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 language | English |
|---|---|
| Journal | Acta Oncologica |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2019 |
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ASJC Scopus subject areas
- Hematology
- Oncology
- Radiology Nuclear Medicine and imaging
Cite this
Influence of age on the efficacy of immune checkpoint inhibitors in advanced cancers : a systematic review and meta-analysis. / Ninomiya, Kiichiro; Oze, Isao; Kato, Yuka; Kubo, Toshio; Ichihara, Eiki; Rai, Kammei; Ohashi, Kadoaki; Kozuki, Toshiyuki; Tabata, Masahiro; Maeda, Yoshinobu; Kiura, Katsuyuki; Hotta, Katsuyuki.
In: Acta Oncologica, 01.01.2019.Research output: Contribution to journal › Review article
}
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 -