The addition of ovarian suppression to tamoxifen lengthened OS and DFS among premenopausal women with breast cancer, according to updated findings from the TEXT and SOFT trials published in The New England Journal of Medicine.
Results — which were published in correspondence with a presentation at the ASCO Annual Meeting on freedom from distant metastases data from the trials — also showed exemestane plus ovarian suppression resulted in higher rates of freedom from recurrence.
“Adjuvant treatment with tamoxifen for 5 years reduces the recurrence of premenopausal ER-positive breast cancer, with increasing benefits for OS during 5 to 15 years of follow-up,” Prudence A. Francis, MD, head of medical oncology in the breast service at Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues wrote. “Extending the duration of tamoxifen treatment to 10 years further improves outcomes. The effect of adding ovarian suppression has been less certain.”
The researchers performed a prespecified updated analysis of the SOFT and TEXT trials. In the SOFT trial, researchers randomly assigned women to receive tamoxifen alone (n = 1,021), tamoxifen plus ovarian suppression (n = 1,024), or exemestane plus ovarian suppression (n = 1,021). In the TEXT trial, researchers randomly assigned patients to tamoxifen (n = 1,334) or exemestane (n = 1,338), both with ovarian suppression. In both studies, women received treatment for 5 years.
Previously reported results showed 5-year rates of breast cancer recurrence were significantly
lower among premenopausal women who received exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. However, the addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates.
After a median follow-up of 8 years, in the SOFT study, 8-year DFS was 83.2% among those assigned tamoxifen plus ovarian suppression compared with 78.9% among women assigned tamoxifen alone (HR = 0.76; 95% CI, 0.62 to 0.93). Among patients assigned exemestane plus ovarian suppression, 85.9% achieved 8-year DFS, for a difference of seven percentage points compared with tamoxifen alone (HR = 0.65; 95% CI, 0.53 to 0.81)
Eight-year OS was 93.3% with tamoxifen plus ovarian suppression group compared with 91.5% in the tamoxifen group (HR = 0.67; 95% CI, 0.48 to 0.92). The difference with exemestane plus ovarian suppression compared with tamoxifen alone did not reach statistical significance (92.1%; HR = 0.85; 95% CI, 0.62-1.15).
Among women who remained premenopausal after chemotherapy, 8-year OS was 89.4% with tamoxifen plus ovarian suppression compared with 85.1% with tamoxifen alone (HR = 0.59; 95% CI, 0.42 to 0.84). For exemestane plus ovarian suppression, 8-year OS was 87.2% (HR vs. tamoxifen alone = 0.79; 95% CI, 0.57-1.09).
Among women with HER-2-negative disease who underwent chemotherapy, 8-year OS was 85.2% among patients assigned tamoxifen alone, 87.7% among those assigned tamoxifen plus ovarian suppression (HR vs. tamoxifen = 0.7; 95% CI, 0.48-1.02), and 88.7% among those assigned exemestane plus ovarian suppression (HR vs. tamoxifen = 0.71; 95% CI, 0.49-1.05).
After a median follow-up of 9 years for 4,690 patients in the combined TEXT and SOFT population who received ovarian suppression, 8-year DFS was 86.8% among patients assigned exemestane plus ovarian suppression and 82.8% among those assigned to tamoxifen plus ovarian suppression (HR = 0.77; 95% CI, 0.67 to 0.9).
The 8-year rate of freedom from distant recurrence was 91.8% for exemestane plus ovarian suppression and 89.7% for tamoxifen plus ovarian suppression (HR = 0.8; 95% CI, 0.66-0.96).
In the HER-2-negative chemotherapy cohorts, 8-year rate of freedom from distant recurrence was higher among those assigned exemestane plus ovarian suppression than tamoxifen plus ovarian suppression (SOFT, by 7 percentage points; TEXT, by 5 percentage points).
Approximately one-fourth of women assigned tamoxifen alone experienced grade 3 or higher adverse events (24.6%), compared with 31% of those in the tamoxifen plus ovarian suppression group and 32.3% in the exemestane plus ovarian suppression group.
“Longer follow-up is planned for SOFT and TEXT, [because] data regarding survival and late adverse events are immature,” the researchers wrote.
Francis and colleagues noted that in other studies, “maximal separation of Kaplan-Meier curves for OS has typically occurred more than 10 years after randomization,” and that in one recent study, distant metastases occurred as long as 20 years following diagnosis.
“After a median follow-up of 8 years or 9 years, the effects of ovarian suppression and aromatase inhibitors may not yet be fully appreciated,” Francis and colleagues wrote. – by Andy Polhamus
Francis PA, et al. N Eng J Med. 2018;doi:10.1056/NEJMoa1803164.
Regan MM, et al. Abstract 503. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Francis reports travel reimbursement from Pfizer, as well as honoraria from AstraZeneca and Novartis outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.