P Bossi1, R Miceli2, L D Locati1, D Ferrari3, S Vecchio4, G Moretti5, N Denaro6, F Caponigro7, M Airoldi8, C Moro9, E Vaccher10, A Sponghini11, A Caldara12, G Rinaldi13, F Ferrau14, F Nolè15, S Lo Vullo2, F Tettamanzi16, L Hollander16, L Licitra17. 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. 17. Head and Neck Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan University of Milan, Milan. Electronic address: lisa.licitra@istitutotumori.mi.it.
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. CLINICAL TRIAL NUMBER: EudraCT# 2011-002564-24.
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. CLINICAL TRIAL NUMBER: EudraCT# 2011-002564-24.
Authors: Kalyan R Chitturi; Ethan A Burns; Ibrahim N Muhsen; Kartik Anand; Barry H Trachtenberg Journal: Curr Oncol Rep Date: 2022-02-22 Impact factor: 5.075
Authors: Douglas Adkins; Jessica Ley; Omar Atiq; Steven Powell; William C Spanos; Mark Gitau; Caron Rigden; Kevin Palka; Jingxia Liu; Peter Oppelt Journal: Oral Oncol Date: 2021-02-03 Impact factor: 5.337
Authors: Adeline Pêtre; Cécile Dalban; Andy Karabajakian; Eve-Marie Neidhardt; Pierre Eric Roux; Marc Poupart; Sophie Deneuve; Philippe Zrounba; Jérome Fayette Journal: Oncotarget Date: 2018-04-24