COMMENTARY

Lung Cancer Sessions Focus on Immunotherapy, Genomics

Mark G. Kris, MD

Disclosures

June 01, 2016

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Hello. This is Mark Kris from Memorial Sloan Kettering, continuing my discussion on abstracts that are going to be presented at the upcoming meeting of the American Society of Clinical Oncology (ASCO) in Chicago. This year we're going to get more information about agents targeting PD-1/PD-L1 and CTLA-4. We're going to see that these benefits are also found in patients with malignant mesothelioma, both for anti-CTLA-4[1] and anti-PD-L1[2] therapies.

To help us understand these data from the immunotherapy trials, we're perhaps looking not so much at medians as the way to best judge benefit and quality of the data, information, and impact of the treatments that are being presented. There is going to be a presentation[3] on a pooling analysis from trials submitted to the US Food and Drug Administration and a discussion of that method of looking at information; perhaps that will guide all of us to better interpret clinical trials where the "median is not the message." Perhaps looking at the tail of the curve and looking at milestone analyses will be more effective for that.

We are going to have a number of presentations in the poster discussion section for metastatic lung cancer about KRAS.[4,5] KRAS, as Jerry Seinfeld would say, is the "big matzo ball hanging out there." It is the most common mutation we find. It's clearly a driver, but we do not have an agent on the shelf that can effectively attack it other than our traditional chemotherapies or anti-PD-1 and PD-L1 agents. The presentations ( Abstract 9018 and Abstract 9019) are going to look at co-mutations and see if they can help us provide a clue. And we're going to have a discussion by a true expert in the field, Jeff Engelman, who knows as much about KRAS as anyone. He also comes with a strong clinical perspective, and that should be good.

We've had a lot of questions about using radiation, and we finally have some randomized data to help us make decisions. There will be papers from MD Anderson comparing more commonly available radiation approaches with protons in a randomized trial,[6] and also the use of focused radiation in patients with oligometastases.[7] I think there's a huge emphasis and push to use radiation for patients with oligometastases, and you're going to hear some randomized data that can shed some light on the decisions for that. Again, you're going to see this at the sessions.

We've come to see that more and more patients with good control systemically relapse in the brain even with our effective new agents ceritinib, alectinib, and osimertinib. When there is still progression in the brain, that is a significant problem. There are newer drugs being developed for this, and two abstracts are being presented: one with higher doses of osimertinib in the leptomeningeal disease setting,[8] and one on AZD3759,[9] a kinase inhibitor specifically designed for better penetration into the central nervous system.

Many of you in the real world of oncology know about the availability of blood tests looking for DNA to give us the molecular information we need to better treat our patents. Many of you, I believe, are already using available commercial assays to look for T790M to help you make decisions about using osimertinib, for example. There is going to be a presentation where patients had mutational analysis of blood, tissue, and urine, and some discussion about pros and cons of those different testing capabilities. Clearly, this is going to be a huge wave in care. I think it is already, and it's becoming more and more routine. There will be some discussion about that by Heather Wakelee from Stanford, a leader in the development of using self-read DNA analysis for patient care. This is a new area; we're not talking about circulating tumor cells anymore. We're able to find robust demonstrations of mutations in the blood. It's a very simple test and one that's going to be used more and more in making treatment decisions.

I encourage you to spend the time, if you're in Chicago, to come to the lung cancer sessions. If you're at home, get into the virtual meeting and look at the two oral sessions in thoracic malignancies in metastatic and nonmetastatic lung cancers and other thoracic cancers, two poster discussions, and a clinical science symposium—a lot to learn, and hopefully we can quickly translate this into better care for our people fighting lung cancers.

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