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Small Cell and Non-Small Cell Lung Cancer Updates

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Published on June 26, 2020

Small Cell and Non-Small Cell Lung Cancer Updates

Are there new treatment options for both small cell and non-small cell lung cancer patients? What about clinical trials for those whose lung cancer has transformed?

In this segment from our recent Lung Cancer Answers Now program, host Andrew Schorr gets updates from Dr. Heather Wakelee of Stanford University School of Medicine on new drug approvals that came out of the American Society of Clinical Oncology (ASCO) meeting. Watch as she explains options for patients with ALK mutations, new medications for small cell lung cancer patients and more.

This is Part 3 of a three-part Lung Cancer Answers Now program. Watch Part 1 here and Part 2 here.

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Transcript | Small Cell and Non-Small Cell Lung Cancer Updates

Andrew Schorr:
So Dr. Wakelee, let’s start to get into information about progress. Here’s a question that came in — and maybe you can tie this to news that’s happening, Dr. Wakelee. So this patient said, “Are there any upcoming clinical trials for those of us with non-small cell lung cancer with an EGFR 19, who were transformed to small cell lung cancer?” And that the options have been really limited. So, people worry about these transformations, I know you and colleagues are researching these very things, so update us on that.

And also, we had a big cancer convention, The American Society of Clinical Oncology, a couple weeks ago. Lung cancer was discussed a lot. Give us an update.

Dr. Wakelee:
What it speaks to is the fact that when we find tumors that have these specific mutations in them, in Linnea's case it's the ALK, we have a lot of great medications that can control it, but unfortunately, tumors change over time, and they become resistant. And there're different ways that can happen. Sometimes a different pathway gets involved, sometimes there's another mutation that develops, and sometimes the cancer really changes, go from non-small cell to small cell. And when we first learned about this phenomenon, I remember I was at the conference in Lecia Sequist presented the data, and we all had our jaws drop, because it didn't fit with how we understood cancer. But it's been confirmed that that is one of the things that can happen, is the cancer changes itself so drastically, it behaves differently. We traditionally treat that with chemotherapy when that happens, but there is work being done.

And we're actually within the cooperative group, ECOG ACRIN, Lecia Sequist, is leading an effort to develop a trial, to ask the questions. Should we treat patients who, where this happens, we know we need to give them small cell chemo, but what's happening for treating small cell in general is chemotherapy plus immune therapy. And we don't know if that's the same plan that would be best in small cell, or should we keep going with the EGFR medication for whatever non-small cell cells are still there that are still dependent on EGFR, and then add the chemo to that? So we're working on trying to understand that. And it's a great question.

Andrew Schorr:
Let me pop another one on you, just because it may tie in. This came in, too. So here's somebody wondering about new therapies for what Linnea's dealing with, ALK-positive stage four, non-small cell lung cancer, and they had heard something about cell therapy or new immunotherapies, or even combining that. So maybe that's been discussed, as well.

 Dr. Wakelee:
Great. So with ALK, and Linnea was discussing her amazing story - I was just really thrilled to meet you- about how she was one of the first people on crizotinib (Xalkori), which was the very first ALK drug. And it was right as people were understanding ALK, this drug was available that actually hits other targets also, but hit ALK, and that became our first ALK drug. But, it wasn't designed just to hit ALK. And so newer drugs have been developed that are more specific to ALK, and we actually have five that are FDA approved, which is amazing, and trying to understand how we can sequence. But just as I mentioned in an EGFR, eventually the best targeted drugs we have, stopped working for most, but not all people. And with ALK, the same thing can happen, different resistance pathways can develop. And so there's a lot of work on trying to understand, well when the ALK drug stops, why? Sometimes it's a new mutation in which case, one of the other drugs that are ALK-focused might work.

Sometimes it's a different pathway. In which case, we can combine things together. The bigger part of that question is about immune therapy, and that's where there's some challenges. When I talk to a patient about lung cancer, I talk about for metastatic disease, that there are three main categories there's chemotherapy, and that plays an important role for most people with advanced cancer, just not always right at the beginning, depending on other aspects of their tumor.

There are targeted therapies, which are medications that we can use when the cancer has a specific mutation. And so, that either is there or not, it's just what developed the cancer. So some patients have it, and some people don't, and it's really, really important to do the testing, to figure out whether or not a patient's tumor has that mutation. If we don't test, we don't know. And if we don't know, we can't treat, in that situation, as well as we could.

And then there's immune therapy. And the immune therapy drugs, there're now five of them approved for just for lung cancer. These are what we call checkpoint inhibitors or immune therapy, PD-1 PDL-1 drugs. They have a lot of names, and those work very, very well when there's a high level of PDL-1 or high tumor mutation burden. There was just an approval for one of them this week. Or sometimes, we don't know why they're working, it's not as straightforward as with the targeted therapies. But they can be given alone or in combination with chemotherapy and work very well for some patients.

What's interesting is that usually the people whose tumor has the driver mutations and get targeted therapy, often don't respond as well to the immune therapy. So you end up with better treatments for different people. When do we bring those together? How can we best treat people who have the targeted mutations with immune therapy? And there is a lot of research being done there. Giving just these checkpoint inhibitors alone, is for many people with the driver mutation, not the best, but combining it with chemo could be. And I think this question was more about the next wave of immune therapy, which isn't just these synched drugs that are a little bit nonspecific, but really trying to specifically target the tumor. And there are a lot of newer things in development for that. I'm not aware of any that are specific to ALK, and a lot of these early ventures into the modified T-cells, these CAR-T's, all that, it's a little slower in the solid tumors, but there's a lot of progress being made.

Andrew Schorr:
Dr. Wakelee, we have a subset of people with lung cancer, with small-cell cancer, not necessarily to transform, but they have small-cell. And things were really tough for them. There've been so many approvals, but not so much in small-cell. Any news there you want to share with people?

Dr. Wakelee:
So yes, a couple of exciting things. So first of all, this idea that we should be giving chemotherapy plus immune checkpoint inhibitors, that was something that we were hopeful about, and now we've had four trials showing that with approvals for both atezolizumab (Tecentriq) and Durvalumab (Imfinzi), so that's really exciting. And then, just last week, the week's all blur together now, but there was an approval of a second-line treatment, so for people who have progressed, and that's Lurbinectedin. And so that was pretty exciting to have a new drug in small-cell, also just approved. So there is hope, and there is a lot of research being done there. And that's an area where the immune therapies are really being explored as well.

Andrew Schorr:
Well, what I like to say is you all, and I’m including you Linnea, are our angels. Linnea, you’re an angel for being in trials, and helping pave the way for other people – not just yourself. Dr. Wakelee, leading research at Stanford, and your devotion to lung cancer patients. Amy, your whole background in basic science, and then helping bring that knowledge to the GO2 Foundation. You are angels and thank goodness there’s more to talk about. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.

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