Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced‐stage nonsmall cell lung cancer

Abstract

BACKGROUND. Cetuximab, an immunoglobulin (Ig) G1 chimeric monoclonal antibody against the epidermal growth factor receptor, has demonstrated evidence of activity in nonsmall cell lung cancer (NSCLC). When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab has exhibited synergistic interaction in preclinical studies. Therefore, a phase 2 study was conducted to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. METHODS. Chemotherapy‐naïve patients aged ≥18 years with stage IIIB (with effusion) or stage IV NSCLC received cetuximab (at a dose of 400 mg/m2 on Day 1 and 250 mg/m2 on Days 8 and 15) plus docetaxel (at a dose of 75 mg/m2 on Day 1) and carboplatin (area under the concentration vs time curve [AUC] = 6 on Day 1) every 21 days for up to 6 cycles (graded according to the American Joint Committee on Cancer Staging System). Thereafter, patients without evidence of disease progression were continued on single‐agent cetuximab for a maximum of 1 year or until disease progression. The primary endpoint was response rate. RESULTS. Eighty patients were enrolled. The median number of cycles administered was 4 (range, 1‐6 cycles). The objective response rate was 15.2%, with a median progression‐free survival of 4.6 months and a median overall survival of 10.3 months. The salient grades 3 of 4 adverse events were neutropenia (30%), hypotension (3%), hypokalemia (4%), and hypomagnesemia (3%). Twenty‐five patients received single‐agent cetuximab (median duration, 12 weeks) and this was well tolerated. CONCLUSIONS. The results of this large, multicenter, phase 3 study indicate that the novel combination of cetuximab with docetaxel and carboplatin demonstrate modest anticancer activity for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile. Cancer 2008. © 2008 American Cancer Society.

Recent Advances Relating to the Clinical Application of Naked Monoclonal Antibodies in Solid Tumors

“…Also of note are the disappointing results of a phase I trial that evaluated the combination of cetuximab/paclitaxel in patients with MBC. In this study and because of prohibitive grade 3 rash combined with disappointing preliminary efficacy, the combination tested was not considered promising (27). Preoperative chemoradiotherapy with cetuximab, capecitabine, and weekly irinotecan has been shown in a phase I trial to be feasible and well tolerated in patients with locally advanced rectal cancer (28).…”

Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer

“…Cetuximab, a humanised monoclonal antibody that prevents ligand binding to the extracellular domain of EGFR, has shown encouraging results in NSCLC in combination with standard chemotherapy, in both the first-and second-line settings [79][80][81][82][83]. In the First-Line ErbituX in Lung Cancer (FLEX) study, a randomised, phase III study of cetuximab combined with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with EGFR immunohistochemistry (IHC)-positive advanced NSCLC, patients receiving cetuximab had statistically longer OS (primary end-point) than those receiving CV alone (11.3 versus 10.1 months; HR 0.871; p50.044).…”

Conclusion

“…The response rate was 14.5%, with a median PFS time of 4.7 months and a median overall survival time of 11 months. Twenty-five patients received maintenance therapy with single-agent cetuximab (median treatment duration was 12 weeks) and this was well tolerated [33].…”

“…The response rate was 14.5%, with a median PFS time of 4.7 months and a median overall survival time of 11 months. Twenty-five patients received maintenance therapy with single-agent cetuximab (median treatment duration was 12 weeks) and this was well tolerated [33].Cetuximab has also been studied in combination with gemcitabine-based doublets in a phase II trial enrolling previously untreated patients with stage IIIB/IV NSCLC irrespective of their EGFR status. Patients received cetuximab combined with either cisplatin plus gemcitabine or carboplatin plus gemcitabine.…”