Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial.

By R. Pirker, J. R. Pereira, A. Szczesna, J. von Pawel, M. Krzakowski, R. Ramlau, I. Vynnychenko, Keunchil Park, Chih-Teng Yu, V. Ganul and 8 more. The Lancet, 2009

1,399 citations recorded by the source corpus.

BACKGROUND Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer. METHODS In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (>or=18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m(2) intravenous infusion on day 1, and vinorelbine 25 mg/m(2) intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab-at a starting dose of 400 mg/m(2) intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m(2) over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00148798. FINDINGS Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11.3 months vs 10.1 months; hazard ratio for death 0.871 [95% CI 0.762-0.996]; p=0.044). The main cetuximab-related adverse event was acne-like rash (57 [10%] of 548, grade 3). INTERPRETATION Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer. FUNDING Merck KGaA.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/a69a745f80104f2b71b5881e1e2220cd5981b6fd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

1. William Pao
2. Bruce A. J. Ponder
3. K. Kerr
4. M. Hellmann
5. Ryuji Hamamoto

In Pulmonary and Respiratory Medicine

1. B. Hughes
2. B. Chan
3. William Pao

Citations in the corpus

• Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2018, background): “Of note, three studies, one employing bevacizumab and the other two using monoclonal antibodies against EGFR (cetuximab or necitumumab) administered concomitantly to ChT and further continued as monotherapy until disease progression, have demonstrated survival benefits; however, the specific role of”
• Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer (2011, background): “for some patients, engender a drive towards novel molecular-targeting agents [46-48].”
• Web-Based Survival Analysis Tool Tailored for Medical Research (KMplot): Development and Implementation (2021, critical): “Their main problem with the trial was the minimal overall survival benefit of only 12% and that only the exceptionally high sample number (N=1125) helped to reach a minimally significant P value of .04 [23].”
• American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. (2009, methodology): “In the First-Line Erbitux in Lung Cancer (FLEX) study (chemotherapy plus cetuximab v placebo), eligibility required that tumors contain at least one EGFR-positive cell as determined by IHC, a low threshold that allowed 85% of patients (1,442 of 1,688 patients) screened to be eligible.(96)”
• Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. (2015, background): “Two phase III studies, FLEX (52) and BMS099 (53) have examined the combination of cetuximab with platinum doublet chemotherapy in advanced NSCLC (Table 1).”