Stereotactic ablative radiotherapy for oligometastatic cancers: Efficacy and toxicity results from the randomized SABR-COMET Trial

Abstract

Background: Patients with a limited number of metastases may have a survival benefit if all disease sites are eradicated. We performed a randomized trial to study the impact of stereotactic ablative radiotherapy (SABR) in patients presenting with metachronous oligometastases. Methods: Eligible patients had a controlled primary malignancy with 1‐5 metastatic lesions, all of which were suitable for SABR, had an ECOG performance status 0‐1, and life expectancy >6 months. Stratification was by number of metastases (1‐3 vs. 4‐5). Randomization was in a 1:2 ratio between palliative standard of care (SOC) [Arm 1] vs. SOC plus SABR to all metastatic lesions [Arm 2]. The primary endpoint was overall survival (OS). A randomized phase II screening design was employed with a two‐sided alpha of 0.20 (wherein a p‐value <0.20 designates a positive trial) to provide an initial comparison of the two treatment strategies. Secondary endpoints included progression‐free survival (PFS), toxicity, and QOL (assessed using the FACT‐G). Results: Between 2012‐2016, 99 patients were randomized (33 in Arm 1, 66 in Arm 2) at centres in Canada, Europe and Australia. Median age was 68 (range 43‐89) and the commonest primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18) and prostate (n = 16). Most patients (n = 92) had 1‐3 metastases. Median follow‐up was 26 months. Median OS was 28 months in Arm 1 (95% CI 19‐33 months) vs. 41 months in Arm 2 (95% CI: 26 months to 'not reached'; stratified log‐rank p = 0.09). Median PFS was 6.0 months in Arm 1 (95% CI: 3.4‐7.1 months) vs. 12 months in Arm 2 (95% CI: 6.9‐30 months; stratified log‐rank p = 0.001). Grade ≥2 treatment related adverse events occurred in 9% in Arm 1, and 29% in Arm 2 (p = 0.026). No differences in overall FACT‐G scores were seen at 6 months (mean 82.5 vs. 82.6 respectively; p = 0.992). Rates of related grade ≥ 2 toxicity after SABR were 25% for lung lesions, 31% for bony lesions, 33% for liver and 57% for adrenals (p = 0.45). Lesional control rates after SABR ranged from 100% (in adrenals), 76% (bone), 75% (liver) and 70% (lung), p = 0.56. Conclusions: SABR for oligometastases was associated with an improvement in OS, and a doubling in PFS. Future studies should evaluate techniques to improve lesional control rates.