Invited discussant of the eXalt3 trial, Christine M. Lovly, MD, PhD, Associate Professor of Oncology and Hematology, and Ingram Professor of Cancer Research, and Co-Leader of the Translational Research and Interventional Oncology Program at Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, suggested future directions for researchers in the ALK landscape. Although there are now multiple options for first-line therapy with ALK tyrosine kinase inhibitors, said Dr. Lovly, it’s important for researchers to continue to “move the needle” for their patients.
“Ensartinib showed promising efficacy in the first-line treatment for patients with advanced ALK-positive lung cancer. However, we must continue to improve our thinking about combination therapies in the first line that extend the duration of benefit and combination therapies in the second line and beyond that overcome resistance,” Dr. Lovly stated. Researchers should also consider incorporating dynamic monitoring of response to ALK tyrosine kinase inhibitor therapy in prospective trials using circulating tumor DNA to be more nimble in adjusting therapy and consider comutations, such as TP53, that can affect response to TKI therapy, she added.
Christine M. Lovly, MD, PhD
In addition, said Dr. Lovly, there may be alternative ways to target ALK, including allosteric inhibitors, proteolysis targeting chimeras, and even vaccines. Using ALK tyrosine kinase inhibitors in the adjuvant setting may also be an effective strategy, she proposed, with trials ongoing in this space.
Other Tumors With ALK Fusions
Finally, Dr. Lovly emphasized the importance of translating findings from ALK-positive lung cancer to other tumor types that harbor ALK rearrangements.
“There are numerous other cancers that have ALK fusions, including pediatric lymphomas and sarcomas,” Dr. Lovly concluded. “As a field, we need to inform treatment paradigms for those patients as well.”
DISCLOSURE: Dr. Lovly has served as a consultant to Pfizer, Novartis, AstraZeneca, Genoptix, Sequenom, Ariad, Takeda, Blueprints Medicine, Cepheid, Foundation Medicine, Eli Lilly/Loxo, Genentech, and Amgen and has received research grants from AstraZeneca, Novartis, and Xcovery.
