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Insights From the ESMO Congress 2019: Immunotherapies in Lung Cancer |
Practice Community
Nashville, Tennessee
Practice Niche
Lung Cancer
Hospital and Institutional Affiliations
Chief Scientific Officer; Director, Lung Cancer Research Program
Sarah Cannon Research Institute
This interview has been edited for length and clarity, and was updated on 10/30/19.
Question What are some of the most encouraging new targets in lung cancer? |
Answer I wish we had some new targets, but in the last year or so I think we’ve been so focused on making sure we’re addressing kind of the main targets, which include the oncogenic drivers such as EGFR, ALK, and ROS. |
Question In your view, is immunotherapy-induced hyperprogressive disease a real phenomenon? If so, do you think testing for serologic biomarkers would be necessary before the administration of immunotherapies? |
Answer This concept of hyperprogressive disease is a bit controversial. Ultimately the premise is that patients responding to immune therapy we may lose that response and progress at a faster rate than if had they not been exposed to immune therapy. There’s a bit of a debate about this. There’s the perspective that there is no such thing as hyperprogressive disease, this is simply lung cancer that is progressing after another line of therapy.
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Question Should tumor-tissue assays and circulating cell-free DNA assays always be coupled, for an orthogonal approach in the detection of oncologic driver mutations in lung cancer? Why or why not? |
Answer It is important to search for potential oncogenic driving mutations to help decide what care patients should receive in the first-line setting. So upfront testing is essential. How you do that I think depends on your institution and the speed of turnaround time and of course, accessibility. Traditionally, tissue has been the best way to comprehensively profile patients, but it also is the way that takes the longest. Blood-based testing is emerging as a quicker way, and perhaps efficient or comprehensive way, to at least identify the most relevant markers upfront. |
Question Research suggested that surgery may influence the immunologic status of a patient. If true, how would this affect the use of immune checkpoint inhibitors in the neoadjuvant vs the adjuvant setting for early-stage NSCLC? |
Answer Yes, I think that’s a really exciting area. I think right now we don’t know enough about what surgery does to affect local immunity and if it’s a transient phenomenon. This has been described for I think over 2 decades now. There was some literature in this area in breast cancer originally that [reported that] breast cancer surgery creates a local cytokine storm that [generates] more protumor growth factors. Now we’re studying immunotherapy preoperatively and how to improve outcomes at and following surgery.
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Question What are some limitations of emerging “chemotherapy-sparing options,” if any? |
Answer I think in lung cancer, there is this drive to get away from chemotherapy. We certainly have examples in non-small cell lung cancer, where first-line therapy in many patients now could be just immunotherapy alone without chemotherapy. And I think there are potential limitations. Chemotherapy has had a role for decades in the treatment of cancers — specifically in lung cancer. If I use lung cancer as an example, in some of the comparative studies of immunotherapy vs chemotherapy or even chemoimmuno[therapy] versus chemo, there has been a suggestion of a crossover effect early on in the first 2 to 3 months, in which the chemotherapy-alone arm seemed to outperform immunotherapy, suggesting that you might need chemotherapy to bridge you through the first several weeks. |
Question Are there biological differences in immune landscapes across patients of other ethnicities that could skew findings that are thought to be applicable to people of all backgrounds? |
Answer Well, that’s a great question. I mean, I think the simple answer is: we don’t know. I think our literature is full of examples of how ethnicity can play a role in how patients respond to therapies — not just talking about things like disparities and access, and population-based differences in screening. I think if you’re talking about interventional studies, we’ve known historically for chemotherapy, ethnicity plays a role in how patients respond both in terms of efficacy and toxicity. And could this be true too with immunotherapy? I think it could be, but I don’t think we’ve seen any examples of this yet. Unfortunately, for most of the pivotal registration trials, there’s not been much variation. The ethnic variation has been limited and the population sizes within studies have been too small to notice differences. |