Open AccessImmune‐Related Adverse Events by Immune Checkpoint Inhibitors Significantly Predict Durable Efficacy Even in Responders with Advanced Non‐Small Cell Lung Cancer
Author(s) -
Akamatsu Hiroaki,
Murakami Eriko,
Oyanagi Jun,
Shibaki Ryota,
Kaki Takahiro,
Takase Eri,
Tanaka Masanori,
Harutani Yuhei,
Yamagata Nao,
Okuda Yuka,
Furuta Katsuyuki,
Sugimoto Takeya,
Teraoka Shunsuke,
Hayata Atsushi,
Tokudome Nahomi,
Ozawa Yuichi,
Mori Keita,
Koh Yasuhiro,
Yamamoto Nobuyuki
Publication year - 2020
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2019-0299
Subject(s) - medicine , hazard ratio , adverse effect , lung cancer , confidence interval , immune system , biomarker , oncology , prospective cohort study , immunology , chemistry , biochemistry
Background Although predictive value of immune‐related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been suggested by several studies, their assessments were insufficient because patients were categorized only by the occurrence of irAEs. It has not been elucidated whether irAEs also play a significant role even in responders. Materials and Methods Between December 2015 and September 2018, 106 patients with advanced non‐small cell lung cancer treated with ICIs were enrolled in our prospective biomarker study. Twenty‐three of these were responders, defined as those with complete or partial response. We investigated the proportion of irAEs among overall and responders. For responders, progression‐free survival (PFS) and overall survival of ICIs were compared between those with and without irAEs. As an exploratory analysis, we measured 41 proteins from peripheral blood before and after ICI treatment. Results The proportion of irAEs was significantly higher in responders than nonresponders (65.2% vs. 19.3%, p < .01). Among responders, clinical characteristics did not differ regardless of the occurrence of irAEs. However, there was a significant difference in PFS among responders (irAE group 19.1 months vs. non‐irAE group 5.6 months; hazard ratio: 0.30 [95% confidence interval: 0.10–0.85]; p = .02). Of 41 protein analyses, fibroblast growth factor‐2 at baseline and monocyte chemoattractant protein fold change showed significant differences between them ( p < .04). Conclusion Although this is a small sample–sized study, irAE might be a predictive factor of durable efficacy, even in patients who responded to ICIs. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI. Implications for Practice Although the predictive value of immune‐related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) has been suggested by several studies, it has not been elucidated whether irAEs also play a significant role even in responders. This study showed that more than 60% of responders had irAEs. It demonstrated the strong correlation between irAEs and efficacy even in responders. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.