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, C Moro, E Vaccher, A Sponghini, A Caldara, G Rinaldi, F Ferrau, F Nolè, S Lo Vullo, F Tettamanzi, L Hollander, L Licitra

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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.

Original languageEnglish
JournalAnnals of Oncology
DOIs
Publication statusPublished - Nov 2017

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Paclitaxel
Cisplatin
Disease-Free Survival
Arm
Pharmaceutical Preparations
Hypopharynx
Oropharynx
Paranasal Sinuses
Poisons
Drug Combinations
Therapeutics
Larynx
Mouth
Disease Progression
Sepsis
Maintenance
Clinical Trials
Safety
Survival
Cetuximab

Keywords

  • Journal Article

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

In: Annals of Oncology, 11.2017.

Research output: Contribution to journalArticle

Bossi, P, Miceli, R, Locati, LD, Ferrari, D, Vecchio, S, Moretti, G, Denaro, N, Caponigro, F, Moro, C, Vaccher, E, Sponghini, A, Caldara, A, Rinaldi, G, Ferrau, F, Nolè, F, Lo Vullo, S, Tettamanzi, F, Hollander, L & Licitra, L 2017, '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', Annals of Oncology. https://doi.org/10.1093/annonc/mdx439
Bossi, P ; Miceli, R ; Locati, L D ; Ferrari, D ; Vecchio, S ; Moretti, G ; Denaro, N ; Caponigro, F ; Moro, C ; Vaccher, E ; Sponghini, A ; Caldara, A ; Rinaldi, G ; Ferrau, F ; Nolè, F ; Lo Vullo, S ; Tettamanzi, F ; Hollander, L ; Licitra, L. / 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. In: Annals of Oncology. 2017.
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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.",
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TY - JOUR

T1 - 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

AU - Bossi, P

AU - Miceli, R

AU - Locati, L D

AU - Ferrari, D

AU - Vecchio, S

AU - Moretti, G

AU - Denaro, N

AU - Caponigro, F

AU - Moro, C

AU - Vaccher, E

AU - Sponghini, A

AU - Caldara, A

AU - Rinaldi, G

AU - Ferrau, F

AU - Nolè, F

AU - Lo Vullo, S

AU - Tettamanzi, F

AU - Hollander, L

AU - Licitra, L

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1093/annonc/mdx439

DO - 10.1093/annonc/mdx439

M3 - Article

C2 - 28950305

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

ER -