Patient-Reported Symptoms Can Inform Advice on Tamoxifen Versus Anastrozole

“Patricia

Patricia A. Ganz, MD

A new study has shown that overall quality of life is similar among patients taking tamoxifen or anastrozole, but patient reports on their hot flashes, night sweats, vaginal dryness, and joint pain can help illuminate which therapy may be right for a particular woman. And, the analysis shows, age matters.

The findings, based on a secondary analysis of the phase III NSABP B-35 trial, mark an important step toward the goal of “personalizing medicine for the whole patient,” remarked Patricia A. Ganz, MD, presenting the findings during a press conference at the San Antonio Breast Cancer Conference (SABCS).¹ The results were also published online December 10 in the Lancet.

NSABP B-35 was a double-blind, placebo-controlled trial that compared the efficacy of 5 years of tamoxifen versus anastrozole in reducing breast cancer recurrence in women treated with lumpectomy and radiation for their HR-positive DCIS. The study enrolled 3104 women, and results reported at the 2015 ASCO Annual Meeting showed that although both agents proved effective on the study’s primary outcome measure of time to any breast cancer event, anastrozole was found to be slightly better than tamoxifen in terms of breast cancer—free interval and most beneficial in women younger than 60 years.²

At SABCS, Ganz, director of the UCLA Jonsson Comprehensive Cancer Center’s Prevention and Control Research program, reported findings on patient-reported outcomes (PROs), a secondary endpoint of NSABP B-35. The findings are based on the responses of 1193 participants to validated measures of PROs used in prior breast cancer prevention trials. In addition to assessing their overall quality of life, women taking tamoxifen (n = 601) or anastrozole (n = 592) were asked to report on specific symptoms, such as hot flashes, vaginal dryness, and muscle and joint pain.

These data were collected over 5 years, with questionnaires issued at baseline and every 6 months thereafter. Data for an additional 12 months have not yet been analyzed, Ganz noted. The women across both treatment arms were divided fairly evenly by age, with slightly more women aged ≥60 years (n = 633); 12% of participants were nonwhite.

On the measure of overall quality of life, investigators found no difference between women in the tamoxifen and anastrozole groups on either their physical or mental component scores using the SF-12 tool (P = .02 and P = .38, respectively) over the 5 years of analysis. “There was no change in either physical functioning or mental functioning as women took either of these two drugs,” said Ganz.

Symptom Frequency Differs

Results on specific bothersome symptoms revealed some difference in PROs for the two medications, however. After 6 months of therapy, the frequency of hot flashes increased with both drugs in both older and younger women, and was “a tad worse” in the tamoxifen group, Ganz reported. Vaginal dryness also went up with both tamoxifen and anastrozole, but more significantly with anastrozole.

“Over 60% of the women entering the trial at baseline had musculoskeletal complaints and joint pain,” Ganz noted. “This is very common in postmenopausal women.” These complaints did rise after 6 months of adjuvant therapy—by 10% in the tamoxifen group and about 20% with anastrozole.

Ganz also discussed severity of symptoms, which she said provides a better picture of women’s experience with both of the drugs. On a 1-5 severity scale, with 5 being the most severe, Ganz stressed that vasomotor and musculoskeletal symptoms remain between 1 and 2 on average after treatment with either of the two therapies. “We’re talking about modest severity of symptoms. Even though they may be frequent, they’re not that severe.”

Shortly after starting the drugs, a composite of hot flash and night sweat scores did go up (P = .0105), but also diminished over time in both treatment arms, Ganz explained. The musculoskeletal pain composite score (joint pain, muscle aches, and general aches and pains) went up in both treatment groups, but more so with anastrozole (P = .0006), and Ganz said, “[these complaints] do not really subside significantly; they stay up over time.”

Investigators had expected sexual functioning would be worse with anastrozole, but the results did not bear this out. Although sexual functioning was worse than average in both groups, there was no difference in sexual functioning scores between the two arms, a finding which was sustained over the 5 years of the trial (P = .56).

Side Effects More Severe in Younger Women

Stratifying results by age may help clinicians to advise their patients on which adjuvant approach may be better for them, Ganz said. For example, “not only are vasomotor symptoms worse in patients treated with tamoxifen, they are significantly greater in younger women [<60 years]…This might be a symptom that would be important to think about in younger women with tamoxifen.”

Although no difference overall was seen between the two therapies with respect to worry over weight (something Ganz noted was a concern among menopausal women generally), and not just breast cancer survivors, “younger women significantly reported greater difficulty with weight gain and being unhappy with their appearance”; no difference was reported between the two treatment arms, Ganz said. This trend was also true across both arms with regard to vaginal symptoms in younger women, but these were worse with anastrozole, Ganz noted. Likewise, gynecologic problems (eg, discharge, itching) were worse in younger women in both arms, “but again, very low severity,” Ganz added.

“With this kind of information on patient-reported outcomes…physicians and patients can now make much more personalized decisions about which of these two effective agents they should select,” Ganz concluded.

1. Ganz PA, Cecchini RS, Julian TB, et al. Patient-reported outcome (PRO) results, NRG Oncology/NSABP B-35: a clinical trial of anastrozole vs tamoxifen in postmenopausal patients with DCIS undergoing lumpectomy plus radiotherapy. Presented at: San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX.

2. Margolese RG, Cecchini R, Julian TB, et al. Primary results, NRG Oncology/NSABP B-35: a clinical trial of anastrozole versus tamoxifen in postmenopausal patients with DCIS undergoing lumpectomy with radiation. J Clin Oncol. 2015;33 (suppl; abstr LBA500).