A phase II trial of adding cetuximab to cisplatin and gemcitabine as first-line therapy in advanced non-small cell lung cancer (NSCLC)

Abstract

e19043 Background: Phase II and III studies have demonstrated that the EGFR-antibody, cetuximab (Erbitux), improves efficacy parameters when added to a platinum-based chemotherapy in the 1st-line treatment of patients with advanced NSCLC. This study assessed the efficacy and tolerability of cetuximab in combination with cisplatin and gemcitabine in this setting. Methods: Patients in this multicenter, single-arm, phase II Portuguese study received cetuximab (400 mg/m2 initial dose then 250 mg/m2 weekly) in combination with cisplatin (40 mg/m2) and gemcitabine (1,200 mg/m2) for 6 cycles (21 days). Main eligibility criteria included metastatic NSCLC of any histological subtype, ECOG PS 0/1, and measurable disease. Patients with brain metastases were excluded. The primary endpoint was the overall response rate (ORR) during treatment, according to RECIST criteria. Secondary endpoints included time to progression (TTP), overall survival, and adverse events. Statistical analyses were performed for the intention to treat (ITT) and per protocol populations. ORRs and the corresponding 95% confidence intervals (CIs) were estimated and Kaplan-Meier curves were computed for TTP. Results: A total of 48 patients were enrolled between December 2006 and March 2008. Seventy five percent of the patients were men and the median age was 62.5 years (range 34–75). Median TTP was 5.0 months (95% CI 3.9–6.1 months). Best ORR were 35.4% (95% CI 22.2–50.5%) and 38.1% (95% CI 23.6–54.4%) for the ITT and PP populations, respectively. No differences in response rates were observed when EGFR status (as determined by FISH and immunohistochemistry) was taken into consideration. Ninety-six grade III/V adverse events were reported; the most common were neutropenia and thrombocytopenia (36 and 18 events, respectively). Conclusions: Adding cetuximab to cisplatin and gemcitabine demonstrated high efficacy (ORR and TTP) with acceptable toxicities in a nonselected population of patients in 1st-line treatment of NSCLC. No significant financial relationships to disclose.