Targeted therapy for solid tumors and risk of hypertension: a meta-analysis of 68077 patients from 93 phase III studies

ABSTRACT

Objective: Hypertension is a common adverse event with targeted agents in cancer patients and can lead to serious and sometimes lethal cardiovascular complications. The authors performed a meta-analysis of clinical trials aiming to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade Hypertension Events (HE) in patients with solid tumors receiving targeted therapy.

Methods: A review of citations from PubMed was performed and studies were selected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was limited to randomized phase III trials published in English focused on the efficacy and safety of targeted agents in cancer patients, reporting data on HE. Incidence, RR and relative 95% CIs were analyzed using random or fixed-effects models. Overall incidences were calculated and further compared with the chi-squared test for proportions.

Results: Ninety-three phase III trials were included, with a total of 68,077 patients. Prostate cancer was the most represented (18.9%), followed by breast cancer (17.3%) and colorectal cancer (16.4%). The incidence of all- and high-grade HE was 23.47% and 8.57%, respectively, with the highest incidence of serious HE reported by adjuvant Sunitib/Sorafenib (29.03%). The highest RR of high-grade HE was observed with Bevacizumab in patients with advanced cervical cancer. By drug category, the highest RR of high-grade HE was reported by VEGFR/EGFR TKIs.

Conclusion: According to these data, monitoring this class of toxicities is of primary importance to avoid hypertension worsening and, thus, the risk of major cardiovascular events.

KEYWORDS:

• Cancer
• Cardiovascular events
• Hypertension
• Meta-analysis
• Targeted therapy

Article highlights

• Among the adverse events (AEs) associated with targeted agents, hypertension is surely one of the most frequent. Cardiovascular events can dramatically affect the outcome and Quality of Life.

• The development of hypertension is mainly, but not only, due to the inhibition of Vascular Endothelial Growth Factor (VEGF) and its receptor (VEGFR).

• The aim of this study was to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade HE in patients with solid tumors receiving targeted therapy.

• This meta-analysis has confirmed how globally HE are particularly frequent in patients being treated with targeted agents, with a global incidence of 23.47% and 8.57% for high-grade events (RR 4.41 and 3.31, respectively).

• A multidisciplinary approach with cardiologists for the early beginning of an adequate antihypertensive therapy is recommended in patients undergoing targeted therapy.

• Some concomitant antihypertensive drugs may influence the survival of cancer patients treated with targeted therapies.

Acknowledgments

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Author contributions

• Conception and design: MS, AC, RM, NB

• Analysis and interpretation of the data: FM, VdN, LF, LC

• Drafting of the paper: EG, JM, FP, SB, ALB

• Revising the paper critically for intellectual content: RI, BF, AC, MS

• All the authors have approved the final version of the paper and have agreed to be accountable for all aspects of the work.

Declaration of interest

No potential conflict of interest was reported by the authors.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

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Additional information

Funding

This paper was not funded.