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It has been hypothesised that successful ablation of oligometastatic disease (OMD) may improve survival outcomes. Stereotactic body radiation therapy (SBRT) is an advanced radiotherapy technique that can deliver ablative doses to OMD. Previous studies have shown SBRT is safe & effective in locally controlling disease in this setting, but there are few randomised data to allow evaluation of the true benefit of adding SBRT to standard of care (SOC) therapy.  CORE, a phase 2/3 trial, aimed to demonstrate 1) feasibility of recruitment, 2) study deliverability in a multicentre setting & 3) activity of SBRT based on progression-free survival (PFS). If all three aims were achieved the trial would be expanded into parallel tumour-site specific phase 3 trials.

CORE (NCT02759783) randomised (1:1) patients (pts) with breast, prostate or non-small cell lung primary cancer & ≤3 metachronous OMD sites, who are systemic therapy naïve in the metastatic setting, to SOC +/- SBRT.  SBRT dose & fractionation was dependent on OMD site.  SOC was declared pre-randomisation & could include chemotherapy, biological therapy, hormone therapy or observation at investigator’s discretion.  Palliative radiotherapy could also be given in SOC only arm. Primary endpoint was PFS (all 3 primary disease site cohorts analysed together in ITT population). For phase 2, a sample of 242 pts was required based on a median PFS estimate of 16 months for SOC, 80% power, alpha 0.2 (1-sided; signal finding), hazard ratio (HR)=0.75 & 5% lost to follow-up.  A minimum of 50 pts per cohort was targeted.

Between 11/2016-02/2019 245 pts were randomised (180 prostate, 40 breast, 25 lung; 121 SBRT+SOC, 124 SOC) from 21 UK & 9 Australian centres. Median follow-up was 42.5 months (IQR: 35.9-48.8). Median age was 69 years; 153 (62%) pts had 1 OMD site at baseline, 92 (38%) had 2+. In SBRT+SOC, 116/121 (96%) received SBRT. 164/245 (67%) pts completed SOC as planned; this proportion differed by treatment group (62% SBRT+SOC vs 75% SOC, p=0.002). Overall PFS (HR=0.79 (95%CI: 0.57-1.09), p=0.16 in favour of SBRT+SOC; median PFS=25.0 months for SBRT+SOC, 19.9 months for SOC.  In the per protocol population (n=184; excluding pts who did not have SOC as planned & ineligible pts) PFS HR=0.73 (95%CI: 0.50-1.06); p=0.10.

Overall, the trial met its phase 2 objectives & identified a PFS signal in favour of SBRT+SOC justifying larger definitive phase 3 randomised trials; although recruitment rate in breast & lung cohorts would suggest a trial re-design is required to ensure timely delivery.  Despite lack of level 1 evidence, SBRT has become an accepted treatment option for OMD & despite good recruitment to the prostate cohort in phase 2, the trial did not graduate to phase 3. However, biomarker rich & biologically informed randomised trials are still essential to define the group of pts who benefit from SBRT.