Comprehensive Stereotactic Ablative Radiotherapy (SABR) for Oligometastatic Solid Tumors: Long-Term Overall Survival, Progression-Free Survival, Safety, and Quality-of-Life Results From the SABR-COMET Phase II Randomized Trial

Abstract

Purpose: The oligometastatic cancer paradigm proposes that patients with a limited number of metastatic lesions may achieve long-term disease control, or potentially cure, when all known sites of disease are ablated. Long-term randomized evidence evaluating this approach has been limited. Methods: Patients with a controlled primary malignancy and 1-5 metastatic lesions were enrolled if all metastases were amenable to stereotactic ablative radiotherapy (SABR). Participants were stratified by number of metastases (1-3 v 4-5) and randomly assigned in a 1:2 ratio to palliative standard-of-care (SOC) treatments (arm 1) or SOC plus comprehensive SABR to all metastatic lesions (arm 2). This randomized phase II screening trial used overall survival (OS) as the primary end point, with an α of .20, where P < .20 indicated a positive trial. Secondary end points were progression-free survival (PFS), toxicity, and quality of life (QOL). Long-term trial outcomes are reported. Results: From 2012 to 2016, 99 patients were randomly assigned at 10 international centers. The most common primary tumor types were breast cancer (n = 18), lung cancer (n = 18), colorectal cancer (n = 18), and prostate cancer (n = 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% with SOC alone in arm 1 (95% CI, 6% to 34%) versus 42.3% with SOC plus SABR in arm 2 (95% CI, 28% to 56%; stratified log-rank P = .006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years, with the last patient censored) and was 17.3% in arm 2 (95% CI, 8% to 30%; P = .001). No new grade 2-5 adverse events occurred, and QOL did not differ between treatment arms. Conclusion: With extended follow-up, adding comprehensive SABR to palliative SOC produced an OS effect that was larger in magnitude than in the initial analysis and remained durable over time. No new safety signals were observed, and SABR did not have a detrimental impact on QOL. Trial registration: ClinicalTrials.gov NCT01446744.