PURPOSE To evaluate the efficacy of cetuximab plus taxane/carboplatin (TC) as first-line treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS This multicenter, open-label, phase III study enrolled 676 chemotherapy-naïve patients with stage IIIB (pleural effusion) or IV NSCLC, without restrictions by histology or epidermal growth factor receptor expression. Patients were randomly assigned to cetuximab/TC or TC. TC consisted of paclitaxel (225 mg/m(2)) or docetaxel (75 mg/m(2)), at the investigator's discretion, and carboplatin (area under the curve = 6) on day 1 every 3 weeks for < or = six cycles; cetuximab (400 mg/m(2) on day 1, 250 mg/m(2) weekly) was administered until progression or unacceptable toxicity. The primary end point was progression-free survival assessed by independent radiologic review committee (PFS-IRRC); overall response rate (ORR), overall survival (OS), quality of life (QoL), and safety were key secondary end points. PFS and ORR assessed by investigators were also evaluated. Results Median PFS-IRRC was 4.40 months with cetuximab/TC versus 4.24 months with TC (hazard ratio [HR] = 0.902; 95% CI, 0.761 to 1.069; P = .236). Median OS was 9.69 months with cetuximab/TC versus 8.38 months with TC (HR = 0.890; 95% CI, 0.754 to 1.051; P = .169). ORR-IRRC was 25.7% with cetuximab/TC versus 17.2% with TC (P = .007). The safety profile of this combination was manageable and consistent with its individual components. CONCLUSION The addition of cetuximab to TC did not significantly improve the primary end point, PFS-IRRC. There was significant improvement in ORR by IRRC. The difference in OS favored cetuximab but did not reach statistical significance.

The addition of PF-3512676 to taxane plus platinum chemotherapy for first-line treatment of NSCLC improves objective response and may improve survival. Confirmatory phase III trials are ongoing.

Grade 3/4 AEs occurred in 40.6% (gefitinib) and 81.6% (docetaxel) of patients. The incidence of interstitial lung disease (ILD) was 5.7% (n=14) and 2.9% (n=7) with gefitinib and docetaxel, respectively. There were four deaths due to AEs in the gefitinib arm (three possibly treatment-related due to ILD; one due to pneumonia that was not considered treatment-related), and none in the docetaxel arm. Biomarker data will also be reported. Conclusions: Non-inferiority in overall survival between gefitinib and docetaxel was not demonstrated according to predefined criteria. However, there was no statistically significant difference in survival between the two groups. Imbalances in the proportion and type of post-study treatments in both arms have complicated interpretation of survival results. The secondary endpoints are largely unaffected by subsequent therapy and provide further evidence of the clinical efficacy of gefitinib in Japanese patients. AEs were consistent with those previously observed for both treatments.