Cisplatin-based doublet chemotherapy as neoadjuvant treatment for IIIA-N2 non-small cell lung cancer (NSCLC) give patients 5% survival benefit. EGFR-TKIs have been proved to prolong PFS of advanced EGFR-mutant NSCLC. CTONG1104 trial shown adjuvant gefitinib could improve 10 months (disease free survival) DFS than chemotherapy in N1/N2 resected NSCLC. It raises the possibility that EGFR-TKIs may play a beneficial role in the neoadjuvant setting. We conducted this randomized trial to compare the efficacy of erlotinib (E) and gemcitabine plus cisplatin (GC) as neoadjuvant/adjuvant treatment.
Eligible patients with N2 disease were randomly assigned in 1:1 ratio to E group for 42 days as neoadjuvant therapy and then for 12 months after surgery or GC group for 2 cycles neoadjuvant chemotherapy and 2 cycles after complete resection. The primary endpoint is objective response rate (ORR). secondary endpoints included downstaging rates of pathological lymph nodes, pathological complete response (pCR), progression-free survival (PFS), overall survival (OS), safety, and tolerability.
A total of 386 patients from 17 centers were screened, 72 were randomized and included in the intention-to-treat population. The ORR for neoadjuvant E versus GC was 54.1% (95% CI, 37.2% to 70.9%) vs 34.3% (95% CI, 17.7% to 50.8%) (OR 2.26; 95% CI, 0·87–5.84; p=0·092). After neoadjuvant therapy, 31 patients (83·8%) in the E group and 24 (68·6%) in the GC group underwent surgery. Overall, lymph node downstaging occurred in 13% in the E and 4·2% in the GC group. The major pathological response (MPR) occurred in 3 of 28 patients (10.7%) in the E and no MPR (0/22) in the GC group. Median PFS was significantly longer with E (21·5 months; 95% CI, 19·3–23·6) versus GC (11·9 months; 95% CI, 9·1–14·7; HR 0·42; 95% CI, 0·23–0·76; p=0·003), whereas OS data was immature. The incidence of grade 3/4 toxicities was lower in the E group (0%) than that in the GC group (29·4%). No unexpected AEs were found.
Neoadjuvant/adjuvant erlotinib improved ORR, and significantly prolonged PFS compared with GC chemotherapy in patients with stage IIIA-N2 EGFR mutation NSCLC.
Clinical trial identification