SABR Evidence Summaries - Oligometastatic and Oligoprogressive disease

Radiotherapy has been around for over 100 years, but it doesn't stand still. The last decade has seen a rapid expansion in the role of highly targeted ablative radiotherapy, which is aimed at eradicating tumours with minimal collateral damage through an entirely non-invasive and convenient treatment course. In 2015, the use of stereotactic ablative radiotherapy (SABR) in the United Kingdom was almost entirely confined to the treatment of small, inoperable primary lung cancers. An innovative programme in the National Health Service (NHS) saw this expanded to the treatment of oligometastatic disease, a situation in which there is limited spread from a primary tumour to other organs, and where randomised trial evidence has shown there is the realistic prospect of long-term cancer control in many patients when used alongside standard-of-care drug therapy. At GenesisCare we saw the potential of the MRIdian platform - a combination of an MRI scanner with a radiotherapy machine, which allows us to target tumours with next-level precision - to take the treatment of oligometastatic disease in new directions.

Our MRIdian programme has now treated over 600 private and NHS patients across our two centres, in Oxford and London. We're immensely proud of our team of doctors, physicists and radiation therapists, all of whom are focussed on achieving the best possible clinical outcomes for people with metastatic cancer. Some of that experience is summarised in our new publication, Evidence Summaries in Oligometastatic and Oligoprogressive Disease, which we hope you enjoy. We're also proud to have delivered MRI-guided SABR to 50 NHS patients with pancreatic cancer during the COVID-19 pandemic, when they had few if any other options for active treatment, and to have fully funded a trial at the University of Oxford looking at shortening the treatment course from five to one session, further increasing the potential for patient benefit.

Until recently, data on the use of SABR for oligometastases was predominantly limited to single-arm and observational studies. The SABR-COMET (Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases) trial represents a significant addition to the literature as the first randomised controlled trial to compare outcomes of SABR plus standard of care with standard of care alone in oligometastatic disease. Long-term results published in 2020 demonstrated significant improvement in outcomes for patients treated with SABR:

• 99 patients with one to five metastases
• Randomised 1:2 to receive standard of care (SOC) or SOC plus SABR
• Initial results published in 2019 and long-term results in 2020
• Median overall survival benefit of SABR 28 months (22 months in the SOC arm vs. 50 months in the SOC plus SABR arm)
• 5-year overall survival of 17.7% in the SOC arm vs. 42.3% in the SOC plus SABR arm
• Safety: generally well-tolerated with a favourable toxicity profile. Three Grade 5 adverse events (possible treatment-related deaths) were reported in the SOC plus SABR arm.

The treatment benefits of SABR demonstrated in SABR-COMET paved the way for further Phase III trials. SABR-COMET is now being followed up by two further Phase III trials: SABR-COMET-3 and SABR-COMET-10, investigating treatment outcomes following SOC plus SABR in patients with 1-3 and 4-10 metastases, respectively.

SABR-COMET-3

• Enrolling 297 patients
• Comparing SOC vs. SOC plus SABR in patients with 1-3 metastases
• Started Nov 2019, study due to complete Dec 2028

SABR-COMET-10

• Enrolling 159 patients
• Comparing SOC vs. SOC plus SABR in patients with 4-10 metastases
• Started Feb 2019, study due to complete Jan 2029.

Since March 2020, SABR has been available through the NHS for patients with oligometastatic disease, limited to patients with metachronous oligometastatic disease and no more than three metastases (with the exception of synchronous colorectal liver metastases that meet other criteria). The NHS commissioning policy was based on an Evidence Review and a Commissioning through Evaluation (CtE) study. In this single-arm study, 1,422 patients with 1-3 metastases were treated with SABR. Overall survival was better than estimated at 92.3% at one year (compared with a prediction of 70%) and 79.2% at two years (compared with a prediction of 50%). The toxicity profile was favourable and there were no treatment-related deaths reported.

Evidence for the impact of SABR on outcomes is growing. Key published studies include:

• STOMP – 62 patients with prostate cancer plus 1-3 metastases. Improved survival was demonstrated in patients treated with either surgery or SABR to ablate metastases.
• ORIOLE – 54 patients with prostate and 1-3 metastases. Showed lower rate of progression in patients treated with SABR compared with observation. No toxic effects grade 3 or above observed.
• Maintenance chemotherapy vs. SABR + maintenance chemotherapy for Stage IV NSCLC – 29 patients with 1-5 metastases. Trial stopped early after interim analysis found significant improvement in progression-free survival in patients treated with SABR (9.7 months) followed by maintenance therapy vs. maintenance therapy alone (3.5 months).
• Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients with Oligometastatic Non-Small-Cell Lung Cancer – 49 patients with Stage IV NSCLC plus 1-3 metastases. The study closed early after interim analysis showed progression-free survival of 14.4 months in patients treated with surgery or SABR vs. 3.9 months with maintenance therapy / observation.

Further research into SABR treatment is ongoing. Key trials include:

• CORE – 245 patients with breast, prostate or NSCLC plus 1-3 metastases (Phase II / III, ongoing)
• PACE – 2,290 patients with prostate cancer and no metastases – Phase III. PACE-B results show no difference in acuate GI and GU toxicity between SABR and conventional radiotherapy.
• SARON – 340 patients with NSCLC and 1-5 metastases (Phase III, ongoing)
• HALT – 110 patients with NSCLC (Phase II / III, ongoing)

The encouraging Phase II data from SABR-COMET has provided further support to the growing body of evidence indicating improved patient outcomes following treatment of oligometastases with SABR. Combined with rapidly developing practical experience of treatment, SABR is increasingly becoming a treatment option of choice. Whilst further data are awaited to build on the understanding of the clinical application of SABR treatment, access to those patients able to benefit from it should be supported. GenesisCare is committed to offering the highest standards of care in treating all patients with cancer, as well as continuing to recognise the importance of patient choice.

GenesisCare is recognised as a centre of excellence for SABR treatment in the independent sector and is one of the providers leading the advancement of this treatment in the UK. The GenesisCare service is guided by a team of expert clinicians with extensive experience in delivering SABR for all tumour types. Patient selection is a key determinant of successful outcomes. Our focus is on:

• Improving patient outcomes
• Improving patient experience and quality of life
• Patient choice

We’re committed to helping build the body of evidence for SABR, notably through our partnership with the University of Oxford to increase trial access to MRI-guided SABR. As a patient-centric organisation, we are also motivated by the opportunities SABR presents to improve patient experience and quality of life. We have a twice-weekly SABR MDT to discuss potential cases and our SABR Advisory Team can provide informal advice and assistance in assessing whether SABR might be a suitable treatment for individual patients.

To read our full evidence summary for SABR in oligometastases, download the SABR Innovations Journal (Oligometastases Edition). This comprehensive evidence summary contains relevant case studies across all tumour groups and a range of SABR approaches, from simple to complex and MRI-guided.

Find out more about SABR at GenesisCare here.