In this interview, Luke Pike, MD, Memorial Sloan Kettering Cancer Center breaks down the TURBO-Non–Small Cell Lung Cancer (NSCLC) study, which examined patient outcomes for patients with EGFR- and ALK-driven NSCLC with brain metastases who were treated with central nervous system (CNS)-penetrant TKIs with or without upfront stereotactic radiosurgery (SRS).

Could you please introduce yourself by stating your name, title organization, and relevant professional experience?

Hi, my name is Luke Pike, and I am part of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center. I'm the director of Brain Radiation Oncology where I lead a group that takes care of patients with brain tumors, both in primary and secondary causes. I personally lead a research group that focuses on better understanding how to manage patients with brain metastases and understand the biology of the disease.

What led you and your colleagues to conduct this study?

The TURBO study was initially put together by Chad Rusthoven, MD, at the University of Colorado, and I took over leadership of the study later on. The underlying issue facing patients with NSCLC is that they are highly prone to developing brain metastases. In particular, patients with EGFR and anaplastic lymphoma kinase (ALK) mutant, or ALK-altered disease, are even more prone, so it's a common situation that we encounter in clinical practice.

Historically, we treated everybody with brain metastasis upfront with radio surgery or, prior to that, whole brain radiation. But in more recent years, we've seen the development of CNS-active drugs that could potentially reduce the frequency in which we need to treat these patients. And so, there's been a growing trend toward using drug therapy alone without radiation therapy for patients with EGFR mutant and ALK fusion positive disease. But that’s never been tested in a head-to-head fashion—radiation plus drug vs drug alone. In that modern context we sought to better understand what the actual outcomes of those patients are when they're followed longitudinally. And so, we put together a large cohort study of 317 such patients to better describe their outcomes.

What were the study methods?

This was a retrospective cohort study that involved seven academic medical centers from across the US, all of whom have a deep level of expertise and knowledge around the management of patients with NSCLC brain metastasis.

Each group pooled their data on patients who are fully treatment naive to TKIs and had newly diagnosed brain metastases. They had also either underwent an initial treatment strategy of TKI alone or TKI plus upfront radio surgery. We looked at those patients' outcomes with a primary endpoint of time to intracranial failure.

Can you summarize the main findings of your study?

When we looked at the overall cohort of 317 patients, a couple of key things jumped out at us. First, the patients who had received upfront TKI alone had a lower disease burden, while those who had received upfront radio surgery in addition to the TKI tended to have larger metastases that were more likely to be symptomatic at the time of diagnosis.

For the primary endpoint of time to intracranial progression, we found is that when we looked at All-Comers there was no statistical significant difference. However, when we adjusted for the extent of disease (the size of the largest brain metastasis), we found a strong effect that favored upfront radio surgery over TKI alone. The patients who had received radio surgery were far less likely to have their disease progress later.