Interstitial lung disease associated with anti-HER2 anti-body drug conjugates: results from clinical trials and the WHO's pharmacovigilance database

ABSTRACT

Background

Interstitial lung disease (ILD) events associated with anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) have aroused wide attention.

Research design and methods

In meta-analysis, we systematically reviewed literatures, and the outcomes were the proportion and risk of ILD related to anti-HER2 ADCs. A disproportionality analysis based on data from VigiBase was conducted to characterize the main features of anti-HER2 ADC-related ILD/pneumonitis.

Results

Two hundred and forty-five all-grade and 47 grade ≥ 3 ILD events with the proportion of 4.4% (95% confidence interval (CI) [2.0%, 6.8%]) and 0.5% (95% CI [0.3%, 0.8%]) were observed for anti-HER2 ADCs, respectively. Trastuzumab emtansine, trastuzumab deruxtecan and trastuzumab duocarmazine significantly increased the risk of all-grade and grade ≥ 3 ILD events with Peto odd ratios of 2.62 (95% CI [1.71, 4.04], P < 0.0001) and 2.82 (95% CI [1.07, 7.42], P = 0.04), respectively. In VigiBase, 271 cases of ILD/pneumonitis related to trastuzumab emtansine and trastuzumab deruxtecan were extracted. The median time to the onset of event was 86 days and 54.95% of events occurred within 3 months.

Conclusions

Trastuzumab emtansine, trastuzumab deruxtecan and trastuzumab duocarmazine increased the risk of ILD, which can lead to serious outcomes and tends to occur early.

KEYWORDS:

• Interstitial lung disease
• pneumonitis
• Anti-HER2 ADC
• trastuzumab emtansine
• trastuzumab deruxtecan

Acknowledgments

The supplied data from VigiBase come from various sources. The information does not represent the opinion of WHO. We thank the custom searches team at the Uppsala Monitoring Centre (Uppsala, Sweden) research section, without whom this study would not have been possible.

Declaration of Interests

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.

Author contributions

Zhuo Ma and Yi Zhang contributed equally to this work.

Conception: Yuhui Zhang, Zhuoling An.

Study design: Zhuo Ma, Yi Zhang, Yuhui Zhang, Zhuoling An.

Execution: Zhuo Ma, Yi Zhang, Min Zhu, Lin Feng.

Acquisition of data: Zhuo Ma, Yi Zhang, Min Zhu, Lin Feng.

Analysis: Zhuo Ma, Yi Zhang, Min Zhu, Lin Feng.

Interpretation: Zhuo Ma, Yi Zhang, Min Zhu, Lin Feng, Yuhui Zhang, Zhuoling An.

Draft or write the manuscript: Zhuo Ma, Yi Zhang.

All authors have reviewed and revised the manuscript, and have agreed to submit the article to Expert Review of Clinical Pharmacology. All authors agree to take responsibility and be accountable for the contents of the article and to share responsibility to resolve any questions raised about the accuracy or integrity of the published work.

Data sharing statement

The data that support the findings from the Vigibase platform. https://www.who-umc.org/vigibase/vigibase/. Restrictions apply to the availability of these data, which were used under license for this study. Thus, this data cannot be shared directly by the authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2022.2121705

Additional information

Funding

This paper was not funded.