Michael D. Mix, MD
Stereotactic body radiation therapy (SBRT) has been a mainstay in the treatment of patients with early-stage non– small cell lung cancer (NSCLC), explained Michael D. Mix, MD, and results of a randomized phase II trial have confirmed its utility in patients with oligometastatic disease, as well.
“It has long been questioned whether or not aggressive local therapy to distant metastatic sites in NSCLC, as well as in other cancers, is worthwhile,” Mix said. “It’s exciting to see results showing that [this approach] can play a fairly important role in improving overall survival (OS) in addition to progression-free survival (PFS) in oligometastatic NSCLC.”
To be eligible for enrollment in the phase II trial, patients had to have 3 or fewer metastatic lesions. Those who did not progress after receiving frontline chemotherapy or targeted therapy were randomized to receive aggressive management with either surgery or radiation, with or without chemotherapy, or to receive standard-of-care chemotherapy or observation. Results were presented at the 2018 ASTRO Annual Meeting and showed median OS rates of 41.2 months and 17 months at 38.8 months of follow-up in the local consolidative arm and the standard-of-care arm, respectively.
As the trial began prior to the introduction of immunotherapy in the lung cancer space, additional randomized trials will be needed to verify these results.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Mix, assistant professor of radiation oncology at Upstate University Hospital, discussed the use and optimization of SBRT in the management of patients with early-stage NSCLC and oligometastatic NSCLC.
OncLive: How has SBRT been used in the management of patients with NSCLC?
I focused my presentation on the use of SBRT in 2 settings: early-stage NSCLC and oligometastatic NSCLC. In early-stage NSCLC, I highlighted the high levels of local control we’ve been able to achieve over the last 10 to 15 years and noted some ways that we can improve those outcomes, particularly in regional disease in distant failures. Then I discussed the use of SBRT in [patients with] oligometastatic NSCLC and attempted to figure out whether or not the addition of SBRT to standard systemic therapy [can improve] outcomes in these patients. [Based on available data], it seems that it might be able to.
What is the role of this therapy in early-stage disease?
In early-stage NSCLC, SBRT is widely used in patients who are considered medically inoperable or in those who refuse surgery. [With this approach, we are able to] obtain high local control rates, greater than 90%. However, some patients are at risk for failing either regionally, within the lymph nodes, or with distant metastases. These are the patients we are most concerned about. Despite our close surveillance, some patients will fail despite our best efforts. If we can better identify which patients will fail, perhaps we will be able to offer additional therapies or catch their disease progression sooner.
How is this approach used in a patient with oligometastatic disease?
If we treat metastases aggressively, can we improve the patient’s overall prognosis? [This approach is] something that has been [used] in practice for quite some time, but we’ve been lacking definitive evidence. [In my presentation], I highlighted one of the first prospective studies, which is the only randomized prospective trial to date that has demonstrated that we may be able to improve not only PFS but also OS with the addition of aggressive local therapy. Generally, this is in terms of [applying] SBRT to 3 or fewer sites of metastases.
Could you speak to the findings of that trial?
The trial was presented at the 2018 ASTRO Annual Meeting by Daniel Gomez, MD, of The University of Texas MD Anderson Cancer Center. It was a multi-institution, randomized, phase II trial that enrolled patients with 3 or fewer metastases after 4 cycles of standard systemic therapy. Patients were randomized to receive either standard-of-care maintenance or observation, or aggressive local therapy, which they called local consolidative therapy. The trial showed a significant and durable benefit in PFS. What’s exciting about the recent results is the fairly robust OS benefit. Patients who received SBRT showed a median OS of 41 months.
How does radiotherapy fit into the context of a multidisciplinary treatment approach?
Patients with NSCLC are best managed in a multidisciplinary fashion. That means the involvement of surgeons, medical oncologists, pulmonologists, radiologists, and, of course, radiation oncologists. Radiation oncologists play a pivotal role in [treating] patients with all stages of NSCLC. In stage I, we can achieve high rates of local control in patients who aren’t good candidates for surgery. We can offer adjunctive therapy before or after surgery in patients with stage II or III disease or in patients who aren’t surgical candidates. We can provide definitive management along with systemic therapy for patients with stage III disease. In patients with a small burden of stage IV metastatic disease, radiation oncologists will likely become more involved in the treatment of metastases, now that we’ve seen the suggestion of improvement in overall prognosis.
Gomez DR, Tang C, Zhang J, et al. Local consolidative therapy (LCT) improves overall survival (OS) compared to maintenance therapy/observation in oligometastatic non–small cell lung cancer (NSCLC): final results of a multicenter, randomized, controlled phase 2 trial. In: Proceedings from the 2018 American Society for Radiation Oncology Annual Meeting; October 21-24, 2018; San Antonio, Texas. Abstract LBA3.