A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

P. Bossi, R. Miceli, L.D. Locati, D. Ferrari, S. Vecchio, G. Moretti, N. Denaro, F. Caponigro, M. Airoldi, C. Moro, E. Vaccher, A. Sponghini, A. Caldara, G. Rinaldi, F. Ferrau, F. Nolè, S. Lo Vullo, F. Tettamanzi, L. Hollander, L. Licitra

Research output: Contribution to journalArticlepeer-review

Abstract

Background: B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Patients and methods: Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. Results: A total of 201 patients were randomized 1: 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P=0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR=0.77; 95% CI: 0.53=1.11, P=0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR=0.69; 95% CI: 0.38-1.20, P=0.181). Grade≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P=0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). Conclusion: The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Original languageEnglish
Pages (from-to)2820-2826
Number of pages7
JournalAnnals of Oncology
Volume28
Issue number11
DOIs
Publication statusPublished - 2017

Keywords

  • Cetuximab
  • Cisplatin
  • EXTREME
  • Paclitaxel
  • R/M SCCHN
  • cetuximab
  • cisplatin
  • paclitaxel
  • adult
  • aged
  • Article
  • cancer prognosis
  • cancer radiotherapy
  • cancer recurrence
  • controlled study
  • disease severity
  • drug dose reduction
  • drug efficacy
  • drug safety
  • female
  • head and neck squamous cell carcinoma
  • heart disease
  • human
  • incidence
  • intention to treat analysis
  • maintenance therapy
  • major clinical study
  • male
  • median survival time
  • multiple cycle treatment
  • overall survival
  • phase 2 clinical trial
  • priority journal
  • progression free survival
  • randomized controlled trial
  • treatment response
  • treatment withdrawal

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