BACKGROUND: Receptor tyrosine kinases (RTKs) play key roles in tumorigenesis. The multi-RTK inhibitor dovitinib has demonstrated promising antitumor activity in multiple cancers.
PATIENTS AND METHODS: In this phase 2, open-label, single-arm study, patients with advanced malignancies with RTK-pathway genetic aberrations whose disease progressed on/following standard treatment received dovitinib (500 mg/day; 5-days-on/2-days-off). The primary endpoint was clinical benefit rate (CBR; complete response, partial response [PR], or stable disease [SD] for ≥ 16 weeks).
RESULTS: Of 80 patients enrolled, common tumors included gastrointestinal stromal tumors (GIST; 20.0%), colorectal cancer (CRC; 18.8%), and ovarian cancer (10.0%). Patients were heavily pretreated (median prior lines = 4; 67.5% had ≥ 3 prior lines). Genetic aberrations included
CONCLUSIONS: In this heterogeneous patient population, the safety profile was acceptable for dovitinib therapy. A subset of patients with RTK pathway-activated tumors experienced clinical benefit. However, the primary endpoint was not met, suggesting further refinement of predictive biomarkers is required.
Earle A. Chiles Research Institute
Taylor, Matthew H; Alva, Ajjai S; Larson, Timothy; Szpakowski, Sebastian; Purkaystha, Das; Amin, Alpesh; Karpiak, Linda; and Piha-Paul, Sarina A, "A mutation-specific, single-arm, phase 2 study of dovitinib in patients with advanced malignancies." (2020). Articles, Abstracts, and Reports. 3773.