NE Oncology Issue – June 2007


Skin toxicities are a common side effect with EGFR inhibitor treatment. Results from the pivotal phase III trial for cetuximab indicate that there may be a physiologic correlation between the onset of skin toxicity and anti-EGFR response.1 Berlin, et al. conducted an exploratory analysis of pooled data from five clinical studies of panitumumab monotherapy to assess the association between severity throughout treatment of skin-related toxicity and panitumumab efficacy, as well as to evaluate the predictive value of skin toxicity severity in the first four weeks for response to panitumumab.2

Study design

  • Data from five clinical trials (n = 727) were pooled (three phase II and two phase III studies).2 Patients with mCRC had documented progression of disease on or after 5-FU, oxaliplatin, and/or irinotecan. Patients received panitumumab 6 mg/kg every two weeks (Q2W) or 2.5 mg/kg weekly until disease progression or intolerability. Tumours were assessed using modified WHO or RECIST criteria (blinded central review in four or five studies).
  • Enrolled patients with a pathologic diagnosis of colorectal cancer who had an ECOG PS 0–2 in four studies, and PS 0–1 in one study.
  • In four out of the five trials, radiographic documentation of disease progression was carried out during or within 6 months after the most recent chemotherapy of fluoropyrimidine with:
    • Irinotecan ≥65 mg/m2/week for eight weeks
    • Oxaliplatin ≥30 mg/m2/week for six weeks
  • Endpoints were objective response rate, PFS, duration of response, time to response, and safety events including skin toxicities, infusion reactions, and anti-panitumumab antibody formation.

Key findings

  • Eighteen percent of patients developed grade 2 to 4 skin toxicity after week four. Thirty-two patients were excluded from this analysis as they did not develop skin toxicity.
  • Severity of skin toxicity in the first four weeks was found to be a predictive factor for PFS (HR = 0.85 [95% CI: 0.73, 0.99]; p = 0.0332) and OS (HR = 0.79 [95% CI: 0.67, 0.93]; p = 0.0052).
  • Severity of skin toxicity throughout treatment was found to be significantly associated with progression-free survival (HR = 0.66 [95% CI: 0.56, 0.78]; p < 0.0001) and overall survival (HR = 0.62 [95% CI: 0.52, 0.74]; p < 0.0001).

Key conclusions

  • Severity of toxicity in the first four weeks was found to be a predictive factor for PFS and OS, but not for objective response rate.
  • Severity of toxicity throughout treatment was associated with a greater chance for objective response and better PFS and OS.
  • Among patients with grade 2 to 4 skin toxicity, 18% of patients did not experience grade 2 or higher toxicity until after week four.
  • Among all patients with grade 2 to 4 skin toxicity, the response rate was 11.3%.
  • Overall, patients with a higher skin toxicity appear to have a better prognosis.

References: 1. McKarney L. Advances in the treatment of metastatic colorectal cancer. New Evidence in Oncology 2006;5:14–19. 2. Berlin J, Van Cutsem E, Peeters E, et al. Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): a pooled analysis of five clinical trials. Program and abstracts of the 43rd American Society of Clinical Oncology Annual Meeting; June 1–5, 2007; Chicago, Illinois; Abstract 4134.

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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.

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.

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.

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.