Peripheral neuropathy and headache in cancer patients treated with immunotherapy and immuno-oncology combinations: the MOUSEION-02 study

ABSTRACT

Introduction

Treatment-related neurotoxicity is a common side effect in cancer patients. However, few data are available regarding the risk of several neurotoxicities in patients treated with immune checkpoint inhibitors.

Areas covered

The MOUSEION-02 study is an up-to-date meta-analysis aimed at assessing the risk of peripheral neuropathy, peripheral sensory neuropathy, and headache in cancer patients receiving immunotherapy and immuno-oncology combinations. Patients receiving immunotherapy (as monotherapy or in combination with other anticancer agents) showed lower risk of all-grade peripheral neuropathy (RR, 0.50; 95% CI, 0.35–0.70) and all-grade peripheral sensory neuropathy (RR, 0.49; 95% CI, 0.30–0.79). Similarly, in patients treated with immune checkpoint inhibitor monotherapy, we observed lower risk of all-grade peripheral neuropathy (RR, 0.05; 95% CI, 0.03–0.10) and all-grade peripheral sensory neuropathy (RR, 0.11; 95% CI, 0.05–0.23). No differences were observed in terms of all-grade headache.

Expert opinion

Although the results of this meta-analysis should be interpreted with caution due to several issues, our study draws attention to immunotherapy-related neurotoxicity with the aim of maximizing clinical outcomes of cancer patients experiencing these not uncommon, and yet poorly studied, adverse events.

KEYWORDS:

• Atezolizumab
• avelumab
• cancer
• headache
• immunotherapy
• meta-analysis
• nivolumab
• pembrolizumab
• peripheral neuropathy
• peripheral sensory neuropathy

Article highlights

• Immune checkpoint inhibitors have been associated with a range of side effects, including gastrointestinal, cutaneous, hepatic, and endocrine toxicities.

• Nonetheless, few data are available regarding the risk of certain neurotoxicities in this setting, including peripheral neuropathy and headache, with no meta-analysis in literature specifically focused on this timely, and yet poorly studied, topic.

• Herein, we conducted a meta-analysis aimed at systematically exploring the risk of all-grade peripheral neuropathy, peripheral sensory neuropathy, and headache in cancer patients treated with immunotherapy and immuno-oncology combinations.

• The current meta-analysis tackles this important and under-discussed topic, by using published aggregated data from 29 randomized phase III clinical trials including 18,694 cancer patients.

• Neurological toxicities including peripheral neuropathy, peripheral sensory neuropathy, and headache in patients treated with immunotherapy and immuno-oncology combinations remain an important and under-reported issue in cancer immunotherapy.

• Although the results of this meta-analysis should be interpreted with caution due to several issues and limitations, our study highlights the importance to pay particular attention to immunotherapy-related neurotoxicity, with the aim of maximizing clinical outcomes of cancer patients receiving immune checkpoint inhibitors.

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

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

Author contributions

M Santoni and F Massari contributed to the study concept and design; A Rizzo, V Mollica, M Rosellini, and A Marchetti contributed to the acquisition of data; all authors contributed to the data analysis and interpretation; A Rizzo, M Santoni, V Mollica, and F Massari contributed to the drafting of the manuscript; all authors contributed to the critical revision of the manuscript for important intellectual content; A Rizzo, M Santoni, V Mollica, and F Massari contributed to the statistical analysis; A Rizzo, V Mollica, F Massari, and M Santoni provided administrative, technical, or materials support; and M Santoni, F Logullo, L Faloppi, N Battelli, and F Massari provided supervision.

Supplementary material

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Additional information

Funding

This paper was not funded.