The Evolution of ALK/ROS1-Targeted TKIs

Transcript:Tony Mok, MD: ALK-rearranged lung cancer was actually discovered only in 2007. Since then, in 2011, there was a discovery and confirmation that the drug crizotinib proved effective in the management of the patients with this translocation. So, ever since then, we have routinely been looking for patients with this specific ALK translocation. Now every patient with adenocarcinoma, after we do EGFR mutation testing, we also look into the ALK presence or absence. If present, the first-line treatment will be crizotinib.

The difference of being able to identify patients with ALK translocation is significant. Because we now have a small molecule targeted therapy, which is namely a tyrosine kinase inhibitor, with which we’re able to control the cancer growth rather significantly. The response rate typically is around 70%, meaning that 70 out of 100 patients who use the drug will have dramatic reduction of the tumor. Furthermore, we’ll be able to control the disease for a longer duration of time. We actually have this study called PROFILE 1014, which we published in New England Journal of Medicine back in 2014, that proved with the randomized phase III study for ALK-positive patient there is superiority in both the progression-free survival and the response rate comparing crizotinib to standard chemotherapy.

David Spigel, MD: So, one of the big breakthroughs in the care of patients with lung cancer has been the understanding that we need to test patients for the presence of certain alterations, such as ALK rearrangements, to pick the best therapies for them. We know these occur in about 4% to 6% of patients with lung cancer. The reason it’s so important to test is because we have such effective therapies to use for these patients.

The main therapy that has been around that has shown the most dramatic benefit has been crizotinib. Crizotinib is an oral tyrosine kinase inhibitor that inhibits the ALK rearrangement. It is an effective therapy that has been proven to be better than chemotherapy as your first choice of therapy. So, really the standard of care globally is to know the patient’s ALK status, to test for that, and then offer them an option such as crizotinib to effectively control the cancer to allow patients to achieve high response rates, what are called “durable response rates,” where not only are you shrinking the cancer, but you’re maintaining that control, that remission, for extended periods.

Now there are some patients who won’t benefit. It’s rare, but you’ll have some patients who never get that response, or they get the response and it’s short-lived. That’s very frustrating. Fortunately, it’s a minority of the patients we care for. The majority of patients will get real shrinkage in their cancer and sustained benefits for many months. And many physicians who’ve treated a lot of patients with ALK-rearranged lung cancer will tell you about the patients they have with drugs like crizotinib, where they’ve gotten good control for even years. And that is quite rewarding to never have to offer a patient chemotherapy and really maintain good control, not only in their body but in the brain as well. It has been a fantastic development, and it’s really a standard of care in how we manage patients with lung cancer.

Transcript Edited for Clarity