Evaluating Stereotactic Radio Surgery Plus TKI Vs TKI Alone Among Patients With Brain Metastases from EGFR- and ALK-Altered NSCLC (Part II)

In this interview, Luke Pike, MD, Memorial Sloan Kettering Cancer Center, shares key takeaways from 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). He also discusses promising studies on the horizon for EGFR mutant NSCLC treatment.

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 (MSK) 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 key takeaways from the study would you like to highlight?

The primary endpoint was time to intracranial progression, which we found was positive. However, we did not find an effect on overall survival. So, as it stands right now, especially without prospective clinical trial data to guide us, I don't believe that we should jump to change clinical practice in a major way. However, it should give pause because what we found is that patients who got the drug alone, especially those with bigger tumors, really did have a lot higher rate of failure in the brain. And those failures were usually in the place that they had the original disease.

In a given patient, it's worth a more nuanced conversation about whether or not to pursue drug alone or drug plus radio surgery. For example, someone who has a bulkier brain metastasis in the motor strip or in another eloquent area of the brain where a failure—even if it doesn't cause death—could result in significant neurologic morbidity. And so, I would advocate for both radiation oncologists as well as thoracic medical oncologists to take pause at this data and consider what might be best for the particular patient in front of them.

Are there any promising studies on the horizon for the treatment of EGFR mutant NSCLC?

Many clinical trials and studies, including ours, have looked at clear end points such as whether or not the disease came back and whether or not that resulted in the loss of life, such as overall survival difference. But in the brain, far more so than other parts of the body, having a progression event is meaningful. That's where there's a greater need for further studies to evaluate this effect to confirm in a prospective clinical trial setting. What we do for a given patient has to be a balance between when to treat, how to treat, and the potential consequences of taking one approach over the other.

At MSK we are putting forth and are in the process of approval of a prospective clinical trial that aims to address a novel approach altogether. Instead of treating everybody with radio surgery up front or nobody with radio surgery at diagnosis, we make use of the fact that these drugs work for the vast majority of patients and allow patients in all cases to get drug therapy initially for a window of about three months, such that the disease has an opportunity to respond.

If we see that their brain metastases have shrunken down and disappeared completely, then we can probably safely avoid radio surgery in that patient without any great consequence and therefore have potentially de-escalated treatment overall for that patient in a safe manner. This will also reduce the likelihood of them having sequela of treatment such as radionecrosis, which is something that we are always concerned about. This design also allows for identification of the worst actors. And so, in that trial we're going to do upfront drug therapy.

The patients who do not have a complete response and more likely to have disease failure will be randomized to either continue surveillance very closely with treatment at the time of progression or to treatment at that end time point with what we're calling consolidative radio surgery. The study is called ICONRT, which is intracranial consolidation for EGFR mutant NSCLC brain metastases.