Safety and tolerability of PD-1/PD-L1 inhibitors in elderly and frail patients with advanced malignancies

Sakakida,Tomoki; Ishikawa,Takeshi; Uchino,Junji; Tabuchi,Yusuke; Komori,Satoshi; Asai,Jun; Arai,Akihito; Tsunezuka,Hiroaki; Kosuga,Toshiyuki; Konishi,Hirotaka; Hongo,Fumiya; Inoue,Masayoshi; Hirano,Shigeru; Ukimura,Osamu; Taguchi,Tetsuya; Takayama,Koichi; Itoh,Yoshito

doi:10.3892/ol.2020.11875

Safety and tolerability of PD-1/PD-L1 inhibitors in elderly and frail patients with advanced malignancies

Authors:
- Tomoki Sakakida
- Takeshi Ishikawa
- Junji Uchino
- Yusuke Tabuchi
- Satoshi Komori
- Jun Asai
- Akihito Arai
- Hiroaki Tsunezuka
- Toshiyuki Kosuga
- Hirotaka Konishi
- Fumiya Hongo
- Masayoshi Inoue
- Shigeru Hirano
- Osamu Ukimura
- Tetsuya Taguchi
- Koichi Takayama
- Yoshito Itoh
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Affiliations: Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan, Department of Pulmonary Medicine, Graduate School of Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan, Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan, Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan, Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan, Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan, Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan, Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan, Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
Published online on: July 15, 2020 https://doi.org/10.3892/ol.2020.11875
Article Number: 14
Copyright: © Sakakida et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The number of elderly patients with cancer has increased due to aging of the population. However, safety of programmed cell death‑1 (PD‑1) or programed cell death ligand 1 (PD‑L1) inhibitors in elderly patients remains controversial, and limited information exists in frail patients. The present study retrospectively identified 197 patients treated with nivolumab, pembrolizumab or atezolizumab for unresectable advanced cancer between September 2014 and December 2018. Patients were divided into the elderly (age, ≥75 years) and non‑elderly (age, <75 years) groups. The detailed immune‑related adverse events (irAE) profile and development of critical complications were evaluated. To assess tolerability, the proportion of patients who continued PD‑1/PD‑L1 inhibitor for >6 months was analyzed. In the two groups, a three‑element frailty score, including performance status, Charlson Comorbidity Index and neutrophil‑lymphocyte ratio, was estimated, and patients were divided into the low‑, intermediate‑ and high‑frailty subgroups. Safety and tolerability were evaluated using the aforementioned items. A total of 58 patients (29.4%) were aged ≥75 years. No significant difference was found in the development of irAEs, hospitalization and treatment discontinuation due to irAEs between the two groups. However, the occurrence of unexpected critical complications was significantly higher in the elderly group (P=0.03). Among the elderly patients with high frailty, more critical complications and fatal irAE (hepatitis) were observed. In this population, 33.3% were able to continue treatment for >6 months without disease progression. The present analysis based on real world data showed similar safety and tolerability of PD‑1/PD‑L1 inhibitors in elderly patients with advanced malignancies. However, the impact of irAE in elderly patients, especially those with frailty, was occasionally greater compared with that in younger and fit patients.

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