery.No post-surgery infection was found. Seven patients (28.6%, 6/21) had rash andone patient (4.8%, 1/21) had diarrhea after erlotinib treatment. The patientswho got benefit from erlotinib have the lowest CEA level while those who didnot benefit from erlotinib (the patients did not receive surgery) have thehighest CEA level. 

Conclusion: Erlotinib as neoadjuvant therapy is apromising treatment for EGFR mutant IIIA-N2 NSCLC patients with tolerabletoxicity.

Key Words: NSCLC