ALK Gene Rearrangements As A Therapeutic Target in Non-small Cell Lung Cancer - Episode 7

Brain Metastasis in ALK+ NSCLC

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Jyoti Patel, MD, and Karen Reckamp, MD, evaluate the treatment of patients with ALK+ advanced NSCLC with brain metastases.

Karen Reckamp, MD: Moving forward with CNS [central nervous system] activity, we’ve talked a lot about how we want to avoid radiation in these patients, and we want to talk about the data of why we can avoid radiation. As far as CNS metastases, you had mentioned that somewhere around one-third to a quarter of patients will have frontline metastases. Can you speak about the efficacy of the TKIs [tyrosine kinase inhibitors], listing them somewhat specifically, but more general categories? I know you did mention earlier that we can’t compare the efficacy, no cross-trial comparisons can be done, but talk about the efficacy of the TKIs in the brain.

Jyoti Patel, MD: Sure. We generally avoid crizotinib in patients who have CNS metastases, but if you look at the earliest trials, even crizotinib can have efficacy in the brain of about 40%. When we look at particular TKIs, brigatinib has had the most robust story with about a 79% CNS response rate, and alectinib is just under that in the mid-70% range. Again, these are drugs that are effective.

Karen Reckamp, MD: The response rate for lorlatinib was 82% versus 23% for crizotinib.

Jyoti Patel, MD: Right, and 79% for brigatinib. Again, the volume and number of lesions would matter as you’re making these decisions.

Certainly, there are a number of early trials or investigator-initiated trials that have tried to couple these TKIs with VEGF inhibitors—ramucirumab and bevacizumab—to try to increase CNS efficacy, though when it’s that high, it’s hard to do. So it is more looking at CNS relapse rather than true response rate up front, and lorlatinib, with that deep hazard ratio, sort of wins there.

Karen Reckamp, MD: With these drugs and the high response rates in the brain, what do we do for patients who do develop progression in the brain?

Jyoti Patel, MD: For new brain metastasis on lorlatinib, I would likely try, if I didn’t have an available trial, to add bevacizumab, if SRS [stereotactic radiosurgery] or limited resection were not feasible. Importantly, pemetrexed also has CNS penetration and chemotherapy does. If that’s the main site of progression and I didn’t have other local therapies available, then I’d switch to carboplatin and pemetrexed with or without bevacizumab.

Karen Reckamp, MD: It certainly is a challenge.

Transcript edited for clarity.