Management of Cancer That Has Spread to the Brain - Episode 15
Priscilla Brastianos, MD: At what point do we talk to patients about clinical trial enrollment? Please talk a little bit more about what are the risks and benefits of participating in clinical trials.
Raymond Sawaya, MD: Clinical trial enrolment is crucial for many reasons. One important reason is it is shown that patients who enter clinical trials generally do better, maybe because they get much more attention, closer follow-up, and care. It’s not clear, but it is shown that they do better. Number 2, unfortunately, there are still too many questions that we have not answered, and to be able to advise a patient as to which treatment is superior and in what circumstance, that requires a clinical trial. It’s very important to have those trials available for patients.
Number 3, in terms of patients accepting a clinical trial, the overwhelming majority of patients will agree to enter a trial. The problem is when we present a patient with two options that are so different one from the other, they may not accept having a computer decide which way to go. As an example, we had a clinical trial comparing surgery with radiosurgery for brain metastasis because we wanted to show which patients will do better, depending on the size, etcetera. Well, half of the patients refused to enter the trial because it was comparing an invasive procedure with a noninvasive procedure. It’s very important for us, when we design a trial, to find equipoise, to find situations that are fairly similar, so that it’s not too hard on the patient to make the decision.
Vinai Gondi, MD: All patients, I believe, should have an opportunity for clinical trials, whether they have brain metastases or not, patients with any type of cancer. That’s good not just for that patient, but it’s good for the community of oncology and the future patients who come through our doors. But in the area of brain metastases, there are so many questions that remain unanswered. When we think about clinical trials—for instance, systemic therapy trials for patients with brain metastases—where we run into challenges oftentimes is that we’ve treated a lesion with radiotherapy and really don’t have any other options from a radiotherapy perspective because of the risk of causing harm. That’s where there’s tremendous opportunity to use drug therapy in those situations. But even preceding that, it becomes important to evaluate those drug therapy scenarios in a situation very similar to Ivy’s, where we have some time to watch these lesions and see how the systemic therapy works. In Ivy’s case, it was a remarkable success and that’s fantastic. In other cases, it may not be, but that’s OK because we can follow it, we can catch them early, before they cause symptoms. I do think, from a systemic therapy perspective, as a radiation oncologist who manages these patients, it’s always something that I’m considering. Do I need to treat right now, and if I don’t, is there a systemic therapy off-trial that’s available or on-trial that allows us to help this patient delay time to radiotherapy and perhaps help the next patient coming through the door?
From a radiotherapy trial perspective, we’re doing a lot of trials in this area to continue to improve our technology and our ability to safely treat patients using these modalities that I spoke about earlier. One of the unique aspects of the radiotherapy trials that we’ve done in the brain metastases sphere, is that, thanks to our patients and their caregivers, they have been some of the fastest accruing clinical trials I’ve ever been a part of, and that speaks to our patient population—that they’re so interested in trying to help us move the field forward and take care of patients.
Priscilla Brastianos, MD: I want to add to that point. It’s incredibly generous of patients like Ivy and Katie to participate in clinical trials. It’s inspiring and heroic because you’re often first getting to trials where you don’t know that there’s going to be a benefit for you. But you’re doing this to help others and that’s moving to see patients who are so generous with that. What are the benefits? You have access to potentially novel therapy that can help you. There are risks because it is a novel therapy, so we don’t know what the side effects are. It’s incredibly important for the field and for other patients and we thank you and we’re grateful to you, Katie and Ivy, and other patients, that you’re participating in these trials.
I can speak a little bit more to some of the systemic therapy trials. Dr. Ahluwalia already mentioned some of the targeted therapies that people are looking at. Now there are novel targets that people are discovering, particularly even in patients with brain metastases. There are a number of targeted therapies that are showing great promise in different histologies. For example, in breast cancer, tucatinib is a HER2 [human epidermal growth factor receptor 2] agent that shows activity in brain metastases, and then in lung cancer, we’re seeing promising results with EGFR inhibitors, with RET inhibitors such as selpercatinib and pralsetinib, with MET inhibitors such as capmatinib, and now there are KRAS inhibitors that are being investigated in clinical trials. We also have a genomically guided brain metastases trial that’s national right now, that’s open at more than 300 hospitals throughout the United States, and we have three drug arms to that study. We have a PI3 kinase inhibitor arm, we have an NTRK arm, and we have a CDK inhibitor arm, with the goal to add more arms in the coming months and years. With that trial, we’re genetically screening tumor samples from the brain and from extracranial sites that were taken out as part of clinical care, and then if a patient has that specific mutation, they receive that particular inhibitor.
We’re trying to get it open at as many sites, particularly even out in the community too, so that other patients can have access to it. There are a number of current clinical trials, and we hope that patients will have access to those trials.
Transcript Edited for Clarity