A phase 2 study of cetuximab in combination with docetaxel in chemotherapy‐refractory/resistant patients with advanced nonsmall cell lung cancer

Abstract

Background Cetuximab in combination with docetaxel was examined in chemotherapy-refractory/resistant patients with advanced nonsmall-cell lung cancer (NSCLC) to determine response rate, survival, safety, and pharmacokinetics (PK). Methods Patients had evidence of epidermal growth factor receptor (EGFR) expression (≥1 +) and tumor progression during or disease recurrence within 3 months after chemotherapy. Cetuximab was administered weekly (400 mg/m2 initial; 250 mg/m2 thereafter). Docetaxel was administered every 3 weeks (75 mg/m2). A response in 3 of the first 21 patients was required to continue accrual to the target sample size of 50 patients. Results Confirmed responses included 1 complete response (1.8%), 10 partial responses (18.2%), and 20 with stable disease (36.4%). The response rate was 20% (95% confidence interval [CI], 10.4% to 33.0%) and median time to disease progression was 104 days. There were no differences in PK parameters of docetaxel alone or with cetuximab. The most common grade 3 of 4 adverse events were leukopenia (27.3%) and acne (21.8%). Four patients (7.3%) discontinued due to allergic reaction. The median overall survival (OS) was 7.5 months with a 1-year survival of 35%. Conclusions Cetuximab in combination with docetaxel was well tolerated. The response rate supports more definitive evaluation of this combination in the second-line setting.

The overexpression of ERCC-1 is involved in the resistance of lung cancer cells to cetuximab combined with DDP

“…21 In addition, other trials preliminarily showed that either cetuximab combined with carboplatin and taxane or cetuximab combined with gemcitabine produced modestly clinical benefit. [22][23][24][25][26][27] Most target therapeutics show superiority just in a subset of patients (the preponderant population) and the preselection of patients becomes a key factor in the clinical setting. 28 So, it is necessary to find the preponderant population among NSCLC for the combination of cetuximab and DDP, just as the ones with wild type of K-ras gene among mCRC for the combination of cetuximab and CPT-11.…”

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).…”

Standing the test of time in Europe? Gefitinib in the treatment of non-small-cell lung cancer

“…Cetuximab was investigated in pretreated NSCLCs in a phase II trial in addition to docetaxel 75 mg/m 2 in patients who had progressed on prior platinum chemotherapy; a median survival time of 7.5 months was reported and a 28% response rate. 35 A phase II trial was conducted with cetiximab as monotherapy in pretreated NSCLCs, with a median survival of 8.1 months and 1 year survival of 41%. 36 Cetuximab's use as a first line therapy was investigated in three phase II trials, in addition to platinum-containing chemotherapy, as first line treatment in EGFR mutation positive patients.…”