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 |
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| Institution: | 1. Head and Neck Medical Oncology, Fondazione IRCCS – Istituto Nazionale dei Tumori, Milan University of Milan, Milan;2. Clinical Epidemiology and Trial Organization, Fondazione IRCCS – Istituto Nazionale dei Tumori, Milan;3. Medical Oncology, Ospedale San Paolo, Milan;4. Medical Oncology, IRCCS San Martino, IST National Cancer Institute, Genova and University of Genova, Genova;5. Medical Oncology, Azienda Ospedaliera Arcispedale Santa Maria Nuova – IRCCS, Reggio Emilia;6. Medical Oncology, St. Croce & Carle University Teaching Hospital, and ARCO Foundation, Cuneo;7. Medical Oncology, Istituto Nazionale Tumori – IRCCS – Fondazione Pascale, Naples;8. 2nd Medical Oncology Division, Città della Salute e della Scienza Hospital of Turin, Turin;9. Medical Oncology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo;10. Medical Oncology, Centro di Riferimento Oncologico, Aviano;11. Medical Oncology, A.O. Universitaria Maggiore della Carità, Novara;12. Medical Oncology, Ospedale Santa Chiara, Trento;13. Medical Oncology, AOU Policlinico “Paolo Giaccone,” Palermo;14. Medical Oncology, Ospedale San Vincenzo, Taormina;15. Medical Oncology, Istituto Europeo di Oncologia, Milan;16. Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy |
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| Abstract: | BackgroundB490 (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 methodsEligible 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.ResultsA 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%).ConclusionThe 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.Clinical trial numberEudraCT# 2011-002564-24. |
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