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

Background

Cabozantinib monotherapy is approved for the treatment of several types of solid tumors. Investigation into the use of cabozantinib combined with other therapies is increasing. To understand the evidence in this area, we performed a systematic review of cabozantinib combination therapy for the treatment of solid tumors in adults.

Methods

This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and the protocol was registered with PROSPERO (CRD42020144680). On 9 October 2020, we searched for clinical trials and observational studies of cabozantinib as part of a combination therapy for solid tumors using Embase, MEDLINE, and Cochrane databases, and by screening relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Randomized and observational studies with a sample size of fewer than 25 and studies of cabozantinib monotherapy were excluded. For each study, quality was assessed using National Institute for Health and Care Excellence methodology, and the study characteristics were described qualitatively. This study was funded by Ipsen.

Results

Of 2421 citations identified, 32 articles were included (6 with results from randomized studies, 24 with results from non-randomized phase I or II studies, and 2 with results from both). The most commonly studied tumor types were metastatic urothelial carcinoma/genitourinary tumors and castration-resistant prostate cancer (CRPC). Findings from randomized studies suggested that cabozantinib combined with other therapies may lead to better progression-free survival than some current standards of care in renal cell carcinoma, CRPC, and non-small-cell lung cancer. The most common adverse events were hypertension, diarrhea, and fatigue.

Conclusion

This review demonstrates the promising efficacy outcomes of cabozantinib combined with other therapies, and a safety profile similar to cabozantinib alone. However, the findings are limited by the fact that most of the identified studies were reported as congress abstracts only. More evidence from randomized trials is needed to explore cabozantinib as a combination therapy further.

Informations de copyright

© The Author(s), 2022.

Déclaration de conflit d'intérêts

Competing Interests: 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. ABA has no interests to declare. 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. SV reports personal fees and non-financial support from Bristol Myers Squibb, personal fees and non-financial support from Roche, personal fees from MSD, personal fees from AbbVie, non-financial support from OSE PHARMA, and non-financial support from Merck. CR-A has no interests to declare. LM is an employee of Ipsen. 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.