Updated overall survival results from a randomized phase III trial of non–cross-resistant adjuvant chemotherapy plus endocrine therapy versus endocrine therapy alone in HR+/HER2−/lymph node–positive breast cancer with residual disease following neoadjuvant chemotherapy (NCT01019616).

Abstract

506 Background: Patients with HR+/HER2−, node-positive breast cancer and residual disease after neoadjuvant chemotherapy (NAC) represent a high-risk population yet substantial recurrence risk. Whether additional non-cross-resistant chemotherapy after surgery provides long-term survival benefit beyond endocrine therapy remains uncertain. Our previous analysis of this phase III trial (NCT01019616) with shorter follow-up (median, 72.4 months) did not show a statistically significant survival benefit. Here we report updated survival outcomes with extended follow-up. Methods: Women aged < 65 years with invasive HR+/HER2−, node-positive breast cancer who completed anthracycline-containing NAC and had residual disease (Miller–Payne grade 1–3 and/or residual nodal involvement) were randomized 1:1 to receive either 4 cycles of non-cross-resistant adjuvant chemotherapy plus endocrine therapy (CT+ET) or endocrine therapy alone (ET). The primary endpoint was distant disease-free survival (DDFS); overall survival (OS) was a secondary endpoint. Hazard ratios (HRs) were estimated using Cox proportional hazards models with multivariable adjustment. Results: A total of 379 patients were randomized (CT+ET, n = 187; ET, n = 192) with balanced baseline characteristics. At median follow-up of 135.0 months, 52 deaths occurred: 18 (9.6%) in CT+ET versus 34 (17.7%) in ET. OS was significantly improved with CT+ET (log-rank P = 0.023). Ten-year OS rates were 89.9% versus 82.9% (adjusted HR, 0.56; 95% CI, 0.32–0.99; P = 0.048). DDFS showed a favorable trend ( P = 0.059) with 10-year rates of 85.5% versus 78.3% (adjusted HR, 0.67; 95% CI, 0.41–1.09). Greatest benefit was observed in patients with residual node-positive disease (OS HR, 0.47) and Miller–Payne grade 3 response (OS HR, 0.31). Conclusions: This randomized phase III trial demonstrates long-term overall survival benefit from the addition of non-cross-resistant chemotherapy to endocrine therapy for HR+/HER2−, node-positive patients with residual disease after NAC. Clinical trial information: NCT01019616 .