Background
Combined analysis of the TEXT and SOFT trials. 4,690 premenopausal women with HR+ early breast cancer, all receiving ovarian function suppression (OFS), randomized to exemestane+OFS vs tamoxifen+OFS to test whether an aromatase inhibitor improves outcomes over tamoxifen.
Interventions and follow up
Arm A: Exemestane 25mg daily + OFS
Arm B: Tamoxifen 20mg daily + OFS
OFS achieved by GnRH agonist triptorelin 3.75mg IM q28d, bilateral oophorectomy, or bilateral ovarian irradiation.
Primary endpoint: DFS
mFollow up: 68mo (~5.6yr)
Arm B: Tamoxifen 20mg daily + OFS
OFS achieved by GnRH agonist triptorelin 3.75mg IM q28d, bilateral oophorectomy, or bilateral ovarian irradiation.
Primary endpoint: DFS
mFollow up: 68mo (~5.6yr)
Results
5-yr DFS, AI+OFS vs TAM+OFS: 91.1% vs 87.3% (HR 0.72, 95%CI 0.60-0.85, P<.001).
5-yr freedom from breast cancer: 92.8% vs 88.8% (HR 0.66, 95%CI 0.55-0.80, P<.001).
5-yr freedom from distant recurrence: 93.8% vs 92.0% (HR 0.78, 95%CI 0.62-0.97, P=.02).
OS: 95.9% vs 96.9%, no benefit (HR 1.14, 95%CI 0.86-1.51, P=.37).
5-yr freedom from breast cancer: 92.8% vs 88.8% (HR 0.66, 95%CI 0.55-0.80, P<.001).
5-yr freedom from distant recurrence: 93.8% vs 92.0% (HR 0.78, 95%CI 0.62-0.97, P=.02).
OS: 95.9% vs 96.9%, no benefit (HR 1.14, 95%CI 0.86-1.51, P=.37).
Adverse events
Musculoskeletal/bone: arthralgia, myalgia, and osteoporosis more frequent with exemestane+OFS.
Vasomotor: hot flashes common in both arms (OFS effect).
Gynecologic/thrombotic: vaginal symptoms, thromboembolism more frequent with tamoxifen+OFS.
Psychiatric: depression in both arms.
Overall: grade 3-4 AEs ~31% (exemestane+OFS) vs ~29% (TAM+OFS); profile resembled AI therapy plus OFS-related menopausal symptoms.
Vasomotor: hot flashes common in both arms (OFS effect).
Gynecologic/thrombotic: vaginal symptoms, thromboembolism more frequent with tamoxifen+OFS.
Psychiatric: depression in both arms.
Overall: grade 3-4 AEs ~31% (exemestane+OFS) vs ~29% (TAM+OFS); profile resembled AI therapy plus OFS-related menopausal symptoms.
Conclusions
Among premenopausal women receiving OFS, exemestane reduced recurrence vs tamoxifen, with no OS difference. Benefit is most relevant for higher-risk patients (stage II-III, high-risk biology), particularly women <35yr.
Key Limitations
No OS benefit at 5.6yr; HR+ disease recurs late, requiring longer follow-up. All patients received OFS, so it does not address OFS vs no OFS. Pooled SOFT+TEXT design with differing chemotherapy use; menopausal toxicity affects adherence.
Clinical Context
Established exemestane+OFS as a preferred option for higher-risk premenopausal HR+ breast cancer. ASCO and ESMO guidelines support AI+OFS in this setting. Updated 12-yr SOFT/TEXT data confirm a sustained DFS and distant-recurrence benefit with an emerging OS signal favoring exemestane+OFS.
References
Pagani O et al, NEJM, 2014; PMID: 24881463
Francis PA et al, NEJM, 2018 (SOFT/TEXT update); PMID: 29863451
Francis PA et al, NEJM, 2018 (SOFT/TEXT update); PMID: 29863451