Description

One of the major advances in the treatment of cancer over the last 10 years is the advent of the humanised monoclonal antibody trastuzumab (Herceptin) which targets the HER-2 gene product. The results of the first three large-scale randomised adjuvant trials have already been presented to professionals and the public alike. The benefits were striking and remarkably consistent across the studies. The BIG HERA trial enrolled 5081 patients worldwide and the results from an interim planned analysis at one year reported a reduction in breast cancer recurrence in the trastuzumab group compared with controls. The investigators measured the following events; any recurrence, second primary events and death. Thirteen percent of patients in the observation arm experienced an event compared with 7.5% patients receiving trastuzumab, a highly significant result equating to a 50% reduction. The absolute reduction in death from all causes was only 0.5%, but the follow up is still very short. The NSABP-B31 and Intergroup NCCTG-9831 trials recruited 3676 patients from the US and Canada. The combined results of these two North American trials reported disease-free patients at three years of 87.1% and 75.4% in the trastuzumab and control groups respectively. The absolute survival rate at three years was 94.3% in the trastuzumab group and 91.7% in the control group, and this result was statistically significant.
In view of these results, adjuvant trastuzumab has become standard therapy for HER-2 positive breast cancer patients receiving chemotherapy in many countries. In the UK, the National Institute for Clinical Excellence (NICE) has expedited an appraisal for trastuzumab, but a decision on funding is still not expected until the middle of 2006. Meanwhile, under pressure from patients and their physicians some local fundholders have provided this treatment for their patients, but many have not. It is to be hoped that lessons can be learned from this experience so that future advances in cancer treatment can be more satisfactorily managed to the benefit of all our patients.
In this issue, your editor gives a short resume of the presentations from the recent 28th Annual San Antonio Breast Cancer Symposium in the USA.
Further data on adjuvant trastuzumab in breast cancer was presented by the BCIRG group and, again, showed virtually identical results to the trials discussed above. However there was also a surprise. A group of investigators from Finland presented an interesting trial comparing adjuvant single agent docetaxel to vinorelbine. However, in HER-2 positive patients there was also a sub-randomisation to just nine weeks of concomitant adjuvant trastuzumab rather than the prolonged durations seen in the previous trials. The results really do provide food for thought, with a clear benefit in preventing disease relapse with a hazard ratio in line with the previous trials. As one of my senior colleagues in the breast cancer world remarked, “In April 2005 we had no information whatsoever on the benefits of adjuvant trastuzumab – but now in November the same year we have clear evidence of benefit from no less than five large scale randomised trials.” With many further questions still to answer, not the least being the optimum duration of therapy, this story will be unfolding for many months to come.