A mutation-specific, single-arm, phase 2 study of dovitinib in patients with advanced malignancies
| Autor: | Linda Karpiak, Matthew H. Taylor, Sebastian Szpakowski, Alpesh Amin, Sarina Anne Piha-Paul, Das Purkaystha, Ajjai Alva, Timothy Larson |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Colorectal cancer histology-agnostic Phases of clinical research Knight Cancer Institute mutation-specific 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Clinical endpoint Hematology GiST business.industry Standard treatment Cancer medicine.disease advanced malignancies 030104 developmental biology 030220 oncology & carcinogenesis basket trial dovitinib business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Matthew H. Taylor 1 , Ajjai S. Alva 2 , Timothy Larson 3 , Sebastian Szpakowski 4 , Das Purkaystha 5 , Alpesh Amin 5 , Linda Karpiak 5 and Sarina A. Piha-Paul 6 1 Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA 2 Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA 3 USOR – Minnesota Oncology, Minneapolis, MN, USA 4 Novartis Institutes for Biomedical Research, Cambridge, MA, USA 5 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA 6 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Matthew H. Taylor, email: taylmatt@ohsu.edu Keywords: advanced malignancies; basket trial; dovitinib; histology-agnostic; mutation-specific Received: November 11, 2019 Accepted: March 03, 2020 Published: April 07, 2020 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-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 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. |
| Databáze: | OpenAIRE |
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