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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

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Abstract

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.

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Acknowledgments

The independent data monitoring committee consisted of Dr. Jens Benn-Sørensen (Department of Oncology, The Finsen Centre, Rigshospitalet, National University Hospital, Denmark), Dr. med. Torkil Menné (Department of Dermatology, KAS-Gentofte, Denmark), and Dr Barbara Ann Burtness (Fox Chase Cancer Center, USA). We thank the patients and the following investigators in the Hx-EGFR-205 Study Group for their participation in the study: Austria; Dr. Gabriela Veran Kornek (Vienna); Czech Republik; Dr. Petra Holečková (Prague), Dr. Hana Honova (Prague), Dr. Lubomir Slavicek (Jihlava); Germany; Dr. Gerhard Dyckhoff (Heidelberg), Dr. Markus Hambek (Frankfurt), Dr. Jens Büntzel (Nordhausen); Israel; Dr. Rami Ben-Yosef (Tel-Aviv), Dr. Raphael Pfeffer (Ramat-Gan), Dr. Tal Grenader (Jerusalem), Dr. Konstantin Lavrenkov (Beer Shiva); Italy; Dr. Franco Nolé (Milan); Portugal; Dr. Isabel Goulão Sargento (Lisboa), Dr. Isabel Pazos Portela (Coimbra); Slovak Republik; Dr. Ludovit Jurga (Trnava), Dr. Tomas Minarik (Bratislava); Chile; Dr. Eduardo Patricio Yañez Ruiz (Temuco), Dr. Pablo Gonzalez Mella (Vina del Mar), Dr. Jose Antonio Solis Campos (Valparaiso); Colombia; Dr. Manuel Enrique Gonzalez (Monteria); Peru; Dr. Julio Santiago Guevara Guevara (Lima), Dr. Lucila Regina Morla Chiong Kongfook (Lima), Dr. Diana Sofia Aleman Polanco (Arequipa); USA; Eben Rosenthal (Birmingham, AL), Tawee Tanvetyanon (Tampla, FL), Dr. Tanguy Seiwert (Chicago, IL), Sreenivasa Nattam (Fort Wayne, IN), Neil Senzer (Dallas, TX), Neil Gross (Portland, OR), Mary Jo Fidler (Chicago, IL), Theodore Walters (Boise, ID), Chung-Tsen Hsueh (Loma Linda, CA), Lucio Gordan (Gainsville, FL). This study was designed and funded by Genmab, who also had oversight over the study, safety reporting, data collection and assembly as well as data interpretation.

Conflict of interest

VS has no conflicts of interest. EC has consultant role for Boehringer Ingelheim, Novartis, Genmab, Bristol Myers Squibb, AstraZeneca and Exelixis. LL has advisory/consultant role for BMS, Glaxo, Lilly, Merck-Serono, Amgen, Boehringer Ingelheim and Pfizer. JD has advisory/consultant role for Amgen and Merck-Serono and has received honoraria from Merck-Serono. SL is senior medical director of Genmab and holds stock options. TG has advisory/consultant role for Amgen, Boehringer Ingelheim, Genmab, Merck-Serono and Novartis and has received honoraria from Amgen, Boehringer Ingelheim and Merck-Serono.

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Authors and Affiliations

  1. Section of Hematology and Oncology, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL, 60637, USA

    Vassiliki Saloura

  2. Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, 3855 Health Sciences Drive, #0658, La Jolla, CA, 92093, USA

    Ezra E. W. Cohen

  3. Head and Neck Medical Oncology Unit, Fondazione IRCCS Instituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy

    Lisa Licitra

  4. The Oncology Institute, Rambam Medical Center, 8 Aalia Street Bat Galim, 31096, Haifa, Israel

    Salem Billan

  5. Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E., Rua Dr. Antonio Bernardino de Almeida, 4200-072, Porto, Portugal

    Jose Dinis

  6. Genmab, Bredgade 34, 1260, Copenhagen, Denmark

    Steen Lisby

  7. Department of Medical Oncology, West German Cancer Center, University Hospital Essen of University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany

    Thomas C. Gauler

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  1. Vassiliki Saloura
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Correspondence to Ezra E. W. Cohen.

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Saloura, V., Cohen, E.E.W., Licitra, L. et al. 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. Cancer Chemother Pharmacol 73, 1227–1239 (2014). https://doi.org/10.1007/s00280-014-2459-z

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  • DOI: https://doi.org/10.1007/s00280-014-2459-z

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