Hyperprogressive Disease in Hepatocellular Carcinoma with Immune Checkpoint Inhibitor Use: A Case Series

Abstract

Immune checkpoint inhibitors (ICIs) have demonstrated promising results in a variety of advanced cancer types. The phenomenon of hyperprogressive disease (HPD) has only been documented in recent years, however, there have been no reports of HPD in hepatocellular carcinoma. We present a case series of six patients with advanced hepatocellular carcinoma treated with ICIs who demonstrated rapid radiological progression, this was confirmed by comparing tumor growth rates before and during treatment with HPD defined as tumor growth rate_ratio ≥2. Although ICIs have demonstrated profound efficacy in advanced cancer, they might also be responsible for HPD in a small subset of patients. The ability to predict treatment response to ICI is thus of importance in protecting patients from the deleterious effects of HPD.

Keywords::

• anti-PD-1
• Hepatocellular carcinoma
• hyperprogression
• immune checkpoint inhibitors
• immunotherapeutic agents
• immunotherapy
• pseudoprogression
• tumor growth rate

Ethical conduct of research

Institutional review board approval (SingHealth Centralised Institutional Review Board B- Ref: 2008/456/B) was obtained for this study. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Financial & competing interests disclosure

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

SP Choo found that some of her patients showed rapid deterioration following immunotherapy and suggested writing the manuscript. DJ Wong analysed the data and wrote the first draft of the manuscript. J Lee provided the case histories and edited the first draft. DJ Wong and T Hennedige reviewed the images and drew target lesions. SP Choo and CH Thng provided guidance and helped in editing the manuscript. T Hennedige made final editions to the manuscript.