WCLC 2019: LIBRETTO-001 Trial Reveals Antitumor Activity of RET Inhibitor
Posted: Friday, September 20, 2019
Results from the phase III LIBRETTO-001 trial, presented at the International Association for the Study of Lung Cancer 2019 World Conference on Lung Cancer (WCLC) in Barcelona (Abstract PL02.08), demonstrated that the RET inhibitor selpercatinib (LOXO-292) exhibits antitumor activity and appears to be well tolerated among patients with RET fusion–positive non–small cell lung cancer (NSCLC). Previously granted a Breakthrough Therapy designation by the U.S. Food and Drug Administration, selpercatinib exhibited durable response and “robust intracranial activity,” according to Alexander Drilon, MD, of the Memorial Sloan Kettering Cancer Center, New York, and colleagues.
“This continues to confirm that RET fusions are clinically targetable alterations, placing them in the company of activating EGFR, ALK, [and] ROS1 alterations,” the authors observed. “We are encouraged by these data, as there is currently an unmet need to provide genomically tailored therapy to patients with RET fusion–positive NSCLCs.”
In this global study, the investigators enrolled 105 patients with advanced RET-altered solid tumors, including RET fusion–positive NSCLC. The patients received selpercatinib orally in 28-day cycles.
The authors observed an objective response rate of 68% among the primary patients analyzed; they also found that a patient’s response to treatment did not differ by fusion partner or the type or number of prior therapies (including chemotherapy, anti–PD-1/PD-L1 agents, and multikinase inhibitors with anti-RET activity). The investigators also reported an intracranial objective response rate of 91% for those patients with measurable brain metastases.
Among patients with treatment-naive RET fusion-positive NSCLC assessed for efficacy, the objective response rate was 85%. In an analysis of a safety data set that included 531 patients, more than 15% of patients reported experiencing treatment-related adverse events (dry mouth, diarrhea, hypertension, and increased liver enzyme levels).
Disclosure: The study authors’ disclosure information may be found at wclc2019.iaslc.org.
