A few years ago I found that we had ASCO, and then everything else. But over the last few years, it has become apparent that all the other major oncology conferences have emerged to compete to be front and center. It used to be that we waited for June in Chicago for breakthroughs, but now we have AACR, ASCO GI and GU, San Antonio Breast, the WCLC, ASH, of course, and many smaller niche conferences as a way of disseminating practice-changing data. The upside is there is more rapid and frequent dissemination of data; the downside is our attention has to be devoted year-round, and, in pre-COVID, it also meant lots of traveling. At least now we can Zoom in across the world.
With that in mind, there were a few hot topics this year as I see it. Kras G12C inhibitors made the headlines and Presidential Talk. Sotorasib’s (formerly AMG510) updated lung data was presented with a response rate of 37% and a duration of response of 10 months. Adagrasib (MRTX849) is a competitor in this class of drug, just a few months behind. The fact that we even have a drug that can target the kras gene is monumental. We’ve known about it forever, yet have made no headway, until now. Critics argue that the response rate is not what we expect for a targeted therapy. Yes, that’s true, it’s no osimertinib or alectinib for kras, but the fact that we are talking about this is huge. We still aren’t sure if these drugs ultimately will be relegated to second line, or combined with chemotherapy or immunotherapy, in the front line setting, or perhaps in combination with other drugs (eg SHP2 inhibitors). Still lacking are drugs that target beyond the C — there’s a lot of patients with other kras mutations (G12D, V, and a lot of others) that we hope to find drugs for soon. It’s truly remarkable we have come this far.
The other areas of interest for me this year were the EGFR world. There is a subset of EGFR mutations called exon 20 insertions which, albeit rare, are resistant to known EGFR inhibitors. Amivantamab, a monoclonal, was developed as a drug to overcome resistance to standard EGFR inhibitors for “typical” EGFR mutations as a combined monoclonal antibody against EGFR and c-met. Because it binds EGFR at the cell surface, it was also studied in the rarer exon20 group as well, and turns out, has substantial activity (RR 40%, duration about 11 months). Mobocertinib (formerly TAK788) is a small molecule TKI specifically designed to bind and turn off exon20 mutated EGFR inside the cell; its response rates were slightly lower but offers the option as an orally available drug. The challenges with both these drugs are the wildtype EGFR toxicities: rash, diarrhea, mucositis. We don’t typically see these effects with osimertinib any more and have forgotten. Furthermore, there doesn’t appear to be CNS penetration. That being said, these are previously untargetable mutations that we likely will have an FDA approval for before we know it. To say that to these patients is huge, regardless of the side effects.
Lastly, Jill Feldman gave a heart wrenching reminder of why we do this. She’s a stage 4 Lung cancer patient and advocate. She reminded us that patients and patient advocates need to be available from the get go on designing studies to make sure we pick better quality of life measures, and design trials so real patients can enroll. None of the above works unless we keep our patients in mind.
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