The IBIS-II DCIS study has failed to show any significant differences in the rate of recurrence in postmenopausal women with DCIS who receive anastrozole versus tamoxifen after their surgery.
The study, presented during the 2020 San Antonio Breast Cancer Symposium, randomised 2980 women from 238 centres in 17 countries including Australia to five years of either treatment. Median follow up was 11 .6 years.
The women had a median age of 60.4 years. About 45% had used HRT before entry into the trial and 71% received radiotherapy as part of their initial treatment. The mean tumour size was 17.5 mm and most women had intermediate to high grade disease.
Dr Ivana Sestak, from the Centre for Cancer Prevention at the Queen Mary University London, told the meeting that the study recorded 37 breast cancer recurrences with anastrozole and 45 with tamoxifen after five years of treatment.
“This translates into a non-significant 16% reduction in recurrences with anastrozole compared to tamoxifen,” she said. The absolute risk reduction was 0.4%.
“For the full follow-up period we observed a non-significant 11% reduction in recurrence with anastrozole compared to tamoxifen which translated into an absolute risk reduction of 1.2% with anastrozole.”
Comparing the active treatment period with the post-treatment period, the study found for all recurrences there were similar non-significant reductions with anastrozole in both periods.
“And when we looked at ER positive recurrences we observed a significant 44% reduction with anastrozole compared to tamoxifen however this was only observed during the active follow-up period and no effect was seen thereafter.”
ER- recurrences were similar in the anastrozole and the tamoxifen arms of the study although there was a non-significant increase in recurrences with the aromatase inhibitor after the active follow-up period.
“HER2+ recurrence were significantly reduced by 60% with anastrozole compared to tamoxifen but again, this was only during the active follow-up period in the first five years and not thereafter.”
“And for invasive and DCIS, we observed similar non-significant differences in both follow -up periods.”
“Overall we did not observe a significant effect of anastrozole on reducing rates of recurrence for any breast cancer subtypes,” she said.
Dr Sestak said there was a slight but non-significant increase in other cancers seen in the tamoxifen arm driven by more endometrial and ovarian cancer in those women. The majority of cancers were observed during the first five years of tamoxifen treatment whereas the few cancers found in the anastrozole-treated group were found post-treatment.
There was a non-significant trend to more GI and lung cancers in the anastrozole group.
“We observed a significant 34% increase in fractures in women who received anastrozole compared to tamoxifen and we also observed a three-fold increase in stroke and TIA with anastrozole compared to tamoxifen [OR 3.1].”
“Although the PEs and DVTs were higher in the tamoxifen arm, they were statistically not significantly different compared to in those randomised to anastrozole.”
The study did not observe a significant difference between the two drugs for any cause of death.
“In conclusion, there is really no significant difference in recurrence between anastrozole and tamoxifen.”
She said the study did not confirm the late effect of a 27% reduction in recurrences with anastrozole as seen in the 2016 NSABP B-35 trial after a median of nine years of follow-up.
“We did however observe very clear differences in adverse events between anastrozole and tamoxifen.”
“So although our analysis did not show any significant difference in terms of recurrence between anastrozole and tamoxifen, it really shows that an improved understanding about adverse effect profiles helps patients with DCIS to make an informed decision regarding their treatment.”
Dr Nicholas Zdenkowski, Breast Cancer Trials Medical Advisor and Study Chair of IBIS-II, said adverse events were an especially important consideration when choosing therapies for preventative purposes.
“This trial shows that both drugs are safe to take, with notable differences in the side effects,” he said.
“This knowledge can assist with guiding patients towards which drug is more suitable for their personal circumstances. It is hoped that anastrozole will be listed on the PBS for prevention purposes, given the favourable safety and effectiveness profile.”
Study disclosures: Co-investigators on the study Dr Jack Cuzick has received research grants and Dr Anthony Howell has received honoraria and speaker’s fees from AstraZeneca.
[Editor’s note: This article story has been amended to remove a comment made by International Co-Chair for the IBIS-II DCIS clinical trial, Professor John Forbes, as it referred to a previous meeting of SABCS].