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

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.

Déclaration de conflit d'intérêts

CONFLICTS OF INTEREST M.H. Taylor reports receiving honoraria for Advisory Boards from ArQule, Array Biopharma, Bayer, Blueprint Medicines, Loxo Oncology, Novartis and honoraria for Advisory Boards and Speakers fees from Bristol-Myers Squibb and Eisai, outside the submitted work. A.S. Alva reports grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis Oncology, Esanik, Genentech, Ionis, Janssen, Merck, Progenics, and Prometheus; and personal fees from Merck and AstraZeneca for Advisory Boards, outside the submitted work. T. Larson has nothing to disclose. S. Szpakowski reports employment by, and stock ownership of Novartis. D. Purkayastha, A. Amin, and L. Karpiak report employment by Novartis. S.A. Piha-Paul reports clinical trial research support from AbbVie, Aminex Therapeutics, BioMarin Pharmaceutical, Boehringer Ingelheim, Bristol-Myers Squib, Cerulean Pharma, Chugai Pharmaceutical, Curis, Five Prime Therapeutics, Genmab A/S, GlaxoSmithKline, Helix BioPharma, Incyte, Jacobio Pharmaceuticals, Medimmune, Medivation, Merck Sharp & Dohme, NewLink Genetics Corporation, Blue Link Pharmaceuticals, Novartis, Pieris Pharmaceuticals, Pfizer, Principia Biopharma, Puma Biotechnology, Rapt Therapeutics, Seattle Genetics, Taiho Oncology, Tesaro, TransThera Bio, and Xuan Zhu Biopharma, outside the submitted work.