Metastasis-directed therapy fails in oligometastatic breast cancer

Metastasis-directed therapy, either stereotactic ablative radiotherapy (SART) or surgical resection, added to standard-of-care did not provide a significant clinical benefit over standard-of-care alone for patients with oligometastatic breast cancer, according to the results of the phase 2R/3 NRG-BR002 trial.

The phase 2 SABR-COMET trial (NCT01446744) displayed a clinical benefit of SART for patients with oligometastatic cancers [1]. “In oligometastatic breast cancer, phase 3 data for the efficacy of metastasis-directed therapy is lacking,” mentioned Dr Steven Chmura (University of Chicago, IL, USA). The phase 2R stage of the phase 2R/3 NRG-BR002 trial (NCT02364557) randomised 128 patients with oligometastatic breast cancer 1:1 to first-line, standard-of-care systemic therapy with or without additional metastasis-directed therapy (surgical resection or SART) [2]. Previously, the phase 1 NRG-BR001 trial demonstrated the absence of dose-limiting toxicities for the use of SART in patients with multiple metastasis [3]. Progression-free survival (PFS) was the primary endpoint of the current study.

In total, 93% of the patients in the experimental arm received SART and only 2% received surgery. After a median follow-up of 35 months, no significant difference was measured in PFS between the 2 treatment arms (HR 0.92, P=0.36). The 36-month PFS rates were 32.8% in the control arm and 38.1% in the experimental arm, which were not sufficient enough to continue with the phase 3 part of the trial.

Both treatment arms were well tolerated and showed similar safety profiles. In the control arm, 10% of the patients had a grade 3 adverse event, whereas 5% of the patients in the experimental arm experienced a grade 3 adverse event. Only 1 grade 4 adverse event was reported, which occurred in the control arm. Finally, exploratory data showed that patients with >1 metastasis may benefit more from additional metastatic-directed therapy, whereas those with 1 metastasis may be better off with the standard-of-care alone.

“High dose SART was safe in patients with oligometastatic breast cancer, but this metastasis-directed therapy failed to provide a significant PFS benefit for these patients,” concluded Dr Chmura.

1. Palma DA, et al. J Clin Oncol. 2020;38:2830‒2838.
2. Chmura SJ, et al. 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). Abstract 1007, ASCO 2022 Annual Meeting, 3‒7 June, Chicago, IL, USA.
3. Chmura S, et al. J Clin Oncol. 2021; 7(6):845‒852.

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Posted on 5 August 2022