Anastrozole ‘NonInferior’ To Tamoxifen For ER-Positive DCIS

Trial results support the use of anastrozole for postmenopausal patients with oestrogen receptor (ER)-positive ductal carcinoma in situ (DCIS)

medwireNews: Anastrozole offers an alternative endocrine therapy option to tamoxifen for postmenopausal women following surgery for oestrogen receptor (ER)-positive ductal carcinoma in situ (DCIS), suggest results from the IBIS-II DCIS and the NSABP B-35 clinical trials.

The phase III results are published in three articles in The Lancet, including a patient-reported outcomes analysis for the NSABP B-35 trial, and are accompanied by a comment from Stephen Johnston, from the Royal Marsden NHS Foundation Trust in London, UK.

He writes that tamoxifen should remain the treatment of choice for peri- and postmenopausal patients but that aromatase inhibitor therapy may offer greater protection for postmenopausal patients aged less than 60 years.

However, Stephen Johnston notes that the findings do not give “clarity as to which subgroups of patients with ER-positive ductal carcinoma in situ may benefit most” and calls for further research to identify biomarkers that may help direct treatment.

The IBIS-II DCIS study found no significant difference in the outcomes of the 1449 patients randomly assigned to receive anastrozole 1 mg/day for 5 years and the 1489 patients who were given tamoxifen 20 mg/day for the same duration, report Jack Cuzick, from the Wolfson Institute of Preventive Medicine in London, UK, and co-authors.

After a median of 7.2 years, 144 breast cancer recurrences were reported and the rate did not significantly differ between the two treatment groups, thus establishing the aromatase inhibitor as noninferior, but not superior, to tamoxifen.

And the number of patient deaths was comparable between the anastrozole and tamoxifen groups, at 33 versus 36, respectively, with no cause of death particularly associated with either treatment.

Richard G Margolese, from Jewish General Hospital in Montreal, Quebec, Canada, and co-investigators of the NSABP B-35 trial followed up 1552 women randomly assigned to receive anastrozole and 1552 patients randomly assigned to receive tamoxifen for a median of 9.0 years, during which time 212 breast cancer recurrences were reported.

They found that anastrozole offered significantly greater protection against breast cancer recurrence than tamoxifen, with a hazard ratio (HR) of 0.73.

Five-year breast cancer-free survival was achieved by 96.3% of both patient groups but after 10 years there was a divergence in survival with rates of 93.1% for the anastrozole arm versus 89.1% for tamoxifen, a significant difference.

In addition, there was a significant interaction between treatment choice and age, so that anastrozole significantly improved survival over tamoxifen only in women aged less than 60 years.

Nevertheless, the aromatase inhibitor was associated with a significantly lower rate of invasive breast cancer and a reduced risk of both contralateral and invasive contralateral disease compared with tamoxifen use.

The NSABP B-35 quality of life sub-study, by Patricia A Ganz, at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, and co-investigators gives patient-reported outcomes over 5 years for 592 trial participants assigned to receive anastrozole and 601 assigned to receive tamoxifen.

The treatment arms had comparable scores on the 12-item Short Form Health Survey for physical health, mental health, energy and fatigue, depressive symptoms and sexual functioning.

But tamoxifen-treated patients had significantly more severe vasomotor symptoms, difficulties with bladder control and gynaecological symptoms than anastrozole-treated patients, whereas the aromatase inhibitor was associated with significantly more severe musculoskeletal pain and vaginal symptoms.

The researchers note that younger women had more severe vasomotor, vaginal and gynaecological symptoms than older women and were more likely to have weight issues.

“Given the similar efficacy of tamoxifen and anastrozole for women older than age 60 years, decisions about treatment should be informed by the risk for serious adverse health effects and the symptoms associated with each drug”,the researchers write.

“For women younger than 60 years old, treatment decisions might be driven by efficacy (favouring anastrozole); however, if the side-effects of anastrozole are intolerable, then switching to tamoxifen is a good alternative.”

Stephen Johnston concludes: “Overall, both therapies were said to be well tolerated, but the specifics provided by Ganz and colleagues will help clinicians and patients make informed decisions about the relative balance of risks to quality of life and potential benefits in improving breast cancer-free interval.”

References

Fobes JF, Sestak I, Howell A, et al.Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Lancet 2015; Advance online publication 11 December. DOI: http://dx.doi.org/10.1016/S0140-6736(15)01129-0

Margolese RG, Cecchini RS, Julian TB, et al. Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet 2015; Advance online publication 10 December. DOI: http://dx.doi.org/10.1016/S0140-6736(15)01168-X

Ganz PA, Cecchini RS, Julian TB, et al. Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet 2015; Advance online publication 10 December. DOI: http://dx.doi.org/10.1016/S0140-6736(15)01169-1

Johnston S. Endocrine treatments for ductal carcinoma in situ: balancing risks and benefits. Lancet 2015; Advance online publication 11 December. http://dx.doi.org/10.1016/S0140-6736(15)01219-2

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