Data from two clinical trials presented at the San Antonio Breast Cancer Symposium showed that for women with estrogen receptor-positive ductal carcinoma in situ (DCIS), the choice between anastrozole and tamoxifen to lower their chance of post-surgery disease recurrence will likely depend on how their existing conditions relate to side effects from the two drugs rather than efficacy.
The phase III IBIS-II DCIS clinical trial, presented Dec. 11, compared breast cancer recurrence rates in postmenopausal women with DCIS who took either anastrozole or tamoxifen. The phase III NSABP B-35 clinical trial, also presented Dec. 11, compared patient-reported outcomes in two similar patient groups.
The IBIS-II DCIS Trial
Clinical trials conducted previously, including the International Breast Cancer Intervention Study I (IBIS-I) and IBIS-II, showed that both tamoxifen and anastrozole, taken for five years, were effective in preventing breast cancer incidence in women with elevated risk. The protective effects from anastrozole were reported to be higher than those from tamoxifen; however, women in both these clinical trials experienced significant side effects. Women from IBIS-I who took tamoxifen had increased rates of endometrial cancer, lung cancer and nonmelanoma skin cancer, in addition to other side effects. Women in IBIS-II who took anastrozole had more musculoskeletal and vaginal issues and increased hypertension.
Other clinical trials, including the ATAC, showed that aromatase inhibitors were more effective than tamoxifen in preventing recurrence of hormone receptor-positive invasive breast cancer in postmenopausal women. “Given the paucity of data on the effect of aromatase inhibitors on DCIS [stage 0 disease], it was a natural step to explore them for women with DCIS,” says Jack Cuzick, PhD, professor and director of the Wolfson Institute of Preventive Medicine, Queen Mary University of London, who presented the IBIS-II DCIS trial at the symposium.
The trial enrolled 2,980 postmenopausal women with locally excised hormone receptor-positive DCIS to compare the ability of anastrozole and tamoxifen to prevent recurrence (either invasive breast cancer or DCIS). For five years, roughly half of the study participants received 1 mg/day anastrozole and the other half received 20 mg/day tamoxifen. All women also received a placebo that looked like the test drug they did not receive in order to ensure that the side effect profile assessments were reliable.
After a median follow-up of 7.2 years, there were no significant differences in the recurrence rates of invasive cancers and DCIS between the two groups; however, the side-effect profiles were very different.
Women who took anastrozole experienced fewer endometrial and ovarian cancers and skin cancers than women who took tamoxifen. However, more strokes were seen among women taking anastrozole. These women also had more fractures, musculoskeletal issues, and vaginal dryness.
Women who took tamoxifen had more major thromboembolic events and gynecological issues, including hot flashes, vaginal hemorrhage, and discharge, compared with those who took anastrozole.
Although the side-effect profiles were entirely different for women in the two groups, the compliance rates were identical, according to Cuzick. “Anastrozole offers another choice for treating patients with estrogen receptor-positive DCIS. Choice may depend more on tolerability and existing conditions related to side effects than efficacy,” he said.
The NSABP B-35 Trial
The B-35 protocol of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was designed to compare the ability of anastrozole and tamoxifen to prevent disease recurrence in postmenopausal patients with hormone receptor-positive DCIS undergoing lumpectomy with radiation therapy. The trial enrolled 3,104 postmenopausal women, and the results showed that anastrozole was slightly but significantly better than tamoxifen in terms of breast cancer-free interval. It was most beneficial in women younger than 60 years. No overall survival difference was found between the two treatments.
The secondary endpoint of the trial, reported at the symposium, was patient-reported outcomes (PRO), which were based on two measures—quality of life (QOL) and symptom outcomes.
“Because these two drugs have different side-effect profiles, it was important to hear from women about their experiences to add that information to decision making,” says Patricia A. Ganz, MD, distinguished professor at UCLA Schools of Medicine and Public Health and the Jonsson Comprehensive Cancer Center at UCLA, who presented the study at the symposium.
To evaluate QOL, the researchers obtained data from each patient participating in the trial about her experience with the drug in terms of physical and emotional functioning, using the SF-12 Physical Component Summary and Mental Component Summary.
To evaluate symptom outcomes, the researchers measured patient-reported symptoms including hot flashes, vaginal dryness, muscle and joint aches, and pains, using the BCPT Symptom Checklist and other standardized methods.
Ganz reported that there were no differences in QOL outcomes five years after treatment. There were, however, differences in symptom outcomes.
Women who took tamoxifen reported more severe hot flashes than women who received anastrozole, and this experience varied over time. On the other hand, the severity of musculoskeletal pain at six-month to 24-month time points and vaginal problems were greater in those who took anastrozole than in those who took tamoxifen. Sexual functioning was slightly worse for those who took anastrozole compared with those who took tamoxifen.
All symptoms were worse in women younger than 60 years than those 60 years or older, Ganz says.
“Physicians and patients need to use this information along with the main trial outcomes to choose the optimal treatment for each woman. This is part of personalized or precision medicine,” Ganz notes.
Debbi Knauft, a 56-year-old breast cancer survivor and advocate from California, found the results of the two studies interesting and intriguing.
Knauft was diagnosed with invasive breast cancer in 2007. After a lumpectomy and radiation, she took tamoxifen for five years, which caused severe musculoskeletal pain. Her doctors were hesitant to switch her to anastrozole because it is known to cause musculoskeletal pain, and they were concerned that anastrozole could make Knauft’s condition worse. After five years, however, when Knauft switched to anastrozole, her musculoskeletal symptoms had gone down significantly, she says. She continues to take the drug.
“Each woman’s experience with her cancer drug is individual,” Knauft says. These studies underscore the importance of breast cancer patients having an open dialogue with clinicians about the symptoms resulting from their medications, she adds.
“I don’t think many breast cancer patients get enough education about their disease, and so often they feel that there is only one choice,” she says. “I encourage women to participate in clinical trials because having our experiences counted is key to bringing new treatment options.” Knauft is a volunteer for the Breast Cancer Care and Research Fund.
This post is adapted from an article on the website of Cancer Today, a quarterly magazine for cancer patients, survivors, and caregivers published by the AACR. Readall of Cancer Today’s SABCS coverage.
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