Relapsed ALK-Rearranged NSCLC - Episode 5
Robert C. Doebele, MD, PhD:Following progression on crizotinib and the identification of anALKL1196M mutation, this patient was initiated on brigatinib at a dosage of 90 mg per day for 1 week. The patient did well during that time, with no respiratory issues, and was dose escalated to 180 mg of brigatinib.
This patient achieved a partial response in both the lung lesions and in the CNS [central nervous system]. She experienced some fatigue but was able to maintain some exercise. Importantly, her response was still ongoing at 16 months.
In thinking about this particular patient with anALKL1196M resistance mutation, she really has several options. Ceritinib, brigatinib, and lorlatinib have all shown in vitro activity againstALKL1196M, and there are clinical data to support the use of those drugs against that particular mutation. And so, any of those would be a reasonable choice.
When thinking about treatment following crizotinib, brigatinib has the longest progression-free survivalapproximately 15 to 16 months—whereas ceritinib and alectinib after crizotinib only have progression-free survival rates in the range of about 6 to 8 months. And so I think brigatinib is a very reasonable choice here. This patient has brain metastases. Brigatinib is a very good option for a patient with progression in both the brain and the lungs and has a very long progression-free survival.
We know that brigatinib has good potency across a number ofALKresistance mutations, includingALKL1196M. We know that in the clinical setting, post crizotinib, it has very significant activity in terms of response rate and progression-free survival. Importantly, it also has CNS activity and long progression-free survival specifically related to CNS metastases. That’s now been backed up by multiple trials post crizotinib.
Alectinib and ceritinib both have activity against several crizotinib-resistance mutations. In this particular case, the patient had already received alectinib, so using alectinib again probably doesn’t make much sense. Ceritinib has activity againstALKL1196M, and some mutations that are specific to alectinib, likeALKI1171, so that might be a good option for particularALKmutations. But again, if we just look at the clinical data in terms of progression-free survival and intracranial activity, brigatinib really stands out compared with ceritinib and alectinib as treatment post crizotinib.
Transcript edited for clarity.
Case: A 53-Year-Old Woman WithALK-Rearranged NSCLC