Use of Immunotherapy Could Grow to All NSCLC Settings

Immunotherapy agents, though now only used in the second-line setting to treat non-small cell lung cancer (NSCLC), will eventually move up and be used for patients in all settings, says Edward Kim at the 3rd Annual Miami Lung Cancer Conference.

"We're hopeful that there will be multiple indications," says Kim. "I'm hopeful that there will be multiple combinations that will look promising and hopefully be approved. Of course, if we can find a biomarker-directed population, that would be ideal. That is my biggest wish list for 2017."

In an interview with CURE, Kim, chair of the Department of Solid Tumor Oncology, Levine Cancer Institute, discusses the FDA-approved immunotherapies Opdivo (nivolumab) and Keytruda (pembrolizumab) along with other potential combinations, biomarkers and ongoing research.

What are you most excited about in the space of immunotherapy in lung cancer?

The impact of immunotherapy in NSCLC has been tremendous. The uptake and interest by both providers and patients has been really unprecedented, especially because of the wide applicability of their use. We now have second-line therapies as a single agent with two different immunotherapies.

What we're hoping for in the next year is to see if there will be expanded indications, most notably in the frontline setting. There are multiple studies being done that are combining these immunotherapies with chemotherapy and with biologic therapy. Where all of the dust settles in the next year is going to be very interesting.

What does the future hold for immunotherapy biomarkers in lung cancer?

Frankly, I've never been a fan of expression markers. They can be helpful sometimes, but there is usually a gradient and, because you're picking a certain point on that gradient, you're going to see folks with some expression, and higher expression. I hope that whatever markers are indicated—if there are markers indicated—really show a distinct difference within populations. Maybe it will be a single marker, maybe it will be a combination of markers, and maybe it will be a panel that exists. There are a lot of people working on this question.

My hope is that it's not too complicated or cumbersome, because not only does that slow down getting the patient on therapy but it also confuses our payers in that standpoint. Equally important are the physicians and providers knowing the drug, patients being able to take the drug, identifying the appropriate patient, utilizing the appropriate marker, and making sure there is no delay in payment for that therapy.

Which combinations being tested right now are you most excited about?

There are many, many combinations. We have multiple studies open at Levine Cancer Institute. I'm probably more biased toward having non-cytotoxic regimens—in the spectrum of epidermal growth factor receptor mutations, it’s been fantastic for patients with those mutations. They can take a pill and then when the drug stops working and their tumor begins to grow, more than half of them will have the opportunity for another pill. The fact that we can say that patients with stage 4 lung cancer could take oral biologic therapy for years is amazing, especially in the context of where we were in 2000 or 2002.

I hope that the same thing happens for immuno-oncology—that we're able to identify strategies that have lower side effects that control the tumor just as well. Anything that we can do to displace more toxic therapies with less toxic, more tolerable therapies, I think is a win.

Do you see immunotherapy moving up in settings?

Currently we have approvals in second-line. Hopefully next there will be approvals in first-line, and then hopefully there will be first-line maintenance aspects, as well as the combinations of drugs in the first-line, whether they would be chemotherapies or otherwise. There will be a sequencing question, naturally, if you have first-line approvals and second-line approvals, can you give one first and another one second? Or vice versa?

There will naturally be questions of third-line treatments, as well, and maybe we will mimic the melanoma world where we are doing combination immuno-oncologic therapies. Maybe we will start looking at it in the locally advanced setting with radiotherapy as a maintenance therapy after definitive treatment.

Everyone dreams about moving to the post-resected, post-curative treatment era. However, as we know, based on a lot of studies that we've done, it's a very difficult space to find an impact. There is hope in this strategy of trying to utilize your own body's defenses makes people a lot more confident that these strategies may yield something more significant.

As more of these therapies become widely used, is there a learning curve for oncologists?

There is a little bit of trepidation whenever you use a new therapy. We're more conditioned to treat neutropenic fever and sepsis and neuropathy than we are with these endocrine abnormalities that occur, or these immune-related side effects. There is a learning curve but, I think what people can feel confident about is people like Jimmy Carter, who had metastatic melanoma and is being treated with an immunotherapy. He's in his 90s and is doing very well, so that's a good example of how tolerable these drugs are and how you can treat many different patients.

How do you choose which agent to use?

They are not equal in the fact of how they're indicated. One requires expression of a marker and another does not. Right now, many physicians will take the path of least resistance. I like having choices; the more the merrier. The better drugs should rise to the top, so I hope we have four or five choices in this space, and that the data is what will push us through.

Medicine is very complex and the practice of medicine is becoming more challenging these days. Providers are seeing more patients, they're getting less time to see these patients, and they're being paid less to see these patients. Any extra steps that are inserted in a clinical flow, a treatment flow, if there are any questions about reimbursement, these are resources that many practices just don't have the capacity to spend a lot of time with. Anything that is simpler, easier and equally effective, is going to be better.