A mutation-specific, single-arm, phase 2 study of dovitinib in patients with advanced malignancies

Abstract

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-dayson/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 cKIT (28.8%), FGFR3 (15.0%), and RET (15.0%). The CBR was 13.8%; one PR (GIST) and 10 SD (adenoid cystic [n = 3]; ovarian [n = 3]; GIST [n = 2]; CRC [n = 1]; gastroesophageal junction [n = 1]). The most common treatment-related adverse events were fatigue, diarrhea, nausea, and vomiting. 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.

In Silico Approach to Molecular Profiling of the Transition from Ovarian Epithelial Cells to Low-Grade Serous Ovarian Tumors for Targeted Therapeutic Insights

“…A few studies examined the relationship between ovarian cancer and dovitinib, AZD4547, ENMD, and brivanib, which are some other FGFR inhibitors that could be potential treatment agents ( Table 4 ). More research needs to be done on efficiency [ 41 , 42 , 43 , 44 ].…”

Design, Synthesis, Antitumor, and Antiplasmodial Evaluation of New 7-Chloroquinoline–Benzimidazole Hybrids

“…In recent years, benzimidazole compounds have gained even more attention due to their clinical application as anti-cancer therapeutics [35]. There are several examples of benzimidazole-based compounds that have been approved as anti-cancer therapeutics or have been a part of clinical trials, such as binimetinib, bendamustine, and dovitinib [36][37][38]. Due to their ability to interact with various therapeutic targets, benzimidazole compounds have also been investigated as antimalarials [39,40].…”