Treating EGFR+ NSCLC Brain Metastases


Benjamin Levy, MD: The brain metastases story I think is a nice story here and the ability to elicit meaningful responses in the brain with a therapy that’s well tolerated. Is there a cutoff where you think, well, this patient needs to see radiation oncology rather than get a next-generation TKI [tyrosine kinase inhibitor]?

D. Ross Camidge, MD: You mean before, instead of just relying on the TKI therapy first?

Benjamin Levy, MD: Correct. Is there a tipping point, Bob, where you think, well, you know what, there’s a lot of edema, there’s some neurological compromise?

Robert Doebele, MD, PhD: We work really closely with our radiation oncologist on this question. In fact, Chad Rusthoven, MD, one of our radiation oncologists, and I wrote an editorial on this. I think for asymptomatic brain metastases, I’m perfectly fine and so are the radiation oncologists going with a brain penetrant TKI first with follow-up monitoring to make sure that the brain metastases are shrinking as expected. I think the cutoff for me is extremely symptomatic disease, although that can be controlled with steroids and other measures. I’m thinking there that we start steroids, maybe start the TKI, but also send them to the radiation oncologist. They can get that treated while they’re on osimertinib, and that’s not a concern really.

Benjamin Levy, MD: Your comfort level is OK with using both, the osimertinib while they’re getting radiation therapy.

Robert Doebele, MD, PhD: Yes.

Benjamin Levy, MD: OK.

D. Ross Camidge, MD: It’s partly an artificial scenario because if they’re newly diagnosed with horribly symptomatic brain metastases, you don’t have that molecular back and they can’t sit around and wait for 2 weeks. It’s really the scenario where you happen to know that molecular information and they land in your lap.

Joshua Bauml, MD: But I’ve also had cases where patients had locally advanced disease. I know their molecular profile because I’m doing the testing on those patients as well. And then they present with metastatic disease, including brain metastases. What I’ve done is I’ve spoken with the neurosurgeon, spoken with the radiation oncologist. I say, “Look, is it pushing on something that’s going to be dangerous, do we have a little bit of wiggle room?” And if they say yes, then I start the TKI and we go from there. And I’ve seen very nice responses when we’ve done that. I will say when we give the TKI at the same time as the SRS [stereotactic radiosurgery], I believe there’s a slightly increased risk for radionecrosis. It’s not a substantial increase, but it’s something we need to be aware of.

Zofia Piotrowska, MD: I don’t think we have a lot of great data on that specifically with osimertinib. And it’s always a worry with the more CNS [central nervous system] penetrant drugs. But usually I think if you hold it you just have to hold it right around the time of the radiation.

Robert Doebele, MD, PhD: Yes. The other message I think that’s really critical is avoiding whole brain radiotherapy, right.

Benjamin Levy, MD: If at all possible.

Robert Doebele, MD, PhD: These are patients who often are going to live 3, 4, 5, 8 years, and we want to avoid that. And so those are situations, even if the patient is symptomatic, even if they have 25 brain metastases and we know that they have a CNS penetrant TKI option, I want to give that patient the drug, then reimage and see what we need to treat to mop up that disease. But we’ve seen significant toxicity, long-term cognitive toxicity, in our patients who get whole brain radiotherapy early. And I think we should be delaying that in every patient.

Zofia Piotrowska, MD: Absolutely. I think even SRS is not a complete freebie. There is a risk of radiation necrosis. And again, for these patients who are living a long time who may have multiple sites treated over time, that can also become a problem. I think that like you, we have a very close relationship with our radiation oncologist, and many of these patients will meet the radiation oncologist, and we’ll follow them together, so that we can make decisions based on the MRI [magnetic resonance imaging]. But I think many of our radiation oncologists now know that these drugs are so CNS penetrant that they also feel very comfortable foregoing radiation up front and monitoring closely.

Benjamin Levy, MD: I think there’s a call for communication.

Zofia Piotrowska, MD: Absolutely.

Benjamin Levy, MD: Given the drugs that we have and to make sure that the players are all on the same playing field in terms of understanding how to optimize treatment strategies for these patients.

Zofia Piotrowska, MD: Even before the molecular testing comes back. If you have a patient who sees radiation oncology, calling them and saying, “Hey, let’s wait for this testing to come back before we decide whether to give radiation and what kind of radiation because there’s a chance we may have something better and less toxic to offer.”

Joshua Bauml, MD: I think having a multidisciplinary team in this setting is essential, and talking and making sure you have a good relationship with your colleagues to make sure that you can talk about these topics. No one is trying to compete here, right? Everyone is trying to help the patient and make sure they get the best possible outcome. I think that’s essential.

Benjamin Levy, MD: I think it’s important. We used to historically think of multidisciplinary teams for stage III patients, integrating the surgeons and radiation oncologists. But with the advent of targeted therapy and the toxicities, even immunotherapy, the call for communication.

Zofia Piotrowska, MD: And local consolidative therapy, there are so many opportunities for collaboration.

Transcript Edited for Clarity

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