NE Oncology Issue – June 2007

Background

Quality of life issues in metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies were examined by Au et al. in the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) and the patient-reported outcome (PRO)–assessed clinical benefit study by Hendlisz et al. The objectives of both studies were to assess the health-related quality of life (HRQoL) as well as survival in patients with advanced colorectal cancer treated with anti-EGFR antibodies: cetuximab for the NCIC CTG CO.17 trial and panitumumab for the Hendlisz et al. study.1,2 A comparison of the two trials is given below.

Study design

Au et al.

  • Metastatic CRC patients with positive tumour membrane staining for EGFR; ECOG PS 0–2 with prior anti-TS therapy; prior irinotecan or oxaliplatin therapy that had either failed for metastatic disease, relapsed within six months or been documented as unsuitable for therapy were enrolled in the study.
  • Patients with prior anti-EGFR therapy were excluded from the study.
  • Patients were randomized (1:1) to cetuximab (400 mg/m2 IV week 1 then 250 mg/m2 IV weekly) with best supportive care (BSC) or BSC alone.
  • The EORTCC OLQ-C30 scale was used to assess:
    • Five functional scales
      • Physical, role, cognitive, emotional, social
    • Global health status
      • Three symptom scale
      • Fatigue, pain, nausea, and vomiting
    • Six single items
      • Dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact
  • HRQoL was assessed at baseline, 4, 8, 16, and 24 weeks regardless of disease progression.
  • The primary endpoint was overall survival.
  • Secondary endpoints were PFS, survival, objective response rate (RECIST criteria), safety, and QoL.
  • The primary HRQoL endpoint was to compare mean change scores of physical function (PF) and global health status (Global) at eight and 16 weeks.
  • Secondary HRQoL endpoints were to compare the proportion of patients with worsened PF and global change scores at eight and 16 weeks; median time to deterioration in PF and global HRQoL; and exploratory HRQoL response analyses of all scales and items (Table 1).

Key findings

Au et al.

  • Significantly prolonged OS, PFS (Figure 2), and improved ORR (p <0.0001) were observed in the cetuximab-treated group versus the BSC group.
  • Safety profile of cetuximab monotherapy was in line with the reported incidence from previous monotherapy studies.

Study design

Hendlisz et al.

  • mCRC patients with positive tumour membrane staining for EGFR; ECOG PS 0–2 with prior fluoropyrimidine, irinotecan, and oxaliplatin therapy; and disease progression during or within 6 months following most recent chemotherapy regimen were enrolled in the study.
  • Patients with prior anti-EGFR therapy were excluded from the study.
  • Patients were randomized (1:1) to panitumumab (6.0 mg/kg Q2W) with BSC or BSC alone.
  • The NCCN/FACT Symptom Index (FCSI) assessed the most clinical relevant (clinician-rated) symptoms for assessing symptomatic response to treatment for CRC.
  • The EuroQoL EQ-5D Health Index was used to provide a preference-weighted assessment of overall QoL across five dimensions such as mobility, self-care, usual activity, pain or discomfort, and anxiety or depression.
  • The EuroQoL EQ-5D Visual Analog Scale (VAS) assessed overall health status.
  • The EORTC QLQ-C30 global health status and QoL scale were used to assess two items of the EORTC QLQ-C30, measuring overall health status and overall QoL.
  • HRQoL was assessed at:
    • Baseline, every two weeks during treatment, and 30-day safety follow-up visit after the last protocol-directed therapy for the FCSI scale
    • Baseline, monthly during treatment, and 30-day safety follow-up visit after the last protocol-directed therapy for the EQ-5D health and visual analog index, and EORTC QLQ-C30 global health status/QoL scales.
  • The primary endpoint was PFS (Figure 1).
  • Secondary endpoints were OS, best objective response, safety, disease-related symptoms, and HRQoL.
  • The primary HRQoL endpoints of the primary PRO analysis were to assess difference (95% CI) in FCSI and EQ-5D scores at 4, 8, 12, and 16 months for panitumumab minus BSC patients, and association of PFS with CRC symptoms and HRQoL (Table 1).

Key findings

Hendlisz et al.

  • Significant decrease in target lesions was observed in 42% panitumumab patients versus BSC patients (3%).
  • Tumour burden reduction was associated with better QoL and disease-related symptoms.
  • Among patients with stable disease (at week 8 assessment)
    • A target lesion decrease was found in 72% of panitumumab patients, with an overall median decrease of 14%.
    • A target lesion decrease was found in 14% of BSC patients, with an overall increase of 8% in target lesions.

Key conclusions

Au et al.

  • Improved physical function and global health at 8 and 16 weeks in cetuximab patients versus BSC patients (Table 2).
  • Better HRQoL observed with cetuximab than BSC alone.
  • Significantly less HRQoL deterioration and a longer time before this deterioration occurred in patients on cetuximab.
  • The NCIC CTG CO-17 trial demonstrates that cetuximab offers survival and HRQoL benefits for patients with advanced colorectal cancer.

Hendlisz et al.

  • There was a trend in panitumumab patients towards better HRQoL (Table 2) and CRC symptomatology.
  • Lack of disease progression at week 8 was associated with reduced CRC diseases symptoms and higher HRQoL in panitumumab patients.
  • HRQoL was not impacted by the higher rate of skin-related events reported by panitumumab patients compared to BSC patients.

References: 1. Au H, Karapetis C, Jonker D, et al. Quality of life in patients with advanced colorectal cancer treated with cetuximab: results of the NCIC CTG and AGITG CO.17 trial. Program and abstracts of the 43rd American Society of Clinical Oncology Annual Meeting; June 1–5, 2007; Chicago, Illinois; Abstracts 4002. 2. Hendlisz A, Van Cutsem E, Peeters M, et al. Patient-reported outcome (PRO)-assessed clinical benefit with panitumumab (Pmab) in metastatic colorectal cancer (mCRC) patients (pts). Program and abstracts of the 43rd American Society of Clinical Oncology Annual Meeting; June 1–5, 2007; Chicago, Illinois; Abstract 6560.

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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.