The Emperor Has No Clothes
The title above is the tantalizing one from an editorial by Doctors Bostjan and Tannock from Princess Margaret Hospital in Toronto that is in a recent issue of the Journal of Clinical Oncology. They write about the disappointing realities of the upfront use of AIs vs tamoxifen for women with early stage hormone positive breast cancers. The bottom line is that DFS (disease-free survivial, that is the length of time before a cancer recurrence) is slightly longer in the cohort of women who received AIs, but overall survival (how long they lived) is the same. Since there are some serious possible side-effects of the AIs, this is a very important finding. As always, one article or study does not and should not change standard practice/care, but this likely will make a difference in the way that oncologists think about hormonal treatment choices.
Here is their summary:
In summary, recent evidence from clinical trials does not support the routine initial use of up-front AIs as adjuvant therapy. Recommendations for their use have beenmadeon the basis of improvement in DFS despite evidence that it is an imperfect surrogate for overall survival, including evidence from serial reports of the ATAC trial (Table 1) and with no evidence of better tolerance or quality of life.
Furthermore, several studies suggesting cost-benefit of up-front anastrozole compared with tamoxifen based their conclusions on the expectation that DFS would translate into improved survival, and at 8 or more years of follow-up, that has not occurred. If AIs do not improve survivalwhencomparedwith tamoxifen, their added cost per life-year gained is infinite, and they are cost-ineffective. Despite the lack of supportive evidence, it is surprising how dramatically patterns of clinical practice have changed to endorse the up-front use of AIs.
Future results from the BIG 1-98 clinical trial may or may not demonstrate benefit in overall survival for the up-front use of letrozole in comparison to tamoxifen alone or to the switching strategy, but on the basis of current data, up-front use of an AI can be recommended only in women who have contraindications to the use of tamoxifen.
If you want to read the whole editorial: