Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage III non-small cell lung cancer: a preliminary report.

OBJECTIVE: In recent years, the combination of cetuximab and chemoradiotherapy (CRT) has been used to treat stage III non-small cell lung cancer (NSCLC); however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT (CCRT) in Chinese patients with stage III NSCLC. METHODS: Eligibility criteria were Zubrod performance status (PS) 0-1, forced expiratory volume in 1 second (FEV1) ≥1.2 L and adequate organ function. Enrolled patients received weekly cetuximab (initial dose of 400 mg/m(2) on day 1 of week 1 and a maintenance dose of 250 mg/m(2) on week 2 to the end of CCRT) with cisplatin/vinorelbine (NP) chemotherapy (every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy (TRT) (60-66 Gy/2 Gy). The primary endpoints were toxicity and feasibility. All patients received positron emission tomography-computerized tomography (PET-CT) scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node-metastasis (TNM) stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. RESULTS: Seventeen patients were enrolled and 16 completed the full regime. The overall response rate (ORR) was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval (CI): 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% (95% CI, 60.6-96.9%) and 58.8% (95% CI, 60.6-77.8%), respectively. Three patients remain progression-free to date, and the median progression-free survival (PFS) was 13.5 months (95% CI, 6.8-20.2 months). No treatment-related death occurred; however, 76% of the patients experienced grade 3+ adverse events (AEs), including nausea/vomiting, intestinal obstruction, and esophagitis (<6%), while other AEs were mostly of hematological nature (71%). The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL (P=0.027), SUV-T (P=0.025), and PS (P=0.006) as potential survival predictors, with a hazard ratio (HR) of 3.4, 3.7, and 9.9, respectively. CONCLUSIONS: The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by (18)F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.