A 61-Year-Old Man With ALK-Rearranged NSCLC - Episode 7
Mohammad Jahanzeb, MD:When we think of future directions forALK, 1 thing we keep in mind is that most community medical oncologists who are not focused on lung cancer will probably see fewer patients withALK-positive lung cancer, where there are already pills available in the market to treat. The experience is not going to be broad and vast. We constantly try to further the field to see what’s next and how to best sequence these drugs. Sequencing these drugs is going to be a huge issue. You have so many options, and patients will eventually become resistant to 1 or the other or the next.
There’s an NCI [National Cancer Institute]NRG [Oncology] ALK Master Protocol that actually relies on assessment of resistance mechanisms or rebiopsy and mutation testing. Patients are sent to the right pathway to pick the drug that does cover that mechanism of resistance. Since there’s overlap, there are multiple options at these decision points. So the trial gives us at least a repository of data with tissue available to analyze, which will expand our understanding of how to further develop these compounds or how to combine them. So combinations are another avenue. Unfortunately the data that we have point to immunotherapy being relatively useless. We have to find nonimmunotherapy partners and see how maybe they could be integrated in some fashion with chemotherapy drugs with other new emerging compounds. That’s going to be the direction we’ll go in the future.
When we think of immunotherapy, for cancers that have developed under carcinogenic pressurelike melanoma under ultraviolet radiation, or toxic substances and tobacco smoking, for which you’ve seen cancers of the head and neck, esophagus, lung, bladder, etc—we expect accumulations of a lot of mutations, a high tumor mutation burden, and a separate biomarker from PD-L1 [programmed death-ligand 1]. We tend to see immunotherapy as more effective. For cancers that are otherwise pristine but have 1 thing wrong with them, there’s 1 pathway. It’s likeEGFRorALK. They’re not immunogenically as distinct from the rest of the body. So immunotherapy tends to be less effective in those tumors.
Transcript edited for clarity.
Case: A 61-Year-Old Man WithALK-Rearranged NSCLC