Evolution of Targeted Therapy in Advanced NSCLC


Benjamin P. Levy, MD: Hello, and thank you for joining us for this Targeted Oncology™ presentation titled, “Targeting KRAS Mutations in Advanced Non–Small Cell Lung Cancer.” In non–small cell lung cancer, the most frequent oncogenic driver or mutation is KRAS, and there are not currently any approved therapies targeting KRAS. Today, we’ll learn about some of the new agents that are coming about, and we’ll talk about the recent advances in KRAS-mutated non–small cell lung cancer with a focus on these new therapies. I’m Dr Benjamin Levy, an associate professor at Johns Hopkins School of Medicine and clinical director of the Medical Oncology Unit at the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital in Washington, DC. Joining me today is Dr David Gandara, professor of medicine and senior adviser to the director at the University of California Davis Comprehensive Cancer Center in Sacramento, California. David, thank you for joining me, it’s a pleasure that we’re able to do this together. Let’s begin.

David R. Gandara, MD: There’s been, of course, a tremendous change in how we diagnose and reach treatment decisions in patients with stage IV non–small cell lung cancer. Maybe more than in any other type of cancer, biology has led the way in non–small cell lung cancer. Can you comment on how this has led to improved outcomes in patients? For example, let’s start with targeted therapies.

Benjamin P. Levy, MD: I think you stated it well. Lung cancer has been on the leading edge and has been the poster child for precision medicine. I got into this field just 12 years ago, and that was at the point where EGFR was being discovered as a relevant actionable mutation in non–small cell lung cancer with the IPASS trial data. We’ve come such a long way in the past decade or 15 years, with a better understanding of genetic alterations that define distinct molecular subsets. Of course, ALK came along several years later, and then the list continued to grow since then with RAS rearrangements, MET exon 14 skipping mutations, RET rearrangements, HER2, and all these other alterations that importantly define these molecular subsets that we can now wed to targeted therapies that are selective against particular protein products of the mutation.

As you’re aware, and you’ve led some of these studies, David, we’ve improved outcomes with these targeted therapies when we give the right drug to the right patient. My running joke is that I went into lung cancer because it was easy, and it is becoming extraordinarily complex. There’s always been a great degree of complexity with treating any tumor type. But we’ve come a long way in defining these distinct molecular subsets and developing targeted therapies that have certainly improved outcomes and improved, importantly—probably underrepresented in the literature—quality of life. Some drugs also do a great job crossing the blood-brain barrier. It’s an exciting time to be in the field of lung cancer.

David R. Gandara, MD: Thank you, Ben. It’s interesting, I haven’t heard you say this before, that you went into lung cancer because it was easy. I went into lung cancer because it was difficult. I looked at this as a challenge. I will say during the presidential address at ASCO [the American Society of Clinical Oncology annual meeting], when George Sledge, MD, showed the TCGA [The Cancer Genome Atlas] data on mutation rate, he compared all the different cancers. He said, “Down here with low mutation rates we have pediatric cancers and hematologic malignancies; no wonder they’re so easy to treat.” He said, “Over here at the far end, you see melanoma and non–small cell lung cancer…. These are the smart cancers.”

Benjamin P. Levy, MD: True.

David R. Gandara, MD: I think the fact that we’ve made advances is even more impressive because this is a smart cancer.

Benjamin P. Levy, MD: Yes, indeed.

Transcript edited for clarity.

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