Trying to add immunotherapy regimens is another area of challenge. There have been such significant responses [with immunotherapy] in the rest of patients with NSCLC, but we do not see the same response of oncogenic-driven disease. We need to activate or inflame the immunotherapy environment in ALK
-positive disease so that it is responsive to immunotherapy.
What are some next steps researchers can begin taking for ALK-positive patients?
This is an exciting time for patients with ALK
-rearranged NSCLC and for those who treat patients with ALK
-positive disease. There have been tremendous strides. The biggest thing to keep in mind as we look at the current state of ALK therapy is that the first-line landscape has changed based on the ALEX and J-ALEX studies. These trials put alectinib as the standard of care for first-line therapy.
We have to consider what happens after alectinib-resistance, since much of the data being generated is for crizotinib resistance. For example, the FDA labels are for crizotinib resistance in the second-line setting. We need to further study what happens after resistance to second-generation TKIs and other treatment modalities or [develop more] rational combinations to [create] more durable responses.
Something that may be helpful is to target the persister cells that may be a source for future clinical progression or mutations. Local consolidative radiation is a particular modality that might be useful in that regard.
Solomon BJ, Shaw A, Ignatius Ou S-H, et al. Phase 2 study of lorlatinib in patients with advanced ALK+/ROS1+ non-small-cell lung cancer. In: Proceedings from the IASLC 18th World Conference on Lung Cancer; October 15-18, 2017; Yokohama, Japan. Abstract 8573.