Incidence and risk of severe adverse events associated with trastuzumab emtansine (T-DM1) in the treatment of breast cancer: an up-to-date systematic review and meta-analysis of randomized controlled clinical trials

ABSTRACT

Objectives

We performed an up-to-date meta-analysis to quantify the overall incidence and risk of severe adverse events (AEs) associated with T-DM1 in patients with breast cancer.

Methods

Pubmed, Embase, and oncology conference proceedings were searched for relevant studies. Data were extracted to calculate the summary incidence rate and relative risk (RR) of grade ≥3 AEs.

Results

A total of 5,045 patients from 7 RCTs were included in the meta-analysis. The use of T-DM1 was associated with an increased risk of severe thrombocytopenia (RR 10.66, 95% CI 3.23–35.18, P < 0.001), anemia (RR 1.68, 95% CI 1.15–2.44, P = 0.007), elevated ALT (RR 2.67, 95% CI 1.60–4.47, P < 0.001), and AST (RR 3.76, 95% CI 1.45–9.78, P = 0.007). In addition, the use of T-DM1 can increase the risk of severe hypertension (RR 1.59, 95% CI 1.03–2.45, P = 0.037) and peripheral sensory neuropathy (RR 8.13, 95% CI 1.89–35.03, P = 0.005).

Conclusions

Treatment with T-DM1 increases the risk of severe hematologic toxicities, hepatotoxicity, hypertension, and peripheral sensory neuropathy in patients with breast cancer, while the overall incidence of these AEs is low.

KEYWORDS:

• T-DM1
• breast cancer
• safety
• adverse event
• high grade

Declaration of Interest

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.

Reviewer disclosures

A reviewer on this manuscript has disclosed receiving honoraria from Roche. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

JH Zhang and HY Shi conceived and designed the study. K Liu and YH Li assisted with search and collection of the data. X Zhang, L Su, and JH Li were involved in the analysis and interpretation of the data. K Liu and X Zhang drafted the manuscript. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of work.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2022.2121704

Additional information

Funding

This manuscript was funded by the Baoding Science and Technology Project (No.17zf192); the Government-funded clinical talent training project (No.361007).