ESMO 2020 | ALTA-1L updates at ESMO 2020: intracranial efficacy and HRQoL

At the EMSO meeting we also presented updated data from the second interim analysis of the ALTA-1L trial, and you’ll remember that this was a randomized phase three trial of Brigatinib versus Crizotinib in patients with locally advanced or metastatic ALK+ non-small cell lung cancer. Here, unlike the Crown and Alex studies, patients could have had chemotherapy as their first treatment, as long as they hadn’t progressed. This was done to keep the disease under control, whilst screening and then running into the studies. The updated data did confirm the significant efficacy of Brigatinib with a hazard ratio of 0.49 for progression-free survival by blinded independent radiology review, which is very comparable to what we’ve seen thus far in the Alex study with Alectinib.

Here, at the ESMO meeting, we presented updated intracranial efficacy data and looking at the progression-free survival in patients with CNS disease, we see a blinded independent review PFS hazard ratio of 0.25. This really demonstrates the marked efficacy of Brigatinib in patients with baseline CNS metastases, which accounts for about 25% of the study population.

Now this hazard ratio is far superior to what we’ve seen with Ensartinib and Alectinib in Alex to date. Although it’s very difficult to make cross trial comparisons, I would suggest it is relatively similar to what we also heard at the ESMO meeting for Lorlatinib with a hazard ratio of a 0.2 for patients with CNS metastasis. We also have more data about the brain efficacy. Brigatinib has the integral progression-free survival of 0.45. Now this is a good bench mark because we’ve not really seen that type of end point before and certainly we’ll all be looking for that end point for the Crown Lorlatinib data, because at the moment we’ve only seen time to intercranial progression, which is a slightly different end point.

And finally, we have some clearer data on the nature of CNS relapses in patients and the ALTA-1L demonstrating that Brigatinib did reduce the number of patients with the brain as the first site of progression compared to Crizotinib. I guess you would expect this given its intracranial activity and if you look at the pattern of progression in the brain, it tends to be new metastasis rather than established disease.

Also, at the meeting, we presented updated quality of life data from the ALTA-1L trial and clearly we see that there is an improvement in quality of life in many domains, but particularly in global health score, which is improved compared to Crizotinib. So I think taking account both the improvement in quality of life, the intracranial efficacy data, the established safety data associated with an improvement in quality of life and the overall efficacy data, Brigatinib is clearly a frontline treatment option for our first-line ALK+ patients.