Target on cells

From IASLC Newsletter, September, 2016

Q&A with Alice T. Shaw, MD, PhD, and Ranee Mehra, MD

Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that was recently approved in the US as a second-line treatment for ALK-rearranged non-small cell lung cancer (NSCLC) after progression on the standard firstline therapeutic, crizotinib. Data from the J-ALEX trial,1 a Japanese phase 3 study directly comparing first-line efficacy and the safety of alectinib versus crizotinib, were presented at the 2016 ASCO Annual Meeting, showing that alectinib significantly increased progression-free survival (PFS) in patients.2 IASLC Lung Cancer News spoke with Alice T. Shaw, MD, PhD, from Harvard Medical School in Boston, Massachusetts, and Ranee Mehra, MD, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, to find out what these results might mean for the treatment of ALK-positive NSCLC.

Q: Is the J-ALEX study a “game changer” in terms of how we treat ALK-positive NSCLC?

Shaw: J-ALEX is almost a game changer. The results suggest that alectinib is superior to crizotinib as as first-line tyrosine kinase inhibitor (TKI) therapy, but there are some minor issues with this study that could impact extrapolation of the findings to all patients. Ultimately, we need to see the results from the global ALEX trial3 to confirm that PFS with alectinib is superior to crizotinib, and to determine the magnitude of the PFS benefit with alectinib.

Mehra: The hazard ratio (HR) of the alectinib arm versus the crizotinib arm reported at ASCO was 0.34,2 which is very impressive, so I think that J-ALEX is indeed a game changer.

Q: Should we adopt alectinib frontline routinely, even in the absence of the concomitant data from the global ALEX study?

Shaw: I think we should wait for the global ALEX results before we start using alectinib routinely as first-line therapy. I do think, however, that there are specific scenarios in which we should use firstline alectinib. Specifically, I believe alectinib can and should be used as a first-line therapy in patients who have ALK+ lung cancer and brain metastases at diagnosis, given the results from the single-arm phase 2 studies of alectinib4,5 and what we now know from J-ALEX in terms of the benefit of alectinib over crizotinib in patients with brain metastases.
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