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Exemestane continues to improve DFS, not OS, for early breast cancer
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SAN ANTONIO — Adjuvant aromatase inhibitor exemestane plus ovarian function suppression reduced risk for progression but did not improve OS compared with tamoxifen and ovarian function suppression among women with hormone receptor-positive early breast cancer, according to long-term follow-up results of the combined TEXT and SOFT trials presented at the San Antonio Breast Cancer Symposium.
As HemOnc Today previously reported, an analysis of the trial conducted after a median of 5.7 years showed exemestane plus ovarian function suppression significantly improved DFS compared with tamoxifen plus ovarian function suppression. However, OS data were immature at the time of that analysis.
“Those results have been incorporated into treatment guidelines to help oncologists tailor adjuvant endocrine therapy in this premenopausal patient population,” Prudence Francis, MD, head of medical oncology in the breast service at Peter MacCallum Cancer Centre, said during her presentation. “We report today a planned update after 9 years of median follow-up.”
The TEXT and SOFT trials enrolled women with hormone-positive early breast cancer from November 2003 to April 2011 (TEXT, n = 2,660; SOFT, n = 3,047). Researchers of the TEXT trial randomly assigned women to 5 years of exemestane or tamoxifen — both with ovarian function suppression — with optional chemotherapy, within 12 weeks of surgery.
Researchers of the SOFT trial randomly assigned patients to 5 years of exemestane and ovarian function suppression, tamoxifen and ovarian function suppression, or tamoxifen alone within 12 weeks of surgery if no chemotherapy was planned, or within 8 months of completing neoadjuvant chemotherapy after premenopausal status was re-established.
Ovarian function suppression included 5 years of GnRH agonist triptorelin (Trelstar, Allergan), oophorectomy or ovarian irradiation.
Pagani reported data from a planned update that occurred after the data cutoff of Dec. 21, 2016, and a median follow-up of 9 years.
DFS served as the study’s primary endpoint. Secondary endpoints included invasive breast cancer-free interval, distant recurrence-free interval and OS.
In total, 2,346 patients in the analysis received exemestane and ovarian function suppression, and 2,344 received tamoxifen and ovarian function suppression. Researchers also distinguished between patients who did not receive chemotherapy (TEXT, n = 1,053; SOFT, n = 943), and those who received chemotherapy during TEXT (n = 1,607) or before enrollment on SOFT (n = 1,087).
Twenty-seven percent of patients were aged 40 years or younger, 42% were lymph node positive, 36% had a tumor size larger than 2 cm and 12% were HER-2 positive.
Significantly more patients in the exemestane group achieved 8-year DFS (86.8% vs. 82.8%; HR = 0.77; 95% CI, 0.67-0.9).
Eight-year invasive breast cancer-free interval improved by 4.1% (89.3% vs. 85.2%; HR = 0.74; 95% CI, 0.63-0.87) and 8-year distant recurrence-free interval by 2.1% (91.8% vs. 89.7%; HR = 0.8; 95% CI, 0.65-0.96) with exemestane.
However, OS appeared similar between the arms (8 years, 93.4% vs. 93.3%; HR = 0.98; 95% CI, 0.79-1.22).
Researchers also reported 45 deaths among 1,996 women who did not receive chemotherapy, with a 98% rate of 8-year OS in both arms.
Among 4,035 HER-2-negative patients, researchers reported an HR for OS of 0.86 (95% CI, 0.68-1.1) with exemestane. Larger absolute benefits occurred among patients who received chemotherapy. Researchers also observed a consistent effect by age among the HER-2-negative population, although younger patients demonstrated a greater benefit.
“HER-2-negative and HER-2-positive cancers are now considered clinically relevant subgroups for treatment decision-making,” Francis said. “The HER-2-negative subgroup was the large majority of the trial’s population — 86%. Results for the HER-2-positive subgroup require further investigation.”
A similar proportion of women on both arms experienced grade 3 or grade 4 toxicity (32% vs. 31%), the most common of which included hot flashes, musculoskeletal symptoms and hypertension.
Fifteen percent of patients discontinued therapy early. More patients assigned exemestane stopped endocrine therapy by 4 years (25% vs. 19%), but not triptorelin (18% vs. 19%).
“After longer follow-up, results confirm statistically significant improvements in disease outcomes with exemestane plus ovarian function suppression,” Francis said.
“To ultimately translate absolute trial improvements into clinical practice, oncologists need to discuss and weigh benefits and toxicity in each individual hormone receptor-positive patient,” Francis added. – by Alexandra Todak
Reference:
Pagani O, et al. Abstract GS4-02. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: Francis reports fees from commercial interests from AstraZeneca and has given an overseas lecture for Pfizer. Please see the abstract for all other authors’ financial disclosures.
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Amy H. Comander, MD
The long-term follow-up from the combined analysis of the SOFT and TEXT studies continues to show a significant benefit for use of ovarian suppression along with an aromatase inhibitor over ovarian suppression plus tamoxifen in premenopausal women with early-stage breast cancer, in particular for those higher risk women who received prior chemotherapy.
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