NE Oncology Issue – June 2007

Background

The taxane paclitaxel is highly effective against breast cancer, both as monotherapy and in combination with other agents. Solvents such as cremophor and ethanol are conventionally used as vehicle formulations for solubilizing paclitaxel. These solvents are associated with side effects that can limit drug efficacy, including prolonged and sometimes irreversible neuropathy, myelosuppression, hypersensitivity reactions, and excessive fluid retention.1 Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a solvent-free formulation of paclitaxel, has been demonstrated to have improved efficacy and less toxicity compared with solvent-based paclitaxel in the treatment of metastatic breast cancer.2 The study by Guan et al. was undertaken to compare the response rate and evaluate the safety of nab-paclitaxel versus solvent-based paclitaxel in Chinese patients with metastatic breast cancer.3

Study design

  • The study was a large randomized, multicentre phase III trial.
  • A total of 212 patients with a median age of 50 years and an Eastern Cooperative Oncology Group (ECOG) performance score of 0 were randomly assigned to either nab-paclitaxel or solvent-based paclitaxel.
  • Eligible patients had histologically or cytologically confirmed breast cancer with evidence of recurrence or metastasis and had either no prior chemotherapy or had progressed on prior chemotherapy for metastatic breast cancer.
  • There were no important differences between the two groups with regards to baseline characteristics.
  • Each patient received up to six cycles of treatment.
  • Patients who completed six cycles of therapy and did not have progressive disease could continue their arm of treatment at the investigator’s discretion until progression or unacceptable toxicities.
  • Patients who had received at least one dose of the study drug were evaluated for overall response rate (ORR), time to progression (TTP), progression-free survival (PFS), overall survival (OS), and toxicity.

asco07-2-study-lrg

Key findings

  • A highly significant overall response rate of 54% versus 29% (p <0.001) was observed in patients on the nab-paclitaxel arm of the study as compared with patients on the solvent-based paclitaxel arm (Table 1).
  • Overall response rates were higher in patients with no prior adjuvant or metastatic anthracycline therapy and in patients undergoing first-line nab-paclitaxel therapy.
  • There were similar incidences of alopecia and peripheral neuropathy between treatment arms. These were the most common toxicities observed in both arms.
  • The incidence of neutropenia (all grades) was greater with nab-paclitaxel than with solvent-based paclitaxel (93% versus 77% respectively, p = 0.029).
  • The incidence of grade 3 and 4 neutropenia was similar between both groups (45% versus 37% respectively, p = 0.258).
  • Skin reactions were significantly higher in the nab-paclitaxel arm. All reactions were grade 1 or 2, and most resolved without treatment. Dosing of nab-paclitaxel was not affected by development of skin reactions.

Key conclusions

  • nab-paclitaxel (260 mg/m2) every three weeks demonstrated a significantly higher response rate and median time to progression than solvent-based paclitaxel (175 mg/m2). This result is consistent with the results obtained in Caucasian patients.2
  • The overall response rate was also greater in patients with no prior anthracycline therapy and in patients undergoing first-line nab-paclitaxel treatment.
  • Overall, the incidence of neutropenia was greater with nab-paclitaxel, but incidence of grade 3 or 4 neutropenia was similar in both treatment arms.
  • Occurrence of sensory neuropathy was similar in both treatment arms, despite a 49% higher paclitaxel dose administration in the nab-paclitaxel arm.

References: 1. Winer EP, Berry DA, Woolf S, et al. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol 2004;22:2061–2068. 2. Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 2005;23:7794–7803. 3. Guan Z-Z, Feng F, Li QL, et al. Randomized study comparing nab-paclitaxel with solvent-based paclitaxel in Chinese patients (pts) with metastatic breast cancer (MBC). Program and abstracts of the 43rd American Society of Clinical Oncology Annual Meeting; June 1–5, 2007; Chicago, Illinois; Abstract 1038.

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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.