NRG-BR002: A phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557).

1007 Background: Prospective and retrospective studies of patients (pts) with oligometastatic (OM) disease have supported that metastases (mets) directed treatment (MDT) with SBRT or SR in addition to standard of care systemic therapy (SOC ST) can improve progression-free (PFS) and overall survival (OS) compared with SOC ST alone. However, randomized evidence in oligometastatic breast cancer (OMBC) are lacking. NRG-BR002, a randomized Phase IIR/III trial, sought to determine the efficacy of SOC ST + MDT (SBRT or SR) as first line treatment of OMBC. Methods: OMBC pts with ≤ 4 extracranial mets on standard imaging with controlled primary disease were eligible if on first line SOC ST for ≤ 12 months without progression. Pts were randomized (1:1) to ARM 1 – SOC ST (mainly chemotherapy, endocrine therapy, anti-HER2) or ARM 2 – SOC ST with MDT of all mets. Stratification included mets number (1 vs > 1), ER/PR and Her2 status, and chemotherapy use. Phase IIR targeted sample size was 128 total/116 eligible pts, for 92% power and 1-sided significance level = 0.15 to determine if adding MDT shows a signal for improved PFS (hazard ratio [HR] = 0.55, corresponding to median PFS (mPFS) from 10.5 to 19 months), in order to continue to the full phase III trial for OS. PFS and OS were estimated by Kaplan-Meier and arms compared with log-rank. Results: 125 of the 129 pts randomized were eligible (ARM 1 = 65, ARM 2 = 60). Key characteristics included median age 54, 79% ER+ or PR+/HER2-, 13% HER2+, 8% triple negative. 60% had 1 metastasis and 20% presented synchronously with primary disease. Following randomization, systemic therapy was delivered to 95% in ARM 1 and 93% in ARM 2; ablation: SBRT 93%, SR 2%, and 5% none. The median follow-up was 30 mo. The mPFS (70% CI) in ARM 1 was 23 mo (18, 29) and 19.5 mo (17, 36) in ARM 2; 24 and 36-mo PFS (70% CI) for ARM 1 were 45.7% (38.9, 52.5) and 32.8% (26.0, 39.5) compared with 46.8 (39.2, 54.3) and 38.1 (29.7, 46.6) in ARM 2; HR (70% CI): 0.92 (0.71, 1.17); and 1-sided log-rank p = 0.36. As PFS did not show signal, OS reporting is included: median OS was not reached in either arm; 36-mo OS (95% CI) in ARM 1 71.8% (58.9, 84.7) and ARM 2 68.9% (55.1, 82.6; 2-sided log-rank p = 0.54). Analysis of first failure showed new mets outside index area (Arm 1) /RT field (Arm 2) developed similarly in both arms at 40%. There were fewer new mets inside treated/index area for Arm 2 6.7% vs ARM 1 29.2%, respectively. There were no grade 5 treatment-related adverse events (AEs), 1 grade 4 AE in ARM 1, and 9.7% and 5.3% grade 3 AEs in ARMS 1 and 2, respectively. Circulating tumor cell counts (0 vs ≥1) at baseline were similar in both arms and were not prognostic HR (95% CI): 1.04 (0.54, 2.02). Conclusions: The addition of MDT to SOC ST did not show signal for improved PFS, nor OS difference in patients with OMBC. The trial will not proceed to the Phase III component. Clinical trial information: NCT02364557.