CHICAGO — Extending aromatase inhibitor therapy for 5 years beyond an initial 5 years resulted in a 34% reduction in recurrence without worsening quality of life in postmenopausal women with early-stage breast cancer, according to study results presented during the plenary session of the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.1
“Women with early-stage hormone receptor-positive breast cancer face an indefinite risk of relapse,” said lead study author Paul Goss, MD, FRCP, PhD, director of breast cancer research at Massachusetts General Hospital in Boston, MA, and professor of medicine at Harvard Medical School.
Therefore, researchers sought to evaluate the risk of recurrence after 10 years of aromatase inhibitor therapy in a randomized, open-label, phase 3 trial. For the study, investigators enrolled 1918 postmenopausal women who had received 5 years of any 1 of 3 aromatase inhibitor therapies as either initial therapy or after prior tamoxifen. Patients were randomly assigned 1:1 to receive letrozole or placebo, with 90% beginning treatment within 6 months of completing prior therapy.
Patient-reported quality of life was measured using the standard Short Form 36 (SF-36) questionnaire, as well as a menopause-specific questionnaire, MENQOL. Of the 1428 patients eligible to complete initial quality-of-life assessments, which were repeated at 12, 24, 36, 48, and 60 months, more than 85% of women completed the questionnaires at follow-up.
At a median follow-up of 6.3 years, there was a 34% reduction in recurrences with letrozole compared with placebo (HR, 0.66; P=.01). Further, researchers observed a 58% reduction in contralateral breast cancer with letrozole (HR, 0.42; P=.007); however, there was no significant difference in overall survival between the 2 treatment arms.
“The study provides direction for many patients and their doctors, confirming that prolonging aromatase inhibitor therapy can further reduce the risk of breast cancer recurrences,” said Dr Goss. “Longer aromatase inhibitor therapy also showed a substantial breast cancer preventative effect in the opposite, healthy breast.”
Additionally, no new emergent symptoms or toxicities were observed. There was also no worsening of quality of life in either group.
“Bone fractures (14% vs 9%; P=.001) and new-onset osteoporosis (11% vs 6%; P<.0001) were significantly more frequent in the letrozole arm,” Dr Goss noted.
“Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore our results will further improve the outcome of many women with breast cancer,” Dr Goss concluded.
However, invited discussant for this abstract Ian E. Smith, MD, consultant medical oncologist and professor of cancer medicine at The Royal Marsden NHS Foundation Trust in London, England, questioned the significance of the difference in bone toxicity, noting that the difference is not large numerically, and these adverse events are preventable with bisphosphonates.
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In addition, Dr Smith pointed out that a reduction in contralateral breast cancer contributes significantly to the disease-free survival benefit.
“The difference is only 1.1% so far for distant recurrence and there is so far no significant survival benefit,” Dr Smith said. “These data do not justify telling all of our patients to continue letrozole beyond 5 years, but in a patient with high-risk features who has thrown off unpleasant early side effects, I would discuss the data and help them make a choice.”
- Goss PE, Ingle JN, Pritchard K, et al. A randomized trial (MA. 17R) of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer. J Clin Oncol. 2016; 34 (suppl; abstr LBA1).