Patritumab with Cetuximab plus Platinum-Containing Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: An Open-Label, Phase Ib Study.
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Date
2019-01-15Author
Dillon, MT
Grove, L
Newbold, KL
Shaw, H
Brown, NF
Mendell, J
Chen, S
Beckman, RA
Jennings, A
Ricamara, M
Greenberg, J
Forster, M
Harrington, KJ
Type
Journal Article
Metadata
Show full item recordAbstract
PURPOSE: Patritumab plus cetuximab with platinum as first-line therapy for patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) was evaluated for safety and to determine the recommended phase II combination dose. PATIENTS AND METHODS: Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18 mg/kg loading dose; 9 mg/kg maintenance dose every 3 weeks) + cetuximab (400 mg/m2 loading dose; 250 mg/m2 maintenance dose weekly) + cisplatin (100 mg/m2 every 3 weeks) or carboplatin (AUC of 5) for six cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities [DLT; grade ≥3 (21-day observation period)] and treatment-emergent adverse events (TEAE). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS: Fifteen patients completed a median (range) of 8.7 (2.0-20.7) patritumab cycles. No DLTs were reported. Serious adverse events were reported in 9 patients (patritumab-related n = 4). TEAEs (N = 15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics (N = 15) showed mean (SD) AUC0-21d of 2,619 (560) μg/day/mL and maximum concentration of 499.9 (90.4) μg/mL. All patients were HAHA-negative at study end (single, transient low titer in 1 patient). Tumor response rate (complete plus partial response; N = 15) was 47%. Median (95% confidence interval) PFS and OS (N = 15) were 7.9 (3.7-9.7) and 13.5 (6.6-17.5) months, respectively. CONCLUSIONS: Patritumab (18 mg/kg loading dose, 9 mg/kg maintenance dose) plus cetuximab/platinum was tolerable, active in SCCHN, and selected as the phase II dose regimen.
Collections
Subject
Humans
Neoplasm Metastasis
Recurrence
Platinum
Antineoplastic Combined Chemotherapy Protocols
Neoplasm Staging
Prognosis
Treatment Outcome
Adult
Aged
Middle Aged
Female
Male
Antibodies, Monoclonal, Humanized
Cetuximab
Squamous Cell Carcinoma of Head and Neck
Broadly Neutralizing Antibodies
Research team
Targeted Therapy
Language
eng
Date accepted
2018-10-12
License start date
2019-01
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2019, 25 (2), pp. 487 - 495
Publisher
AMER ASSOC CANCER RESEARCH