I thought this excerpt from the "Interactive Dialogue Session: Clinical Considerations and Debates in Adjuvant Therapy," a panel discussion by Adam M. Brufsky, MD, PhD, Michael Gnant, MD, Matthew R. Smith, MD, PhD, was worth posting:
Adam M. Brufsky, MD, PhD:
In North America, clinicians tend to treat early breast cancer patients with endocrine therapy for 5 years. However, in the ABCSG-12 trial, the patients with hormone-responsive, early-stage breast cancer were treated for only 3 years.Why?
Michael Gnant, MD:
This is a very good question. Because ABCSG is an academic trialist group, the studies are usually built one after the other. The predecessor trial of ABCSG-12 was ABCSG-5, which showed that 3 years of goserelin plus 5 years of tamoxifen—the standard durations for these therapies—was significantly more effective for adjuvant treatment of premenopausal patients with stage I/II breast cancer compared with 6 cycles of
cyclophosphamide, methotrexate, and fluorouracil.This earlier trial established that endocrine therapy benefits patients with early-stage breast cancer. In ABCSG-12, women were randomly assigned to receive goserelin 3.6 mg subcutaneously every 28 days plus tamoxifen 20 mg/day orally or anastrozole 1 mg/day orally with or without zoledronic acid 4 mg intravenously every 6 months for 3 years. The AI (ie, anastrozole) could not be used alone without ovarian function suppression. As such, we would have had to increase the duration of ovarian function suppression to 5 years, which for a variety of reasons we did not want to do, or switch all AI patients back to tamoxifen during Years 4 and 5, which would have made the statistical analysis very complicated. My colleagues and I decided that we would take the risk and offer patients a limited treatment duration of 3 years. Although these treatments are better tolerated than chemotherapy, they are not without adverse events. Limiting the duration of endocrine therapy holds value, particularly for younger women. I believe that the overall outcome of the trial makes it very difficult to claim that 5 years of AI treatment would have been more effective than 3 years. The data revealed 3-year disease-free survival rates of 92.8% in the tamoxifen group vs 92.0% in the anastrozole group.
Adam M. Brufsky, MD, PhD:
I would like to focus on this issue. Clearly, this large trial provides data assessing 3 years of endocrine therapy. Based on these findings, can one make the argument that it is reasonable to consider 3 as opposed to 5 years of endocrine therapy?
Michael Gnant, MD:
To firmly draw a conclusion, this issue needs to be tested prospectively. However, the data do suggest that 3 years of therapy may be sufficient. All other endocrine interventions except for tamoxifen were never really proven to produce better outcomes with a 5-year duration. Studies of tamoxifen defined the standard duration of 5 years based on better efficacy compared with 2 or 3 years of treatment. This was then extrapolated to all other endocrine interventions. However, there is evidence to suggest that shorter durations of AIs may be sufficient.
(emphasis added)
Food for thought.
Hopeful