A 61-Year-Old Man With ALK-Rearranged NSCLC - Episode 3
Mohammad Jahanzeb, MD:When we look at this case, he progressed rather rapidly in 9 months rather than the 34-month progression-free survival that you expect. So this patient is not going to have the same prognosis as somebody who had a prolonged response to alectinib. You know, in the stock market, you say that past performance is no guarantee for future results. In oncology, it’s actually a very good predictor of future results. Patients who do poorly on first-line therapy tend to continue to do poorly. Patients who respond very well to first-line therapy are more likely to respond to subsequent lines of therapy.
Otherwise, if you’re not talking about this particular patient,ALK-rearranged patients have the best prognosis with stage IV disease. Currently, their survival in the modern literature is now approaching or exceeding 5 years. We never thought we’d use the term5-year survivalfor stage IV lung cancer, but forALK-rearranged patients, we can now start thinking in those terms. I have patients who are now 7, 8 years out on ALK inhibitors with multiple lines of therapy.
When we look at emerging treatment options and go to the NCCN [National Comprehensive Cancer Network] Guidelines and open them for first-line treatment, there are 4 options listed. There’s crizotinib, which was the earliest. Then came ceritinib, then alectinib, and now brigatinib is the latest addition.
Now, one would think, why would you leave crizotinib in? That was defeated handily by alectinib10.4 months versus 34 months, with a huge delta. But one has to realize that the NCCN considers itself a global organization. There are countries that have only crizotinib available. If you exclude it from the guidelines, a payer can make that excuse and say, “It’s not even in the NCCN Guidelines. Why should we cover it?” That’s why the NCCN Guidelines are more like a 50-lane highway. They don’t depend on FDA approvals.
If something is already FDA approved and is on the market, and there’s evidence to support its inclusion, the panel can vote on it and put it in the guidelines. Because brigatinib was already approved for second-line use, they could make it available for the first line long before the FDA actually gets around to approving it.
The NCCN Guidelines have these evidence blocks where they weigh things by their efficacy, toxicity, cost, etc. That, in general, has not proven to be a very useful exercise. We really still have to rely on clinical trials data and information in the package insert. We do know that myalgias are a known adverse effect of alectinib.
This doesn’t really appear to be the case with brigatinib. Brigatinib has this uncommon 3%-to-5% type of early pulmonary toxicity that can be monitored and responded to, but it’s not the same pulmonary toxicity that we see with immunotherapy, which is immune pneumonitis, which needs prolonged steroid use and a slow taper. This is not that type of a pulmonary reaction.
So there are these differences. Plus, the other difference is alectinib is administered as 4 pills twice a day. Brigatinib is 1 pill given once a day. There’s that convenience factor that comes in. The data that were published in theNew England Journal of Medicinehave a shorter follow up. But at the 1-year mark, the data appear to be similar. I think if most follow-up of these data pan out, brigatinib may become the preferred option because of its CNS [central nervous system] penetrance, its convenience, and its slightly better toxicity profile.
Transcript edited for clarity.
Case: A 61-Year-Old Man WithALK-Rearranged NSCLC