From: Fran Visco, President
National Breast Cancer Coalition
You have probably heard about the National Cancer Institute press release today of the results of a breast cancer trial.
Unfortunately, the National Cancer Institute has again stopped a breast cancer trial early, on the basis of interim results. A multicenter randomized placebo-controlled clinical trial of Letrozole indicated that after five years of tamoxifen therapy, and an average of 2.4 years of follow-up, the risk of breast cancer recurrence was lower in the Letrozole group.
Recurrence included local, contralateral and metastatic events. We certainly hope that long term this use of Letrozole is of benefit to women with breast cancer. However, this trial should not have been stopped.
We don't know the long term side effects, which could outweigh the benefit of fewer recurrences. More importantly, recurrence is an interim outcome measure, and is not the correct end point for this trial.
The study should not have been stopped unless a marked mortality benefit was shown for one of the two interventions or if it had been futile to continue, because no difference between the two groups was likely to emerge.
You should recall the lumpectomy vs. mastectomy trials. All data combined indicate that having a mastectomy results in fewer recurrences than lumpectomy.
Yet, over the long term, women die at the same rate regardless of which surgery they receive. If we had relied on recurrence data for assessing the relative values of the two surgeries, women would still be getting mastectomy and not lumpectomy. It is extremely important that we understand how to analyze clinical trials in order to evaluate information we receive from the research and provider communities.
NBCC is in the process of releasing a fact sheet on study end points that will help advocates going forward.
For your information, the letrozole trial was a double blind, placebo controlled study designed to determine whether giving patients the aromatase inhibitor, letrozole, for 5 years after they had already completed approximately 5 years of Tamoxifen therapy would improve recurrence or survival.
It looked at 5187 women who were postmenopausal, had early stage breast cancer, and had completed Tamoxifen therapy. Half got letrozole and half got placebo.
When the interim analysis was performed, the DSMB found that 132 women in the placebo group had experienced a disease recurrence, while only 75 of the women in the letrozole group had experienced recurrence.
A total of 42 women in the placebo group and 31 women in the letrozole group had died (p=0.25 for overall survival). The median follow up was 2.4 years. The Kaplan Meier estimates for four -year disease free survival were 93% in the Letrozole group and 87% in the placebo group (P<0.001).
Based upon the reductions in recurrence and the Kaplan Meier survival estimates, the DSMB decided to halt the trial, unblind the study, and notify the women.
The press releases from NCI quote the investigators as saying that based upon these findings, women should discuss 3 years of Letrozole with their doctor after completing Tamoxifen therapy.
The biggest issues here are that the follow up is extremely short and the end point of recurrence is not meaningful . Letrozole is an aromatase inhibitor like Anastrazole, and we don't have the data yet to know what the long term effects of this treatment might be, particularly in terms of osteoporosis or cognition.
We will need to continue to follow these women to determine the full side effects and benefits of this treatment. In the meantime, women need to know that we don't fully understand the long term effects of this drug yet.
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