ASCO 2018 | ALEX: alectinib is the best first-line therapy available for ALK-positive NSCLC

The Phase III ALEX study, which was presented at ASCO 2017, compared the, at that point in time, standard first line ALK-inhibitor crizotinib with a next-generation ALK inhibitor, alectinib, in the treatment of naive ALK-positive advanced lung cancer. At that point in time the primary endpoint, which was investigator-assessed PFS, had a hazard ratio 0.47, but the median wasn’t reached. The independent radiology review committee had suggested that the median was going to be about 24-25 months, but at this ASCO we’ve seen an update on that investigator assessed primary endpoint, and now we do have a median, but it’s significantly higher. It’s 34.6 months and the hazard ratios have come down from 0.47 to 0.43. Now that’s gonna make people sit up and take notice. That’s a big jump in the apparent median, but one should recall that this is a very flat part of the curve; a few patients here or there can have a big jump in the median, and also this is investigator assessed. Now that was the primary endpoint of the study and going forward that’s the only updates we’ll get, and we all know that we all love our children and investigators tend to be more optimistic than an independent radiology review committee, but it’s still very encouraging and I think completely solidifies alectinib as the current best first-line standard for ALK-positive lung cancer.

I think there are a number of other drugs which in the post crizotinib setting have shown interesting activity: brigatinib, ensartinib and lorlatinib all have comparable first-line phase 3 studies reading out compared to crizotinib. Now we can see that they don’t all appear to be equivalent in that post crizotinib setting but whether that difference is going to translate to differences in the first-line setting we just have to wait and see.