A 61-Year-Old Man With ALK-Rearranged NSCLC - Episode 4
Mohammad Jahanzeb, MD:This patient responded to alectinib, which you expect 70% to 80% of patients to do, but the duration of response, or the progression-free survival was much shorter than 34 months9 months. I think this patient did not do as well on alectinib.
Resistance to these drugs is what frustrates us all. Eventually resistance develops, and we are trying to keep these patients from getting new chemotherapy by changing drugs. But it’s not a simple story likeEGFR, where 50% to 60% of patients that haveT790Mmutation. We have a drug, osimertinib, approved for that, and osimertinib is first line. Here there’s a whole potpourri ofALKalterations. It’s not just 1 major mutation. There are lots of mutations. And besides those mutations, there are other mechanisms of resistance, of amplifications, or bypass pathway activation, etc.
I think it’s imperative to do a biopsy or at least a liquid biopsya blood test—to see what type of resistance mechanism has emerged. There are different mechanisms. When you see a patient progressing on crizotinib, that’s a different spectrum from if the patient progresses on a second-generation ALK inhibitor. And 1 of the problematic mutations after progression on second-line therapy can be a 1202R mutation, which is covered by brigatinib at the dose of 180 mg. It is also covered by lorlatinib, the fifth approval that we got in subsequent-line therapy. But it’s not covered for alectinib, for example. So one has to be cognizant of what mutation it is, which drugs cover it, and which drugs don’t.
In terms of what we recommend after progression: biopsy, or at least a liquid biopsy. And if that’s negative, do not assume that there is no nonmechanism. Then go to a tissue biopsy in every case if possible.
Transcript edited for clarity.
Case: A 61-Year-Old Man WithALK-Rearranged NSCLC