The recently published long-term results of the SABR-COMET phase II trial have further invigorated treatment options for patients with oligometastatic cancer.1 The early results of the SABR-COMET trial published in April 2019 showed significant promise for stereotactic ablative radiotherapy (SABR) in treating oligometastatic disease, resulting in an OS and a PFS benefit.2 The long-term results of this trial that were recently published help to minimize any lingering doubts about the effectiveness of SABR in treating oligometastatic disease, by demonstrating durable benefit in OS with no additional toxicities.
With an extended median follow-up time from 25 to 51 months in the long-term update, the OS and PFS benefit of SABR were even larger in magnitude than in the initial analysis. Patients treated with SABR had a median OS of 50 months compared to 28 months for those receiving standard of care treatment, including systemic therapy and palliative radiotherapy when indicated; median PFS was 12 months compared to 6 months, respectively. Several of the key criticisms in the initial analysis were addressed, including the fact that the SABR arm had more patients with prostate cancer.3 After a post-hoc sensitivity analysis excluding prostate cancer, the results remained consistent. These results were further supported by two other phase II randomized control trials, which showed an OS and a PFS benefit in patients with oligometastatic NSCLC treated with consolidative SABR and maintenance therapy compared to those treated with maintenance therapy alone.4,5
The SABR-COMET trial now raises the question: What is the extent of oligometastatic disease burden that SABR may benefit? There are ongoing trials examining SABR in treating oligometastatic disease with up to 5 or even 10 metastases.6,7 Although SABR-COMET also included patients with up to 5 metastases, more than 90% of patients had only 1 to 3 areas of metastases. Furthermore, the advent of both immunotherapy and data suggesting synergism between radiation and immunotherapy provide hope for even more promising outcomes with the two combined.8 Several phase I and II trials are ongoing, studying this combination in lung cancer, melanoma, and renal cell carcinoma.9,10
It has long been hypothesized that oligometastatic disease is an “intermediate state,” somewhere between localized disease and widely metastatic disease, and that it is curable with a combination of systemic therapy and local ablative therapies such as SABR.11 The recent publication of the long-term results of the SABR-COMET trial give credence to this idea. Should larger phase III trials demonstrate an OS and a PFS benefit with SABR in oligometastatic disease, we may see a paradigm shift in the way we view oligometastatic disease, as something that is treatable and possibly even curable with SABR. The potential role for radiotherapy in the setting of oligometastatic disease is promising and a key part of the puzzle to help improve outcomes in select patients with metastatic disease.
References:
1. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncol. 2020;38(25):2830-2838.
2. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051-2058.
3. Macbeth F, Treasure T. Points to consider regarding the SABR-COMET trial. Lancet. 2020;395(10222):e19.
4. Gomez DR, Blumenschein GR, Lee JJ, et al. Local consolidative therapy versus maintenance therapy/observation for patients with oligometastatic non-small cell lung cancer without progression after front-line systemic therapy: results of a multi-institutional phase II randomized study. Lancet Oncol. 2016;17(12):1672-1682.
5. Iyengar P, Wardak Z, Gerber DE, et al. Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol. 2018;4(1):1-8.
6. Olson R, Liu M, Bergman A, et al. Population-based phase II trial of stereotactic ablative radiotherapy (SABR) for up to 5 oligometastases: SABR-5. BMC Cancer. 2018;18(1):4-11.
7. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial. BMC Cancer. 2019;19(1):1-15.
8. Ngwa W, Irabor OC, Schoenfeld JD, Hesser J, Demaria S, Formenti SC. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer. 2018;18(5):313-322.
9. Chicas-Sett R, Morales-Orue I, Castilla-Martinez J, et al. Stereotactic ablative radiotherapy combined with immune checkpoint inhibitors reboots the immune response assisted by immunotherapy in metastatic lung cancer: a systematic review. Int J Mol Sci. 2019;20(9):2173.
10. Kang J, Demaria S, Formenti S. Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer. 2016;4:51.
11. Pitroda SP, Khodarev NN, Huang L, et al. Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis. Nat Commun. 2018;9(1):1-8.
