Patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) with BRAF V600E and/or K601E mutation status: A real-world view of effectiveness of lenvatinib monotherapy.

Francis P. Worden University of Michigan Health System Comprehensive Cancer Center, Ann Arbor, MI info_outline Francis P. Worden, Lori J. Wirth, Neil Reynolds, Charley Cooper, Olivera Rajkovic-Hooley, Gary Milligan, Phananh Pham, Hakim Saal, Marcia S. Brose

Authors Francis P. Worden University of Michigan Health System Comprehensive Cancer Center, Ann Arbor, MI info_outline Francis P. Worden, Lori J. Wirth, Neil Reynolds, Charley Cooper, Olivera Rajkovic-Hooley, Gary Milligan, Phananh Pham, Hakim Saal, Marcia S. Brose Organizations University of Michigan Health System Comprehensive Cancer Center, Ann Arbor, MI, Center for Head and Neck Cancers, Massachusetts General Hospital, Boston, MA, Adelphi Real World, Bollington, United Kingdom, Eisai, Los Angeles, CA, Eisai Inc., Nutley, NJ, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA Abstract Disclosures Research Funding Eisai Inc., Nutley, NJ, USA. Medical writing support was provided by Adelphi Real World, Bollington, Cheshire and was funded by Eisai Inc., Nutley, NJ, USA. Background: Lenvatinib was approved for the treatment of patients RAI-R DTC in the United States (US) in 2015, and the treatment landscape has evolved with agents targeting specific driver mutations. We assessed real-world clinical effectiveness of first line therapy with lenvatinib in patients with BRAF-mutated tumors, wild-type (WT) tumors, and patients who have not been tested for BRAF mutations (BRAF untested tumors). Methods: A retrospective chart review of RAI-R DTC patients in the US who initiated first-line lenvatinib monotherapy between February 13, 2015, and September 30, 2020. Data, including a boosted cohort of patients with BRAF-mutated tumors collected in late 2023, were abstracted from patients’ electronic health records and were de-identified. Descriptive analyses were conducted in patient cohorts with BRAF V600E and/or K601E mutated tumors, wild-type (WT) tumors, and BRAF untested tumors. Best response in first-line therapy was captured, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were assessed using Kaplan-Meier methods. Results: Of the 361 patients reviewed, 185 had records showing BRAF mutational status testing. 89 had BRAF V600E and/or K601E mutated tumors, 96 had WT tumors. 176 patients did not have BRAF mutational assessment. Of all subjects, 73.7% were White/Caucasian, 15.2% were African American, and 16.8% were Hispanic/Latino; 27.1% had ECOG performance status ≥2. The median follow-up times for each cohort were 30.0, 18.7 and 18.0 months, showing the longer follow up period for the BRAF-mutated cohort boost. Kaplan-Meier estimation for lenvatinib treatment discontinuation for the three cohorts at 24-months were as shown in the table below. Provider-reported overall response rate (complete or partial response) was 76.4%, 75.0% and 69.3% respectively. The estimated 24-month rwPFS rates (95% CI) were 74.1% (62.2%-82.8%), 61.7% (49.6%-71.8%), and 69.8% (60.9%-77.0%) respectively. Median rwOS was not reached for patients with BRAF-mutated and WT tumors, median OS was 54.2 months for BRAF untested tumors. Estimated rwOS rates at 12- and 48-months were 93.2% (85.4%-96.9%) and 83.9% (73.3%-90.3%) in BRAF-mutated patients, 90.6% (82.8%-95.0%) and 68.5% (53.4%-79.6%) in WT patients, and 90.2% (84.7%-93.8%) and 72.5% (61.6%-80.7%) in BRAF untested patients respectively. Conclusions: In this US real-world experience, the effectiveness of lenvatinib is consistent across a diverse cohort of RAI-R DTC patients with BRAF-mutated, WT, and BRAF untested tumors. This has implications for the first-line use of lenvatinib in BRAF mutated patients. Kaplan Meier estimations of time to discontinuation for lenvatinib first line. BRAF mut BRAFw t BRAF untested 24-months 67.5% (55.6%-76.9%) 60.0% (48.3%-69.9%) 65.3% (56.8%-72.5%)