A Case of Metastatic ALK-Rearranged Non-Small Cell Lung Cancer - Episode 2
Lyudmila A. Bazhenova, MD:There have been a lot of very wonderful discoveries for patients withALK-mutant lung cancer. Currently, we have 2 drugs that are FDA approved for patients with newly diagnosed stage 4 lung cancer. One drug, which we already discussed, is crizotinib. The second drug that currently holds approval is ceritinib. Ceritinib received its approval based on a study that’s called ASCEND-4. ASCEND-4 is very similar to PROFILE 1014, which we discussed. It also took patients with stage 4 lung cancer,ALKmutant, who were not treated and randomized the patients to a platinum-based doublet or, in this case, ceritinib. And very similar to what I discussed in PROFILE 1014, we saw improvement in response rates, improvement in progression-free survival, and improvement in quality of life.
Regarding the upcoming role of alectinib, at ASCO 2017 the global ALEX study was presented. Compared with what we covered, PROFILE 1014 and ASCEND-4, the global ALEX study took patients who wereALK-positive, untreated, and then compared 2 ALK inhibitors head-to-head. So, patients were randomized to alectinib, which is a second-generation ALK inhibitor, versus crizotinib, which is a first-generation ALK inhibitor. And results of the study were not at all unexpected. We know that alectinib, by that being a second-generation ALK inhibitor, is probably stronger than crizotinib. The study showed that there was an improvement in progression-free survival at 12 months. There were more patients who were receiving alectinib who weren’t progressing at 12 months compared to patients who were receiving crizotinib. The median progression-free survival has not been reached yet for that study, so we will need to wait for the results. But because at 12 months, alectinib resulted in longer progression-free survival, I think the median is likely to be longer as well.
We have data in first-line therapy for 3 ALK inhibitors: crizotinib, alectinib, and ceritinib. If one looks at NCCN guidelines, all 3 ALK inhibitors are appropriate to use for patients with newly diagnosed lung cancer. My personal choice is alectinib, based on the results of the ALEX study. There is a trial looking at brigatinib versus crizotinib, in the first-line setting, very similar to the ALEX study. It’s not going to be alectinib versus crizotinib, but brigatinib versus crizotinib. The trial name is ALTA-1L. The study has, I believe, finished their accrual, but we do not have any results yet. I’m not aware of any direct head-to-head comparison trials of ceritinib versus crizotinib.
We can’t really use any stratifications without having head-to-head data. Those ALK inhibitors differ. They differ by side effect profile. Ceritinib causes more stomach toxicity, more diarrhea, and more nausea. Alectinib causes more muscle cramps. Crizotinib can cause edema. So, I think we have to make our decision at this point based on imperfect data, based on a toxicity profile, and based on a patient’s preferences. There are some medications that are used twice a day, which are alectinib and ceritinib. We have not yet covered brigatinib, which is a once-a-day medication.
Transcript edited for clarity.
ALK-Rearranged NSCLC Progressing on Crizotinib