Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody.

Abstract

BACKGROUND:

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) are used for the treatment of various cancer types. However, immune-related adverse events (irAEs) occur in patients treated with ICIs. Several small-scale studies have reported the onset of irAEs and therapeutic effects of ICIs. Here we report a large-scale retrospective study covering a wide range of cancers. We evaluated irAEs and the therapeutic effects of ICIs and determined whether irAEs could be predicted.

METHODS:

This study included patients treated with the anti-PD-1 antibodies nivolumab or pembrolizumab at Fujita Health University Hospital between December 2015 and March 2019. We retrospectively reviewed the electronic medical records for age, cancer type, pre-treatment blood test data, presence or absence of irAE onset, type and severity of irAEs, outcome of irAE treatment, response rate, progression-free survival and overall survival.

RESULTS:

Two hundred-eighty patients received ICIs. The overall incidence of irAEs was 41.1% (115 patients), and the incidence of severe irAEs of grade 3 and higher was 2.8% (eight patients). The most common irAEs were skin disorders, thyroid disorders and interstitial pneumonitis. Patients with irAEs were significantly older than those without irAEs (69.7 versus 66.0 years, P = 0.02). The objective response rate (ORR) in patients with irAEs was 30.4%, which was significantly higher than in patients without irAEs (12.7%; P < 0.01). Both the median overall and progression-free survival were significantly longer in patients with irAEs (P < 0.01, p < 0.01). Based on the blood test data obtained before ICI therapy, hypothyroidism, thyroid-stimulating hormone levels and thyroglobulin antibody levels were associated with the onset of irAEs. In many patients with irAEs of Common Terminology Criteria for Adverse Events Grade 3 or higher, re-administration of ICIs was difficult, and their outcomes were poor. In contrast, many patients with irAEs of a lower grade were able to resume ICI therapy.

CONCLUSION:

Although the onset of irAEs was difficult to be predicted based on pre-treatment tests. It appeared that the continuation of ICI therapy, along with early detection and adequate control of irAEs, might contribute to the improved prognosis of patients.

• Authors: Hiroshi Matsuoka, Takahiro Hayashi, Karen Takigami, Kazuyoshi Imaizumi, Ryoichi Shiroki, Naoki Ohmiya, Kazumitsu Sugiura, Kenji Kawada, Akira Sawaki, Koutaro Maeda, Yousuke Ando, Ichiro Uyama
• Journal: BMC cancer (BMC Cancer) Vol. 20 Issue 1 Pg. 656 (Jul 14 2020) ISSN: 1471-2407 [Electronic] England
• PMID: 32664888 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Nivolumab
• pembrolizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Drug-Related Side Effects and Adverse Reactions (epidemiology, etiology, pathology)
• Female
• Follow-Up Studies
• Humans
• Incidence
• Japan (epidemiology)
• Male
• Middle Aged
• Neoplasms (drug therapy, immunology, pathology)
• Nivolumab (administration & dosage)
• Prognosis
• Programmed Cell Death 1 Receptor (antagonists & inhibitors)
• Retrospective Studies
• Survival Rate
• Young Adult