Influence of age on the efficacy of immune checkpoint inhibitors in advanced cancers: a systematic review and meta-analysis

Research output: Contribution to journalReview article

Abstract

Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer treatment. However, it remains to be clarified whether the benefits that they confer differ according to patient age. We conducted a systematic review and meta-analysis to assess age differences in the benefits of ICI treatment. Methods: We systematically searched the PubMed database for randomised controlled trials of ICIs, including PD-1, PD-L1 and CTLA-4 inhibitors across multiple cancer types, such as melanoma, lung cancer and gastric cancer. We extracted trials including hazard ratios (HRs) for death stratified by patient age (cut-off age, 65 years). The primary objective of this study was to assess the difference in ICI efficacy between younger and older patients. We calculated pooled HRs and 95% confidence intervals (CIs) for younger and older cancer patients, and assessed data heterogeneity. Results: We identified 3999 studies in our search. Of these, 24 eligible randomised trials, including a total of 8157 (57%) younger and 6104 (43%) older cancer patients, fulfilled the criteria for our study and were thus further analysed. The pooled HRs of the younger and older patients were 0.76 (95% CI: 0.69–0.84) and 0.80 (95% CI: 0.71–0.86), respectively; the difference in ICI efficacy between younger and older cancer patients was not significant (p =.82). Regarding the PD-1 and PD-L1 inhibitors, the survival benefit was similar in both age groups (HR: 0.74; p =.96), whereas for the CTLA-4 inhibitors, there tended to be less survival benefit for older versus younger patients (HR: 0.90 and 0.77, respectively; p =.26). Conclusions: The survival benefit conferred by ICI was not age-dependent, amongst patients aged 65 years or younger. However, age-dependent benefits may vary amongst different types of ICIs.

Original languageEnglish
JournalActa Oncologica
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Meta-Analysis
Neoplasms
Confidence Intervals
Stomach Neoplasms
Survival
PubMed
Melanoma
Lung Neoplasms
Randomized Controlled Trials
Age Groups
Databases
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

@article{3e62766eb3504385b1dd33c1e910fee1,
title = "Influence of age on the efficacy of immune checkpoint inhibitors in advanced cancers: a systematic review and meta-analysis",
abstract = "Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer treatment. However, it remains to be clarified whether the benefits that they confer differ according to patient age. We conducted a systematic review and meta-analysis to assess age differences in the benefits of ICI treatment. Methods: We systematically searched the PubMed database for randomised controlled trials of ICIs, including PD-1, PD-L1 and CTLA-4 inhibitors across multiple cancer types, such as melanoma, lung cancer and gastric cancer. We extracted trials including hazard ratios (HRs) for death stratified by patient age (cut-off age, 65 years). The primary objective of this study was to assess the difference in ICI efficacy between younger and older patients. We calculated pooled HRs and 95{\%} confidence intervals (CIs) for younger and older cancer patients, and assessed data heterogeneity. Results: We identified 3999 studies in our search. Of these, 24 eligible randomised trials, including a total of 8157 (57{\%}) younger and 6104 (43{\%}) older cancer patients, fulfilled the criteria for our study and were thus further analysed. The pooled HRs of the younger and older patients were 0.76 (95{\%} CI: 0.69–0.84) and 0.80 (95{\%} CI: 0.71–0.86), respectively; the difference in ICI efficacy between younger and older cancer patients was not significant (p =.82). Regarding the PD-1 and PD-L1 inhibitors, the survival benefit was similar in both age groups (HR: 0.74; p =.96), whereas for the CTLA-4 inhibitors, there tended to be less survival benefit for older versus younger patients (HR: 0.90 and 0.77, respectively; p =.26). Conclusions: The survival benefit conferred by ICI was not age-dependent, amongst patients aged 65 years or younger. However, age-dependent benefits may vary amongst different types of ICIs.",
author = "Kiichiro Ninomiya and Isao Oze and Yuka Kato and Toshio Kubo and Eiki Ichihara and Kammei Rai and Kadoaki Ohashi and Toshiyuki Kozuki and Masahiro Tabata and Yoshinobu Maeda and Katsuyuki Kiura and Katsuyuki Hotta",
year = "2019",
month = "1",
day = "1",
doi = "10.1080/0284186X.2019.1695062",
language = "English",
journal = "Acta Oncologica",
issn = "0284-186X",
publisher = "Informa Healthcare",

}

TY - JOUR

T1 - Influence of age on the efficacy of immune checkpoint inhibitors in advanced cancers

T2 - a systematic review and meta-analysis

AU - Ninomiya, Kiichiro

AU - Oze, Isao

AU - Kato, Yuka

AU - Kubo, Toshio

AU - Ichihara, Eiki

AU - Rai, Kammei

AU - Ohashi, Kadoaki

AU - Kozuki, Toshiyuki

AU - Tabata, Masahiro

AU - Maeda, Yoshinobu

AU - Kiura, Katsuyuki

AU - Hotta, Katsuyuki

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer treatment. However, it remains to be clarified whether the benefits that they confer differ according to patient age. We conducted a systematic review and meta-analysis to assess age differences in the benefits of ICI treatment. Methods: We systematically searched the PubMed database for randomised controlled trials of ICIs, including PD-1, PD-L1 and CTLA-4 inhibitors across multiple cancer types, such as melanoma, lung cancer and gastric cancer. We extracted trials including hazard ratios (HRs) for death stratified by patient age (cut-off age, 65 years). The primary objective of this study was to assess the difference in ICI efficacy between younger and older patients. We calculated pooled HRs and 95% confidence intervals (CIs) for younger and older cancer patients, and assessed data heterogeneity. Results: We identified 3999 studies in our search. Of these, 24 eligible randomised trials, including a total of 8157 (57%) younger and 6104 (43%) older cancer patients, fulfilled the criteria for our study and were thus further analysed. The pooled HRs of the younger and older patients were 0.76 (95% CI: 0.69–0.84) and 0.80 (95% CI: 0.71–0.86), respectively; the difference in ICI efficacy between younger and older cancer patients was not significant (p =.82). Regarding the PD-1 and PD-L1 inhibitors, the survival benefit was similar in both age groups (HR: 0.74; p =.96), whereas for the CTLA-4 inhibitors, there tended to be less survival benefit for older versus younger patients (HR: 0.90 and 0.77, respectively; p =.26). Conclusions: The survival benefit conferred by ICI was not age-dependent, amongst patients aged 65 years or younger. However, age-dependent benefits may vary amongst different types of ICIs.

AB - Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer treatment. However, it remains to be clarified whether the benefits that they confer differ according to patient age. We conducted a systematic review and meta-analysis to assess age differences in the benefits of ICI treatment. Methods: We systematically searched the PubMed database for randomised controlled trials of ICIs, including PD-1, PD-L1 and CTLA-4 inhibitors across multiple cancer types, such as melanoma, lung cancer and gastric cancer. We extracted trials including hazard ratios (HRs) for death stratified by patient age (cut-off age, 65 years). The primary objective of this study was to assess the difference in ICI efficacy between younger and older patients. We calculated pooled HRs and 95% confidence intervals (CIs) for younger and older cancer patients, and assessed data heterogeneity. Results: We identified 3999 studies in our search. Of these, 24 eligible randomised trials, including a total of 8157 (57%) younger and 6104 (43%) older cancer patients, fulfilled the criteria for our study and were thus further analysed. The pooled HRs of the younger and older patients were 0.76 (95% CI: 0.69–0.84) and 0.80 (95% CI: 0.71–0.86), respectively; the difference in ICI efficacy between younger and older cancer patients was not significant (p =.82). Regarding the PD-1 and PD-L1 inhibitors, the survival benefit was similar in both age groups (HR: 0.74; p =.96), whereas for the CTLA-4 inhibitors, there tended to be less survival benefit for older versus younger patients (HR: 0.90 and 0.77, respectively; p =.26). Conclusions: The survival benefit conferred by ICI was not age-dependent, amongst patients aged 65 years or younger. However, age-dependent benefits may vary amongst different types of ICIs.

UR - http://www.scopus.com/inward/record.url?scp=85075715645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075715645&partnerID=8YFLogxK

U2 - 10.1080/0284186X.2019.1695062

DO - 10.1080/0284186X.2019.1695062

M3 - Review article

AN - SCOPUS:85075715645

JO - Acta Oncologica

JF - Acta Oncologica

SN - 0284-186X

ER -