Background
TAILORx. Prospective trial of 9,719 patients with HR+, HER2-negative, node-negative breast cancer (tumor 1.1–5.0cm, or 0.5–1.0cm with unfavorable features) meeting criteria for consideration of adjuvant chemotherapy. By 21-gene Recurrence Score (RS, Oncotype DX) patients were assigned: low (RS ≤10, n=6,711) endocrine therapy alone; high (RS ≥26, n=1,389) chemo-endocrine therapy; intermediate (RS 11–25, n=6,711 randomized) randomized as below.
Interventions and follow up
Arm A: Endocrine therapy alone (RS 11–25)
Arm B: Chemotherapy followed by endocrine therapy (RS 11–25)
Primary endpoint: Invasive disease-free survival (iDFS)
mFollow up: 90mo for iDFS, 96mo for OS
Arm B: Chemotherapy followed by endocrine therapy (RS 11–25)
Primary endpoint: Invasive disease-free survival (iDFS)
mFollow up: 90mo for iDFS, 96mo for OS
Results
9-yr iDFS: 83.3% (endocrine alone) vs 84.7% (chemo-endocrine); HR 1.14, 95%CI 0.99–1.31; P=.06 (noninferior)
9-yr OS: 93.9% vs 93.8%
9-yr freedom from distant recurrence: 94.5% vs 95.0%
Subgroup: Women ≤50yr with RS 16–25 had lower distant recurrence with chemotherapy, with similar OS
9-yr OS: 93.9% vs 93.8%
9-yr freedom from distant recurrence: 94.5% vs 95.0%
Subgroup: Women ≤50yr with RS 16–25 had lower distant recurrence with chemotherapy, with similar OS
Adverse events
Hematologic: Myelosuppression with adjuvant chemotherapy
Neurologic: Neuropathy with chemotherapy
Constitutional: Fatigue with chemotherapy; endocrine-only therapy avoided these toxicities and favored quality of life in low–intermediate RS patients
Neurologic: Neuropathy with chemotherapy
Constitutional: Fatigue with chemotherapy; endocrine-only therapy avoided these toxicities and favored quality of life in low–intermediate RS patients
Conclusions
In HR+, HER2-, node-negative breast cancer with RS 11–25, endocrine therapy alone is noninferior to chemo-endocrine therapy. Chemotherapy may benefit women ≤50yr with RS 16–25. Patients with T1b, low-grade, LVI-negative disease were not enrolled and should receive endocrine therapy alone.
Key Limitations
Node-negative only (RxPONDER addresses 1–3 positive nodes). The age ≤50 / RS 16–25 chemotherapy benefit was an unplanned exploratory subgroup; the mechanism (possible chemotherapy-induced ovarian suppression vs cytotoxic effect) is unresolved. iDFS HR favored chemo-endocrine (noninferiority, not superiority of omission). Predates routine ovarian suppression in this population.
Clinical Context
Practice-defining trial establishing the 21-gene RS as a predictive tool to spare chemotherapy in node-negative HR+/HER2- disease. ASCO and ESMO endorse Oncotype DX for treatment decisions; with RxPONDER (which addresses node-positive disease) these trials anchor genomic-guided chemotherapy de-escalation.
See also RxPONDER (SWOG S1007) trial
See also RxPONDER (SWOG S1007) trial