Personalized Medicine in Lung Cancer


Philippa Cheetham, MD: We’re hearing a lot now in cancer management about personalized medicine, targeted medicine. Thankfully, we’re hearing a lot about research that has led to the development of new drugs to target specific receptors. Can you tell us about mutation testing? What does it mean? What does that mean for the patient, and how does that come into determining how you plan treatment for patients?

Evan C. Osmundson, MD, PhD: As Leora had mentioned, all patients with advanced-stage disease at our facility will get triggered reflex testing for a specific panel of mutations that are actionable mutations, that can have a clinical impact on how we treat the patient. That’s very, very important. From the standpoint of the radiation oncologist, as systemic therapy improves and as patients live longer and longer, local therapy becomes more and more important. And so, there are many patients who have stage 4 lung cancer with actionable mutations who are treated with TKIs [tyrosine kinase inhibitors] who I will then see and treat for oligoprogression—a site, for example, that will grow—so we can keep the patient on that TKI a little bit longer. It’s most important for systemic therapy, but from the standpoint of a local modality like radiation, the better the systemic therapies, the more important local therapy becomes.

Philippa Cheetham, MD: You’ve talked, both of you, about mutational testing for systemic disease. But should we not be offering this to all patients for all disease? Surely, some of the treatments that are coming out apply these mutational markers. Is it not best to know that for everybody with lung cancer?

Leora Horn, MD, MSc: Are you talking about for patients with early-stage disease as well?

Philippa Cheetham, MD: Right.

Leora Horn, MD, MSc: Right now, for patients with early-stage disease, cure is generally achieved with surgery and chemotherapy. The reality is that if a patient progresses, you shouldn’t treat progression based on a CT scan. They need a new biopsy. You need that second biopsy if you’re suspicious that the cancer is back to confirm the cancer is back, because, as you know, things can mimic cancer. We never treat off just a scan. So, at the time they get that new biopsy, we’re going to do the molecular testing.

Philippa Cheetham, MD: Do you ever have a situation where a patient may present with what appears to be a good prognosis, localized disease, but they have surgery and then come back to you with recurrence? Do you think that for those patients, if you had mutational data up front, that may indicate this is more aggressive than previously thought and at a higher risk for recurrence? Would that not give you notice earlier in the game to think about treatments for patients who may be at high risk for relapse before we see anything on scans?

Leora Horn, MD, MSc: Right now, the biggest issue with that—that can happen—is some of those mutations are what we would call “not actionable.” For example, if a patient with early-stage disease has a KRAS mutation, we know that’s a poor prognostic indicator, but it’s not an actionable mutation. There’s no targeted therapy out there for KRAS-positive lung cancer. And so, having that information doesn’t necessarily mean we can help those patients with earlier stage disease to increase their chance of cure.

Philippa Cheetham, MD: Tell us a bit about the role now of these PD [programmed death] ligand medications for managing lung cancer. They’re being used not just in lung cancer, but also in many other cancers. They’re targeting the immune system. Are these medications the way forward? Are these better tolerated than chemotherapy, or is it just that they’re better at controlling the cancer in the first place?

Evan C. Osmundson, MD, PhD: I think that there’s a defined subset of patients with advanced disease who can be treated with these and can benefit from these. The PD-1 and PD-L1 pathway is just, in my opinion, the tip of the iceberg in terms of what is on the horizon for immunotherapy. The big picture concept is harnessing the body’s immune system to help fight the cancer. But, in terms of what these drugs actually do, they help the immune system recognize the tumor and help the patient’s immune system fight the tumor.

Transcript Edited for Clarity 
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