Oncotarget

Research Papers:

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

Matthew H. Taylor _, Ajjai S. Alva, Timothy Larson, Sebastian Szpakowski, Das Purkaystha, Alpesh Amin, Linda Karpiak and Sarina A. Piha-Paul

PDF  |  Full Text  |  Supplementary Files  |  How to cite  |  Press Release

Oncotarget. 2020; 11:1235-1243. https://doi.org/10.18632/oncotarget.27530

Metrics: PDF 1120 views  |   Full Text 1791 views  |   ?  


Abstract

Matthew H. Taylor1, Ajjai S. Alva2, Timothy Larson3, Sebastian Szpakowski4, Das Purkaystha5, Alpesh Amin5, Linda Karpiak5 and Sarina A. Piha-Paul6

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: [email protected]

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 27530