Extended hormone therapy prolongs DFS, maintains quality of life
CHICAGO — Extending aromatase inhibitor treatment with letrozole from 5 years to 10 years significantly improved DFS in postmenopausal women with early-stage breast cancer, according to results of the phase 3 trial MA.17R trial presented during the plenary session of the ASCO Annual Meeting.
Further, continued aromatase inhibitor treatment did not appear to compromise overall quality of life, according to an analysis of patient-reported outcomes from the trial.
“Estrogen receptor–positive breast cancer is a chronic and relapsing form of cancer,” Paul E. Goss, MD, PhD, FRCPC, FRCP(UK), director of breast cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School, said during a press conference. “MA.17R asks the question of whether extending aromatase inhibitor therapy from 5 years to 10 years further improves outcomes.”
Postmenopausal women with hormone receptor–positive early-stage breast cancer are usually treated with 5 years of upfront aromatase inhibitor therapy, or with aromatase inhibitors after 2 to 5 years of tamoxifen.
Goss and colleagues evaluated whether extending aromatase inhibitor therapy from 5 years to 10 years could further reduce the risk for breast cancer recurrence.
Benefits of additional therapy
The double blind, randomized controlled MA.17R trial included data from 1,918 women with early-stage breast cancer, whom the researchers randomly assigned to letrozole or placebo for 5 years.
All women enrolled in the trial had previously received 5 years of aromatase inhibitor therapy, either as initial treatment or after tamoxifen.
DFS served as the primary endpoint.
Median follow-up was 6.3 years.
The researchers observed a total of 165 recurrences (letrozole, n = 67; placebo, n = 98). Distant recurrences occurred in 42 women assigned letrozole and 53 women assigned placebo.
Ninety-five percent of women assigned letrozole achieved 5-year DFS 95%, compared with 91% of women assigned placebo. These data equated to a 34% reduced risk for recurrence (HR = 0.66; P = .01).
One hundred deaths occurred on each arm. The 5-year OS rate was 93% for the letrozole arm and 94% for placebo (HR = 0.97).
The annual contralateral breast cancer incidence rate was 0.21% among women assigned letrozole, compared with 0.49% among women assigned placebo. These data represented a 58% reduction in the risk for contralateral breast cancer (HR = 0.42; P = .007).
The researchers did not observe a significant worsening of bone health between groups. A total of 133 bone fractures occurred among women assigned letrozole, compared with 88 in the placebo arm. One hundred and nine cases of new osteoporosis occurred in the letrozole arm compared with 54 in the placebo arm.
Further, researchers did not observe any new emergent symptoms or toxicities.
“MA.17R is the first study to show a benefit of extending aromatase inhibitor therapy beyond 5 years,” Goss said. “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.”
There were no significant differences in overall quality of life or menopause-specific quality of life between the letrozole and placebo arms, according to an analysis of patient-reported data conducted by Julie Lemieux, MD, MSc, of the Centre Hospitalier Universitaire de Québec, and colleagues.
“Aromatase inhibitors decrease estrogen to very low levels in menopaused women,” Lemieux said during the press conference. “Estrogen deprivation can lead to side effects, such as arthralgia, hot flashes and sexual symptoms, such as vaginal dryness.”
Because of these effects, quality of life served as a key secondary endpoint of the trial.
Lemieux and colleagues measured quality of life using the SF-36 questionnaire and the menopause-specific quality of life (MENQOL) survey administered at baseline and every 12 months for up to 5 years. They calculated mean score changes between 12 months and 36 months.
Certain treatment centers required adherence to surveys; at other centers, participation in quality-of-life surveys was optional.
A total of 1,428 patients completed the baseline surveys, and the overall study population had a compliance rate greater than 85%.
Baseline SF-36 summary scores were close to the population norm of 50 and similar in both arms for physical functioning (letrozole, 47.5; placebo, 47.9) and mental functioning (letrozole, 55.5; placebo, 54.8). No significant mean changes occurred over time for physical or mental functioning.
Of the eight remaining subscales of the SF-36 survey, the researchers observed a difference in the role-function physical subscale domain (mean difference, 3.2; P = .009). However, Lemieux noted that this difference did not reach the minimum level of clinical importance, which was 5 points.
Preliminary results suggested that patients randomly assigned to letrozole reported worse vasomotor symptoms (12 months, P = .02; 36 months, P = .03) and sexual functioning (12 months, P = .01; 36 months, P = .01).
However, updated data presented during the press conference showed no difference between the two groups in any of the four domains of the MENQOL questionnaire: vasometer symptoms, psychosocial functioning, physical functioning and sexual functioning.
Lemieux identified limitations of this analysis, including the fact that the population was highly selected. All women studied had tolerated 5 years of aromatase inhibitor therapy, with 70% having also previously received tamoxifen.
“In women who already tolerated 5 years of aromatase inhibitors, extending letrozole did not worsen their global- or menopause-specific quality of life compared with placebo,” Lemieux said. “It is very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life.” – by Cameron Kelsall
Goss, PE, et al. Abstract LBA1. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Lemieux J, et al. Abstract LBA506. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosure: Goss and Lemieux report no relevant financial disclosures. Please see the abstracts for a list of all other researchers’ relevant financial disclosures.