Tamoxifen vs Letrozole
As you may know, there have been many studies, over the past years, examining the relative value of tamoxifen vs the AIs for post menopausal women with ER positive breast cancer. A number of strategies have been explored (one or the other for five years, Tam for 5 years and then an AI, Tam for 2-3 years, and then an AI, etc). This is the report of a new study which indicates that Letrozle is more helpful in this setting than Tamoxifen. Word of caution: More helpful by a bit. This does not mean that Tamoxifen is not a very helpful drug. This becomes especially important financially for some women whose insurance does not fully cover the cost of these medications. This does not mean that it is worth re-mortgaging the house to pay the difference between the two drug costs. There are also women who have other medical issues that make one or the other drug the better choice. As always, this is a "talk with your doctor" situation.
BIG Results for Letrozole vs Tamoxifen in Early Breast Cancer
Lidia Schapira, MD
Assessment of Letrozole and Tamoxifen Alone and in Sequence for Postmenopausal Women With Steroid Hormone Receptor-positive Breast Cancer: the BIG 1-98 Randomized Clinical Trial at 8.1 Years Median Follow-up
Regan MM, Neven P, Giobbie-Hurder A, et al Lancet Oncol. 2011;12:1101-1108
The study by Regan and colleagues presents an update on efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8.1 years median follow-up. BIG 1-98 is a randomized, phase 3, double-blind trial of postmenopausal women with hormone-receptor positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of the drugs followed by 3 years of the other. After a significant disease-free survival benefit was reported in 2005 for letrozole compared with tamoxifen, a protocol amendment allowed the crossover to letrozole for those patients who were still receiving tamoxifen alone. These investigators used new statistical methods including inverse probability of censoring weighting (IPCW) to account for this selective crossover. The analysis includes patients who received monotherapy and sequential therapy. Treatment has ended for all patients and follow-up is ongoing.
After a median follow-up of 8.7 years, letrozole monotherapy was found to be significantly better than tamoxifen with respect to overall survival, whether reviewed by IPCW or intention to treat analysis. At a median follow up of 8 years from randomization, the letrozole alone group did just as well as those who had been randomized to sequential therapy.
The findings assessed by longer follow-up and improved statistical instruments showed no benefit to sequential endocrine therapy over letrozole alone for postmenopausal women with early-stage breast cancer. Overall survival was identical for patients receiving letrozole alone or as part of sequential therapy. The authors conclude that sequential therapies may be useful strategies when considering individual patient risks of recurrence and treatment tolerability, although they do not provide any advantage in terms of cancer specific outcomes.
This is an important contribution to our knowledge base and will affect clinical practice. We will likely see more of these sophisticated statistical analyses and thanks to the long-term follow-up included in adjuvant endocrine trials will learn enough to provide solid guidance to patients. The bottom line in this paper is that letrozole alone for 5 years is as good as a sequential treatment using both drugs for a total of 5 years. Oncologists will have to bear this in mind as they counsel women who have difficulties tolerating aromatase inhibitors, such as the unpleasant musculoskeletal side effects associated with their use.
Ongoing studies investigating the possible benefits of prolonged administration of aromatase inhibitors will affect our recommendations going forward. For now, it is fair to say that the evidence favors the use of aromatase inhibition as adjuvant therapy for postmenopausal women, either alone or after tamoxifen. When giving advice, oncologists need to consider a patient's comorbid conditions -- specifically bone health, cardiovascular risk, and the burden of menopausal symptoms -- as well as her risk of cancer recurrence and mortality. Sequential therapy may still be an attractive option for many of our patients.
Medscape Hematology-Oncology © 2011 WebMD, LLC
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