Chaos surrounds high-dose chemotherapy for breast cancer

Abstract

In the past, the American Society of Clinical Oncology has fiercely enforced a policy of no early release of data to be presented at its meetings. But this year, a month before its annual gathering, which starts today in Atlanta, Georgia, ASCO decided to publish abstracts of five randomised trials of highdose chemotherapy for high-risk or advanced breast cancer: only one reports a statistically significant positive result. High-dose chemotherapy for breast cancer effectively ablates the patient's bone marrow and makes a haemopoietic transplant essential. The technique is dangerous (one study reports 7·4% treatment-related mortality), and any benefit is likely to be small. Releasing and discussing early data from the trials, before the conference, is controversial. Most probably, ASCO's hand was forced by a strong story in the Wall Street Journal in March which said that the studies were expected to be negative. That story followed a February meeting convened by the National Cancer Institute in the USA and attended by breast-cancer advocacy groups. ASCO stated, when it released the abstracts in mid-April, that definitive conclusions cannot yet be made. Ric Klausner, NCI director, commented guardedly: “high-dose therapy has not yet been shown to be superior”. The NCI's head of cancer treatment and diagnosis, Robert Wittes, went further: “the information… does not suggest that high-dose chemotherapy with transplants improves survival”. Most of the consumer groups still insist that the high-dose treatment should be available to those women that want it. This is the line taken by, for example, the Susan G Komen Breast Cancer Foundation and the Y-ME Breast Cancer Organization. The National Breast Cancer Coalition takes the opposite view: “the results will not show that this treatment benefits women with breast cancer”. The story of high-dose chemotherapy for breast cancer is turning into a classic example of how not to turn research into practice. Early non-randomised studies gave promising results, and the regimen leaked out into practice before the results of any large randomised phase 3 trials were reported. In Europe, however, oncologists are far more reluctant to give high-dose treatment as routine. The USA has very active breast-cancer consumer groups who aggressively lobby for access to almost any new treatment that offers even the slightest hope. Not surprisingly, many frightened patients decided to gamble on high-dose chemotherapy. As a result, only one in ten US patients who have received high-dose chemotherapy did so within a clinical trial. With so few patients participating in randomised studies, the trials dragged on far longer than expected. Although ASCO and the NCI must be presumed to have the best of intentions, their management of the release of these latest data has only served to muddle the situation further. Both should have known that the public disclosure of controversial medical information needs careful handling, especially in the extremely politicised field of breast cancer. ASCO failed, when commenting on the five studies, to include the findings of three previous randomised studies. Although all were small, two were negative and the positive trial was from the same South African group that will report positively again at this week's conference. Cancer professionals still have one chance to restore some scientific dignity and public confidence. While releasing the data early, ASCO sought to hold its position by saying that the data are yet to be “reviewed and discussed in the scientific community”. That discussion must look critically at whether the interim analyses presented to date were preplanned in the trial protocols. The investigators must also resist calls for subgroup analyses. Because the trials are so diverse, a meaningful meta-analysis is unlikely, and the opportunity for prospective overviews may have been missed. Rigid adherence to what remains of the principles of good practice for clinical trials will limit the damage already done to the reputation of all those involved in breast-cancer treatment and advocacy in the USA. Then the needs of women with breast cancer will be truly served, and seen to be so.