CTONG1103: Final overall survival analysis of the randomized phase 2 trial of erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non–small cell lung cancer.

8502 Background: Median Overall survival (mOS) of stage IIIA resected NSCLC was 59.4 months (m) in CTONG 1104 adj gefitinib and 26.2m in SAKK neoadjuvant chemo trial. EMERGING-CTONG1103 showed neo-adjuvant/adjuvant erlotinib treatment significantly improved progression-free survival (PFS) vs standard doublet chemotherapy in patients (pts) with epidermal growth factor receptor ( EGFR) mutation-positive resectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Here, we present the final overall survival (OS) results from the study. Methods: This was a multicenter (17 centers in China) phase II randomized controlled trial of erlotinib（E）versus gemcitabine plus cisplatin (GC) as neoadjuvant/adjuvant therapy in pts with stage IIIA-N2 NSCLC with EGFR mutations in exon 19 or 21. From Dec 2011 to Dec. 2017, 386 pts sites were screened and 72 pts were randomly assigned to neoadjuvant/adjuvant E arm (N = 37) or GC arm(N = 35). Patients received erlotinib 150 mg/d (neoadjuvant therapy, 42 days; adjuvant therapy, up to 12 months) or gemcitabine 1,250 mg/m2 plus cisplatin 75 mg/m2 (neoadjuvant therapy, two cycles; adjuvant therapy, up to two cycles). Assessments were performed at 6 weeks and every 3 months postoperative. The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; secondary end points were pathologic complete response, downstaging rates of pathological lymph nodes, PFS, OS, safety, and tolerability. Data cut-off date was January, 29 2021. Results: With a median follow-up of 62.5 months, the median OS was 42.2months based on 47 (65.3%) events in ITT whole population. The mOS was 42.2m in E and 36.9m in GC (HR 0.83, 95%CI 0.47-1.47, p = 0.513). The 3-,5-year OS rate were 58.6%, 40.8% in E and 55.9%, 27.6% in GC respectively (p3-y = 0.819, p5-y = 0.252). All predefined subgroups including age, gender, EGFR mutation type had no significant difference in statistics between two arms. Subsequent treatments (ST) especially targeted therapy contributed most to OS (HR = 0.35,95% CI 0.18- 0.70). Median OS of pts receiving ST was 45.8m (n = 38), 34.6m in other treatment (n = 12), 24.6m in without ST (n = 15). For E mOS were 46.4 (n = 15; target therapy), 42.2m (n = 8; other) and 24.6m (n = 9; without, p = 0.021), for GC 42.6 (n = 23; target therapy), 30.1m (n = 4;other) and 24.6m(n = 6; without, p = 0.130). The RR was 53.3%, DCR 93.3%, mPFS 10.9m and mPPS 21.9m for patients with rechallenged EGFR TKI in E arm (n = 15). No novel unexpected SAE was observed during follow up. Conclusion: Erlotinib as neoadjuvant/adjuvant therapy for resected N2 NSCLC was feasibility and had a promising OS. The PFS survival advantage of E did not translate to OS difference in EMERGING trial (NCT01407822). Clinical trial information: NCT01407822.