An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck

• Published in: Cancer chemotherapy and pharmacology Vol. 73; no. 6; pp. 1227 - 1239
• Main Authors: Saloura, Vassiliki, Cohen, Ezra E. W., Licitra, Lisa, Billan, Salem, Dinis, Jose, Lisby, Steen, Gauler, Thomas C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2014; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cancer Research; Carcinoma, Squamous Cell - drug therapy; Clinical trials; Disease control; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - immunology; Exanthema; Female; Gastrointestinal diseases; General aspects; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - drug therapy; Humans; Hypokalemia; Hypomagnesemia; Male; Medical sciences; Medicine; Medicine & Public Health; Metastases; Middle Aged; Oncology; Original Article; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Patients; Pharmacology. Drug treatments; Pharmacology/Toxicology; Platinum; Pneumonitis; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Safety; Skin; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Subgroups; Survival; Survival Analysis; Titration; Treatment Outcome; Tumors; Epidermal growth factor receptor monoclonal antibody; Platinum-refractory; Squamous cell carcinoma of head and neck; Zalutumumab; Antineoplastic agent; Human; Treatment resistance; Anti-EGFR; Toxicity; Malignant tumor; Monoclonal antibody; Epidermal growth factor receptor; Growth factor receptor; Treatment; Phase II trial; ENT disease; Head and neck cancer; Head and neck squamous cell carcinoma; Cancer
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-014-2459-z

Purpose Treatment options for patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) are limited. The purpose of this study was to assess the efficacy and safety of zalutumumab in platinum-refractory R/M SCCHN. Methods Patients with platinum-refractory R/M SCCHN were enrolled if they had performance status of 0–2, age ≥18 years and adequate organ function. Patients received weekly infusions of zalutumumab individually titrated to a grade 2 skin rash. Primary objective was overall survival (OS), and secondary objectives were efficacy and safety. A subgroup analysis of OS and progression-free survival (PFS) was conducted for various demographic, disease-related and molecular factors. Results Ninety patients were enrolled. Twenty-three percent of patients had performance status (PS) 2 and 74 % had distant metastases. Median OS was 5.3 months (95 % CI [4.1, 7.1]), and median PFS was 2.1 months (95 % CI [2.0, 2.6]). Subgroup analysis by ECOG PS revealed median OS of 6.3 months for PS = 0–1 and 2.5 months for PS = 2. Objective response rate was 5.7 %, and disease control rate was 39.8 %. Grade 3–4 adverse events related to zalutumumab were observed in 19 % of patients and included skin rash (5 %), hypomagnesemia (4 %) and pneumonitis (1 %). The frequency of all-cause grade 3–4 AEs was 62 % and included infections (14 %), gastrointestinal disorders (12 %) and hypokalemia (6 %). Two deaths were deemed related to zalutumumab [ClinicalTrials.gov Identifier: NCT00542308]. Conclusions Zalutumumab showed reasonable efficacy in platinum-refractory R/M SCCHN patients, and dose titration based on skin rash evaluation was feasible.