Wednesday, May 01, 2019 Updated results of the CCTG MAC.7 | SWOG 0226 study have recently been published in the New England Journal of Medicine. Long-term results of a phase III trial showed that women with metastatic hormone-sensitive breast cancer lived nearly 8 months longer with the addition of fulvestrant (Faslodex) to first-line anastrozole (Arimidex). The objective of the trial was to compare time to tumour progression in post-menopausal women with metastatic breast cancer treated with anastrozole versus anastrozole and fluvestrant. It is know that estrogen can stimulate the growth of breast cancer cells. It was thought that hormone therapy with drugs such as anastrozole and fulvestrant may help fight breast cancer by blocking estrogen. “The MAC.7 |SWOG 0226 clinical trial employed a rational approach using combined blockade with an estrogen receptor down-regulator that also blocks cross-talk as a mechanism of anti-estrogen resistance in addition to an aromatase inhibitor, anastrozole,” says Dr. Ted Vandenberg, Oncologist and researcher at the London Health Sciences Centre and the Canadian study chair. “The fact that the overall survival benefit persists after seven years of follow up and despite crossover of 45% of patients progressing on anastrozole to fulvestrant adds to the strength of the conclusions.” The MAC.7 study showed greater benefit occurred in women who were never exposed to adjuvant tamoxifen therapy. The 7.8 month difference in survival (42.0 vs 49.8 months) was both statistically and also clinically meaningful, however more research needs to be done to understand these outcomes. Other similar studies have not shown these results including the FACT and SoFEA trials. There are some hints why this may be the case. “I think the next question would be what would have happened if fulvestrant was used at higher dose as in the FALCON trial?”, questions Dr. Vandenberg. “We need a better understanding of mechanisms of resistance and markers to identify groups that will benefit. Since combination therapy seemed to work in this trial, it may be worth revisiting combination therapy once more.” CCTG contributed 44 of the 707 patients randomized to this study. https://www.nejm.org/doi/full/10.1056/NEJMoa1811714
