Addition of Stereotactic Body Radiation Therapy to Systemic Therapy Improves Outcomes Among Patients With Oligometastatic, Oligoprogressive NSCLC

At the Great Debates and Updates in Lung Cancer Meeting in New York, New York, Charles Simone, MD, Memorial Sloan Kettering Cancer Center, New York, New York, argued that adding stereotactic body radiation therapy (SBRT) to systemic therapy is a strong and effective way to treat patients with oligometastatic or oligoprogressive non-small cell lung cancer (NSCLC). 

Dr Simone states, “We need more data but clearly, we see data, including randomized data in both the oligometastatic and the oligoprogressive setting, that radiation therapy, particularly SBRT, can improve outcomes.” 

Transcript: 

Hi, my name is Dr Charles Simone, I'm a research professor and the Chief Medical Officer at the New York Proton Center. I'm also a full member in the Department of Radiation Oncology at Memorial Sloan Kettering. Today, I'm talking about the role of local therapy, particularly stereotactic body radiation therapy (SBRT) in patients with oligometastatic and oligoprogressive disease. My stance is that there is a strong role for these modalities.

We know, unfortunately, the majority of patients with lung cancer present with stage 4 disease and we also know that while there have been improvements in systemic therapy, whether it's immunotherapies and targeted therapies, ultimately patients are going to progress with the primary tumor being a common site of progression. We also know that progression at the primary tumor in stage 4 patients leads to higher rates of brain metastases and other distant metastatic disease and directly impacts overall survival. While systemic therapy is improving, it's actually more important than ever to control the primary tumor. 

There have now been several randomized trials, albeit small, mostly phase 2, showing that the addition of radiation therapy to systemic therapy versus systemic therapy alone can actually improve outcomes. In fact, there have been several randomized trials that have been terminated early based on data safety monitoring analysis, showing a significant benefit to the addition of radiation to systemic therapy alone. Most of those trials have actually shown a tripling of the progression-free survival if you add SBRT to systemic therapy versus systemic therapy alone, so a clear, clear benefit. Certainly, we need more data, larger data, but consistently now across a half dozen trials in non-small cell lung cancer, there's a benefit to the radiation in the oligometastatic setting. 

What about in the oligoprogressive setting? Now this is also a critical population, especially in the targeted patients that are getting an ALK-/EGFR-directed therapy where unfortunately when they start to progress even in one site, they may need to switch therapies and lose that potential benefit of that well-established targeted therapy. SBRT can have a great role in treating isolated local areas of progression, allowing patients to have control of that area and stay on their systemic therapy leading to longer times without needing to switch agents, ultimately fewer side effects, and better overall survival. 

There's a large, randomized trial published just earlier this year in Lancet, showing that in patients with oligoprogressive disease, with non-small cell lung cancer, when comparing systemic therapy alone to systemic therapy with SBRT to sites of oligoprogression, patients did a lot better with the addition of SBRT, and not a little bit, this is a 4-and-a-half-fold increase in progression-free survival and event-free survival in patients getting radiation compared with those that did not. We don't have survival data from that trial yet, I'm sure with a 4-and-a-half-fold improvement in progression, we're going to see a clear survival benefit as well. 

Here too we need more data but clearly, we see data, including randomized data in both the oligometastatic and the oligoprogressive setting, that radiation therapy, particularly SBRT, can improve outcomes. The other exciting part to mention is we're seeing increasing ways that SBRT and immunotherapy can be synergistic together. Everything from the abscopal effect to other ways to make immunotherapy work more effectively. That's a horizon that we still need a lot of research in but it is another exciting avenue when considering SBRT in the oligometastatic and oligoprogressive settings.

Source: 

Simone C. Debate: Oligoprogression or oligo-remnant mNSCLC: Local ablative approaches is standard: Yes vs no. Presented at Great Debates & Updates in Lung Cancer; April 27-28, 2024; New York, NY.