Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099.

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.

Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study.

BACKGROUND: The activity and safety of vinflunine was evaluated in patients with locally advanced or metastatic urothelial carcinoma (UC) who developed disease progression within 12 months of platinum-containing chemotherapy. METHODS: Patients with UC were eligible if they received a prior platinum-based regimen in the neoadjuvant/adjuvant setting or as first-line treatment for advanced/metastatic disease and had developed disease progression within 12 months. Vinflunine was administered intravenously every 3 weeks. Patients with Karnofsky performance status of 80 or 90, impaired renal function, prior pelvic irradiation, or age>or=75 years received an initial dose of 280 mg/m2, which was escalated to 320 mg/m2 in Cycle 2 if well tolerated. All other patients received an initial dose of 320 mg/m2. The primary endpoint was response rate defined by an independent response review committee (IRRC). RESULTS: Per the IRRC, 22 patients achieved a partial response, with a response rate of 15% (95% confidence interval, 9%-21%) with a median duration of response of 6.0 months. Sixty-four (42%) patients had stable disease. The median progression-free survival was 2.8 months, and the median overall survival was 8.2 months. Myelosuppression was the most frequent adverse event, with grade 3 of 4 (adverse events were evaluated according to the National Cancer Institute Common Toxicity Criteria [version 2.0] guidelines) neutropenia reported in 58% of the patients. Grade 3 of 4 febrile neutropenia occurred in 10 (7%) patients. Nonhematologic treatment-related events (grade 3 of 4) were generally manageable and included constipation (17%), asthenia/fatigue (13%), ileus (5%), and abdominal pain (5%). No cumulative toxicity was observed. CONCLUSIONS: Vinflunine demonstrates moderate activity in patients with platinum-pretreated UC. Toxicity is manageable and noncumulative.

Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer.

PURPOSE: To evaluate the efficacy of cetuximab added to first-line gemcitabine/platinum in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In this noncomparative, randomized trial, chemotherapy-naïve patients with recurrent/metastatic NSCLC (stage IV or stage IIIB with malignant pleural effusion) were eligible. Patients received cisplatin (75 mg/m2 i.v., every 3 weeks) or carboplatin (area under the concentration-versus-time curve of 5 intravenously [i.v.], every 3 weeks), and gemcitabine (1,250 or 1,000 mg/m2 i.v., days 1 and 8) plus cetuximab (400 mg/m2 i.v. day 1, followed by 250 mg/m2 weekly), in arm A, or chemotherapy alone, in arm B. Response rate was the primary end point; safety, progression-free survival, and overall survival were secondary end points. RESULTS: Sixty-five patients were randomly assigned to arm A and 66 to arm B. Partial responses were observed in 18 patients (27.7%; 95% CI, 17.3 to 40.2) in arm A and 12 (18.2%; 95% CI, 9.8 to 29.6) in arm B. Median progression-free survival was 5.09 months for arm A (95% CI, 4.17 to 5.98) and 4.21 months (95% CI, 3.81 to 5.49) in arm B. Median overall survival was 11.99 months (95% CI, 8.80 to 15.18) and 9.26 months (95% CI, 7.43 to 11.79) in arms A and B, respectively. Overall toxicity was acceptable and consistent with the profiles of the individual agents. CONCLUSION: First-line treatment with cetuximab plus gemcitabine/platinum is well tolerated and can be administered safely in patients with advanced NSCLC. Differences in response rate, progression-free survival, and overall survival suggest that the addition of cetuximab to platinum/gemcitabine may improve clinical outcomes. Larger studies are in progress to address this hypothesis.