Alectinib eclipses crizotinib for ALK positive lung cancer

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Published: 5 Jun 2017
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Dr Alice Shaw - Massachusetts General Hospital Cancer Center, Boston, USA

Dr Shaw speaks with ecancer at ASCO 2017 about results from the ALEX trial of alectinib, a next-generation ALK inhibitor, for patients with lung cancer containing ALK mutations.

She describes the significant benefits of alectinib over crizotinib, with progression free survival at 25.7 months compared to 10.4 months, fewer side effects and a reduced incidence of brain metastases.

Overall, Dr Shaw encourages the use of alectinib as the new standard of care, and for doctors to discuss its use with patients currently receiving crizotinib.

Watch Dr Shaw present these results at a press briefing session here.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

Today we presented the primary results of the ALEX study which is a global randomised phase III study comparing alectinib with crizotinib in newly diagnosed advanced ALK positive non-small cell lung cancer patients. This was a global study enrolling over 300 patients worldwide, all with untreated advanced ALK positive lung cancer. Patients with brain metastases were allowed to enrol. Patients were randomised one-to-one to receive either alectinib or crizotinib as their first line treatment. The primary endpoint of the study was progression free survival based on investigator review with several key secondary endpoints like progression free survival based on independent review and time to CNS progression.

The primary endpoint of ALEX was met and alectinib was shown to be significantly superior to crizotinib in terms of prolonging PFS. Based on investigator review the median PFS with alectinib was not reached, with crizotinib it was about 11 months and the hazard ratio was 0.47 favouring alectinib and the p-value was highly statistically significant. We saw similar results based on independent review. With independent review the median PFS was estimated to be 25.7 months with alectinib and, again, about 10-11 months with crizotinib. This really corresponds to more than a doubling in progression free survival with alectinib.

One of the key secondary endpoints that we looked at in the study was time to central nervous system, or CNS, progression. ALK positive patients do have a propensity to CNS metastases and particularly on crizotinib many, many patients will relapse in the central nervous system. One of the analyses we performed was to look at time to CNS progression in all patients who enrolled in the study and we found that treatment with alectinib significantly delayed time to CNS progression compared to crizotinib. Here the cause-specific hazard ratio was 0.16 corresponding to an 84% reduction in the risk of having CNS progression as the first event.

One of the other important endpoints to mention is safety, so the safety of alectinib versus crizotinib was examined in the study. Both drugs were reasonably well tolerated but overall there were fewer grade 3 to 5 adverse events with alectinib and also fewer adverse events requiring treatment discontinuation or dose reduction with alectinib.

So overall the ALEX study, based on the superior efficacy as well as more favourable tolerability with alectinib, supports alectinib as a new standard first line treatment for patients with advanced ALK positive lung cancer.

With all of that in mind is there any reason to not use alectinib if it’s a unit cost for production or the healthcare costs are providing this as a medication or any patients who would be better off on crizotinib, are currently receiving crizotinib and ought not switch?

It’s a complicated question. For any newly diagnosed ALK positive patients that the data certainly support using alectinib in this situation. It’s a more complicated situation if a patient is already on crizotinib there I think we have to take it on a case by case basis. Definitely if the patients are on crizotinib and they have known CNS disease those are patients who likely will derive a lot of benefit from alectinib which is much more brain penetrable. But if you have a patient who has been on crizotinib for many years, tolerating the drug well, I think you do have to discuss with the patient the results of this trial and whether or not it makes sense to switch these patients or not.