CLINICAL INVESTIGATION
Stereotactic Radiation for the Comprehensive Treatment of Oligometastases (SABR-COMET): Extended Long-Term Outcomes

https://doi.org/10.1016/j.ijrobp.2022.05.004Get rights and content

Purpose

Long-term randomized data assessing the effect of ablative therapies in patients with oligometastases are lacking. The Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases (SABR-COMET) randomized phase 2 trial was originally designed with 5 years of follow-up, but the trial was amended in 2016 to extend follow-up to 10 years. Herein we report oncologic outcomes beyond 5 years.

Methods and Materials

Patients were eligible if they had a controlled primary tumor and 1 to 5 metastases, with all metastases amenable to SABR. Patients were randomized in a 1:2 ratio between palliative standard-of-care treatment (control arm) versus SABR to all metastases plus standard of care (SABR arm). The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), toxicity, quality of life (using the Functional Assessment of Cancer Therapy: General [FACT-G]), and time to new metastases.

Results

Ninety-nine patients were randomized between 2012 and 2016 (n = 33 in arm 1 vs n = 66 in arm 2). Primary tumor sites included lung (n = 18), breast (n = 18), colon (n = 18), prostate (n = 16), and other (n = 29). Eight-year OS was 27.2% in the SABR arm versus 13.6% in the control arm (hazard ratio, 0.50; 95% confidence interval, 0.30-0.84; P = .008). Eight-year PFS estimates were 21.3% versus 0.0%, respectively (hazard ratio, 0.45; 95% confidence interval, 0.28-0.72; P < .001). Rates of grade ≥ 2 acute or late toxic effects were 30.3% versus 9.1% (P = .019), with no new grade 3 to 5 toxic effects. FACT-G quality of life scores declined over time in both arms, but there were no differences in quality of life scores between arms. The use of systemic therapy overall was similar between arms, but patients in the SABR arm were less likely to require cytotoxic chemotherapy (33.3% vs 54.6%, respectively, P = .043).

Conclusions

SABR achieved durable improvements in OS and PFS, with no new major toxicity signals with extended follow-up. A minority of patients randomized to the SABR arm (21.3%) achieved > 5 years of survival without recurrence.

Introduction

Several randomized controlled trials (RCTs) have now assessed the use of SABR or hypofractionated radiation therapy (RT) in patients with oligometastatic cancers. Although these RCTs have mostly used phase 2 designs (or were phase 3 trials that did not complete), many have shown improvements in overall survival (OS), progression-free survival (PFS), or other endpoints, across a number of cancer histologies.1, 2, 3, 4, 5 However, median follow-up from these prior trials remains short. Long-term outcomes after SABR in patients with oligometastases have not yet been examined in randomized trials.

Long-term outcomes from randomized trials are important to assess potential late toxic effects (in light of the large hypofractionated doses delivered with SABR, with their attendant risk of late effects) and to determine whether improvements in OS and PFS remain durable with time. The Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases (SABR-COMET) study was a randomized trial assessing SABR in patients with a controlled primary tumor and 1 to 5 oligometastases and completed accrual in 2016. Before initial analysis of data from the trial, the follow-up duration was extended from 5 to 10 years to better capture long-term outcomes and potential late effects. Here we report outcomes after a minimum potential follow-up of 5 years in all patients.

Section snippets

Methods and Materials

SABR-COMET was a phase 2 randomized trial conducted in 10 centers in Canada, Scotland, the Netherlands, and Australia. Trial details and 2 reports have been previously published.2,6,7 Briefly, patients were required to have a controlled primary tumor (for at least 3 months) with evidence of 1 to 5 metastases. All patients were > 18 years of age, with Eastern Cooperative Oncology Group performance status 0 to 1. Patients with serious medical comorbidities or those where the site of metastases

Results

Over a period of 5 years (February 2012 to August 2016), 99 patients were randomized (n = 66 in the SABR arm and n = 33 in the control arm) across 10 centers. Baseline characteristics are shown in Table 1, and a CONSORT diagram is provided in Figure E1.

Median follow-up was 5.7 years (95% confidence interval [CI], 5.1-7.0). The primary outcome event, death from any cause, occurred in 40/66 (60.6%) in the SABR arm and 25/33 patients (75.8%) in the control arm, with 8-year OS estimates of 27.2%

Discussion

In this report, we present the 8-year follow-up data from the SABR-COMET trial, which to our knowledge represents the longest follow-up data from an RCT of SABR for oligometastatic disease. Although there is no standard definition of cure across disease sites, these data show that based on actuarial estimates, approximately 1 in 5 patients in the SABR arm achieved survival beyond 5 years without recurrence or progression, which may be tantamount to cure for some histologies. These 8-year data

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This study was presented as a late-breaking abstract at the European Society for Radiotherapy and Oncology 2022 Annual Meeting in May 2022.

This study was funded by the Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.

Disclosures: S.H. has received honoraria from AstraZeneca, Pfizer, and Takeda Pharmaceuticals, has consulted for AstraZeneca, and has received travel, accommodations, and expense reimbursements from AstraZeneca and Takeda Pharmaceuticals, unrelated to the current study. D.P. receives research funding from the Ontario Institute for Cancer Research and is a consultant with Equity for Need Inc, unrelated to the current study. R.O. has received grant funding from Varian Medical Systems and is a consultant with Equity for Need Inc, unrelated to the current study. A.L. has received honoraria for advisory board and speaking engagements from AstraZeneca, Varian Medical Systems, and Reflexion Medical, unrelated to the current study. M.L. has consulted for Sanofi Canada and has participated in a speaker's bureau for Ferring and AbbVie, unrelated to the current study. D.S. has received honoraria from AstraZeneca, Merck, and Pfizer and has received research funding from Varian Medical Systems, unrelated to the current study. B.A. has consulted for Ferring, AbbVie, and Genentech, unrelated to the current study. A.S. has received honoraria from Bristol Meyers Squibb and has consulted for AstraZeneca, unrelated to the current study. G.B. has received honoraria from Bayer AG, unrelated to the current study. S.S. has received honoraria from AstraZeneca, BeiGene, Varian Medical Systems, and MSD Oncology, has consulted for AstraZeneca, Celgene, Varian Medical Systems, and MSD Oncology, has participated in a speaker's bureau for AstraZeneca, and has received research funding from ViewRay, AstraZeneca, and Varian Medical Systems, unrelated to the current study.

Data sharing statement: The trial protocol did not include a data sharing plan; therefore, data from the trial will not be shared publicly as sharing was not included in the ethics approvals.

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