Maintenance systemic therapy versus local consolidative therapy plus maintenance systemic therapy for NSCLC

Dr Puneeth Iyengar - Memorial Sloan Kettering Cancer Center, New York, USA

On behalf of the NRG Oncology LU002 team, I would be happy to present the main findings from our trial. The trial asked a very important question – in the setting of oligometastatic non-small cell lung cancer, so advanced non-small cell lung cancer, does radiation therapy and/or surgery as local consolidative therapy impact progression free survival when added to maintenance systemic therapy. Really the question in this randomised phase II/III study is can we find a set of patients with advanced non-small cell lung cancer where local therapy can help improve survival outcomes. So that was the main purpose of this study.

The eligibility of this study were patients with oligometastatic non-small cell lung cancer after first line systemic therapy. They then got randomised to maintenance systemic therapy alone or radiation and/or surgery followed by maintenance systemic therapy. The primary endpoint was to see the impact of that treatment, additional local treatment, on progression free survival. After a one- and two-year follow-up what we found was that there was really no difference between the two treatment arms, the control arm and the experimental arm, with respect to progression free survival. There was no difference with respect to overall survival and there may have been a little bit of increased toxicity with the use of the experimental arm.

At the moment in time the study suggests that we should not routinely use radiation with systemic therapy to manage oligometastatic non-small cell lung cancer patients but there may be case-by-case evaluations that may offer a rationale for doing so.

What could be the impact of this research?

For the longest time historically radiation was used purely for palliation – palliation from bleeding, palliation from obstructive symptoms in the lungs, palliation from disease that was encroaching on neurologic tissue that would cause neurologic compromise. Then, again, over the last three decades there was an impetus to start using radiation to improve overall survival, progression free survival.

So the study does not demonstrate an improvement in progression free or overall survival in this current era of immunotherapy-based systemic therapy. But we are still doing subset analyses and we may find subsets of oligometastatic non-small cell lung cancer patients where there was an enrichment and benefit with the use of local therapy. That is yet to be done but in this current iteration of our evaluations there’s probably no big obvious benefit with the use of radiation in patients who are receiving immunotherapy.

We thought that this study would be the end all and be all but, in many ways, this study is just another important study in the evolution of our understanding of how to optimise different therapies in different stages of lung cancer. As we now know, in every stage of lung cancer, 1, 2, 3 and 4, we are using surgery, we are using radiation and we are using systemic therapy. So the real question becomes in the future how do we integrate all of these different therapies. So this was one study in the advanced setting that tried to show a benefit at time of consolidation. This may not be the perfect time to use radiation, maybe radiation is best used up front at the time of diagnosis; maybe it’s best used at oligoprogression. But we still need to do a lot of work but the data gives us a lot of fundamental information about the natural evolution of patients who have oligometastatic disease because those were the patients eligible for the study. So it gives us a very rich dataset for us to understand what is happening to these patients who are receiving multimodal therapy.

The other thing I will say is that we collected blood so we’ll be able to do ctDNA evaluations. We collected quality of life metrics for these patients so we’ll really be able to understand or hopefully identify a predictive biosignature which shows which patients would have benefitted and which ones would not have benefitted from local therapy and can use that for future trials.