Cabozantinib for the treatment of solid tumors: a systematic review.

Background: Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been investigated for the treatment of other cancers. With the available evidence and the real-world performance of cabozantinib compared with clinical trial data, we performed a systematic review of cabozantinib monotherapy as treatment for solid tumors in adults.
Methods: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42020144680). We searched for clinical and observational studies of cabozantinib monotherapy for solid tumors using Embase, MEDLINE, and Cochrane databases (October 2020), and screened relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Small studies ( n  < 25) and studies of cabozantinib combination therapies were excluded. Quality was assessed using National Institute for Health and Care Excellence methodology, and study characteristics were described qualitatively.
Results: Of 2888 citations, 114 were included (52 randomized studies, 29 observational studies, 32 nonrandomized phase I or II studies or pilot trials, and 1 analysis of data from a randomized study and a nonrandomized study). Beyond approved indications, other tumors studied were castration-resistant prostate cancer, urothelial carcinoma, Ewing sarcoma, osteosarcoma, uveal melanoma, non-small-cell lung cancer, Merkel cell carcinoma, glioblastoma, pheochromocytomas and paragangliomas, cholangiocarcinoma, gastrointestinal stromal tumor, colorectal cancer, salivary gland cancer, carcinoid and pancreatic neuroendocrine tumors, and breast, endometrial and ovarian cancers. The most common adverse events were hypertension, diarrhea, and fatigue.
Conclusion: The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types, with safety findings being consistent with those observed with other VEGFR-targeting tyrosine kinase inhibitors. When available, real-world findings were consistent with the data reported from clinical trials. A limitation of this review is the high proportion of abstracts; however, this allowed us to capture the most up-to-date findings.
Competing Interests: Conflict of interest statement: PM is on advisory boards for Astellas, AstraZeneca, Bayer, Bristol, Ipsen, Janssen, Novartis, Pfizer, and Roche, and has received research grants from Bayer and Roche. CP has an advisory role with AstraZeneca, Bristol Myers Squibb, Eisai, EUSA Pharma, General Electric Healthcare, Ipsen, Janssen, MSD, Novartis and Pfizer; has been a speaker for Bristol Myers Squibb, EUSA Pharma, General Electric Healthcare, Ipsen, and Pfizer; has been a protocol steering committee member for Bristol Myers Squibb, Eisai and EUSA Pharma; and has provided expert testimony for EUSA Pharma and Pfizer. JC has a scientific consultancy role (speaker and advisory roles) for Advanced Accelerator Applications, Amgen, Bayer, Eisai, Exelixis, Ipsen, ITM, Merck Serono, Novartis, Pfizer, Sanofi and Sirlex, and has received research grants from Advanced Accelerator Applications, AstraZeneca, Bayer, Eisai, Novartis, and Pfizer. ABA has no interests to declare. SV reports personal fees and nonfinancial support from Bristol Myers Squibb, personal fees and nonfinancial support from Roche, personal fees from MSD, personal fees from AbbVie, nonfinancial support from OSE PHARMA, and nonfinancial support from Merck. CR-A has no interests to declare. LM is an employee of Ipsen. DC has received institutional research funding from Janssen Oncology; has received travel and accommodation expenses from AstraZeneca (Spain), Bristol Myers Squibb, Pfizer and Roche; and has a consulting or advisory role with Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Ipsen, Janssen Oncology, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, and Sanofi.
(© The Author(s), 2022.)