NE Oncology Issue – June 2007

Background

Numerous studies have reported clinical activity and tolerability of panitumumab in EGFR-expressing patients with mCRC who had progressed during or after completion of chemotherapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens. A study by Peeters M, et al. presented the pooled safety data of panitumumab monotherapy from ten phase I to III clinical trials.1

Study design

  • Patients with mCRC and ECOG PS 0-2 were included in the study. One patient was ECOG PS 3.
  • Pooled safety data from ten clinical studies (n = 966) of panitumumab monotherapy in patients with mCRC were examined.
  • Panitumumab was generally administered by infusion over 30 to 60 minutes per protocol. Premedication was not required. The dosing schedule is shown in Table 1.
  • Primary endpoints were clinical safety events such as incidence of adverse events, including skin-related toxicity and infusion reactions; deaths; drug exposure and incidence of dose changes; and immunogenicity of panitumumab.
  • Secondary endpoints were changes in metabolic and laboratory assessments after panitumumab infusions.

Key findings

  • Safety results are summarized in Tables 2, 3, and 4.
  • There were 149 (15%) patients who died during the study (including deaths within 30 days of last dose of panitumumab). Two deaths were considered by investigators to be treatment related:
    • Pulmonary edema was seen in a patient with a history of hypercoagulation, deep vein thrombosis, peripheral vascular disease, and diabetes mellitus.
    • Myocardial infarction and cerebrovascular accident were observed in a patient with history of anemia, diabetes mellitus, deep vein thrombosis, hyperlipidemia, hypertension, and supraventricular tachycardia.
  • Antibodies to panitumumab
    • Of those patients who were predose negative and had persistent postdose positive results:
    • ELISA found 2/778 patients (0.3%) tested positive for anti-panitumumab antibodies.
    • Biacore found 2/638 patients (0.4%) tested positive for anti-panitumumab antibodies.
    • Bioassay determined 6/638 patients (1%) had neutralizing antibodies to panitumumab.

Key conclusions

  • Panitumumab was generally well tolerated with a consistent toxicity profile across studies.
  • Common toxicities included fatigue, gastrointestinal side effects, and skin-related (the majority were grade 1 or 2).
  • Figure 1 shows the incidence of skin-related adverse events.
  • Grade 3 or 4 infusion reactions were rare (0.4% of patients); no premedication was required.
  • Treatment-related adverse events of grade 3 or 4 were reported in 20% of patients.
  • Four percent of patients permanently discontinued panitumumab or withdrew from the study due to treatment-related adverse events.
  • Anti-panitumumab antibody formation postdose was detected in <1% of patients by ELISA and Biacore.

Reference: 1. Peeters M, Van Cutsem E, Berlin J. Safety of panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR), in patients (pts) with metastatic colorectal cancer (mCRC) across clinical trials. Program and abstracts of the 43rd American Society of Clinical Oncology Annual Meeting; June 1–5, 2007; Chicago, Illinois; Abstract 4138.

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Contributors

dr-hirsh
Vera Hirsh, MD, FRCPC
Chief of the Hematology-Oncology Service, Santa Cabrini Hospital
Associate Professor, Medicine and Oncology, McGill University
Associate Physician, Oncology Service, at the Royal Victoria, Montreal General, and Montreal Chest Hospitals
With a current practice in both hematology and oncology, Dr. Vera Hirsh is an associate professor of medicine and oncology at McGill University. Her research at the Quebec Pulmonary Unit focuses on the treatment of lung cancer, and she continues to chair ongoing international chemotherapy trials. Dr. Hirsh chaired the Quebec Lung Cancer Committee to establish guidelines for the treatment of lung cancer. In addition, she has published abstracts, articles, and book chapters. Dr. Hirsh is a member of advisory boards for many pharmaceutical companies and the Medical Oncology Standing Committee of RTOG.

dr-cripps
Christine Cripps, MD, FRCPC
Medical Oncologist, Director,
Continuing Medical Education,
Ottawa Hospital Regional Cancer Centre
Dr. Christine Cripps is a medical oncologist and director of the Continuing Medical Education Department at the Ottawa Hospital Regional Cancer Centre. She also holds a position of Associate Professor, Medicine at the University of Ottawa. A keen teacher, Dr. Cripps’ main areas of interest include gastrointestinal cancer and head and neck cancer. She also enjoys cycling, skiing, and sailing when time permits.

dr-chia
Stephen K. L. Chia, MD, FRCPC
Assistant Professor of Medicine Department of Medicine
University of British Columbia
British Columbia Cancer Agency
Dr. Chia is a staff oncologist with the British Columbia Cancer Agency (BCCA), Vancouver, Canada. He also serves as physician coordinator for both the breast cancer and head and neck cancer clinical trials at the BCCA – Vancouver Cancer Centre. He is an active researcher in phase I-III trials in breast cancer, head and neck cancer and investigational new drugs. He is currently carrying out studies in breast cancer with grant funded research from the National Cancer Institute of Canada, Canadian Breast Cancer Alliance and Canadian Breast Cancer Foundation – British Columbia/Yukon Chapter. Dr. Chia is an active member of the British Columbia Breast Tumor Group, Breast Cancer Systemic Policy Group and Head and Neck Tumor Group.

dr-chang
José Chang, MD, FRCPC
Head of Medical Oncology, RS
McLaughlin Durham Regional Cancer Centre, Oshawa
Dr. José Chang is the principal investigator and site representative for the National Cancer Institute of Canada Clinical Trials Group, and is an examiner for the Medical Council of Canada. His research interests lie in the areas of breast cancer, melanoma, lymphoma, and quality of life during chemotherapy. Dr Chang has presented at major oncology meetings of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposia, and European Breast Cancer Conference. A member of the editorial board of the journal Current Oncology, Dr. Chang has published in journals such as the Journal of Clinical Oncology, European Journal of Cancer, and Canadian Medical Association Journal.