TY - JOUR
T1 - Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors among Patients Aged 80 Years or Older with Cancer
T2 - A Multicenter International Cohort Study
AU - Nebhan, Caroline A.
AU - Cortellini, Alessio
AU - Ma, Weijie
AU - Ganta, Teja
AU - Song, Haocan
AU - Ye, Fei
AU - Irlmeier, Rebecca
AU - Debnath, Neha
AU - Saeed, Anwaar
AU - Radford, Maluki
AU - Alahmadi, Asrar
AU - Diamond, Akiva
AU - Hoimes, Christopher
AU - Ramaiya, Nikhil
AU - Presley, Carolyn J.
AU - Owen, Dwight H.
AU - Abou Alaiwi, Sarah
AU - Nassar, Amin
AU - Ricciuti, Biagio
AU - Lamberti, Giuseppe
AU - Bersanelli, Melissa
AU - Casartelli, Chiara
AU - Buti, Sebastiano
AU - Marchetti, Paolo
AU - Giusti, Raffaele
AU - Filetti, Marco
AU - Vanella, Vito
AU - Mallardo, Domenico
AU - Macherla, Shravanti
AU - Sussman, Tamara A.
AU - Botticelli, Andrea
AU - Galetta, Domenico
AU - Catino, Annamaria
AU - Pizzutilo, Pamela
AU - Genova, Carlo
AU - Dal Bello, Maria Giovanna
AU - Kalofonou, Foteini
AU - Daniels, Ella
AU - Ascierto, Paolo A.
AU - Pinato, David J.
AU - Choueiri, Toni K.
AU - Johnson, Douglas B.
AU - Marron, Thomas U.
AU - Wang, Yinghong
AU - Naqash, Abdul Rafeh
N1 - Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - Importance: Geriatric (aged ≥80 years) patients are historically underrepresented in cancer clinical trials. Little is known about the efficacy of immune checkpoint inhibitors (ICIs) in geriatric patients. These agents are associated with immune-related adverse events (irAEs), which may be particularly associated with morbidity in this population. Objective: To provide insight into the clinical outcomes and safety of ICIs among geriatric patients (aged ≥80 years) with cancer. Design, Setting, and Participants: A Multicenter, international retrospective study of 928 geriatric patients with different tumors treated with single-agent ICIs between 2010 to 2019 from 18 academic centers in the US and Europe. Analyses were conducted from January 2021 to April 2021. Main Outcomes and Measures: Clinical outcomes and irAE patterns in geriatric patients treated with single-agent ICIs. Results: Median (range) age of the 928 patients at ICI initiation was 83.0 (75.8-97.0) years. Most patients (806 [86.9%]) were treated with anti-programmed cell death 1 therapy. Among the full cohort, the 3 most common tumors were non-small cell lung cancer (NSCLC, 345 [37.2%]), melanoma (329 [35.5%]), and genitourinary (GU) tumors (153 [16.5%]). Objective response rates for patients with NSCLC, melanoma, and GU tumors were 32.2%, 39.3%, and 26.2%, respectively. Median PFS and OS, respectively, were 6.7 and 10.9 months (NSCLC), 11.1 and 30.0 months (melanoma), and 6.0 and 15.0 months (GU). Within histologically specific subgroups (NSCLC, melanoma, and GU), clinical outcomes were similar across age subgroups (aged <85 vs ≥85 years). Among all 928 patients, 383 (41.3%) experienced ≥1 irAE(s), including 113 (12.2%) that were reported to be grade (G) 3 to 4 based on Common Terminology Criteria for Adverse Events (version 5.0). The median time to irAE onset was 9.8 weeks; 219 (57%) occurred within the first 3 months after ICI initiation. Discontinuation of treatment with ICIs owing to irAEs occurred in 137 (16.1%) patients. There was no significant difference in the rate of irAEs among patients aged younger than 85, 85 to 89, and 90 years or older. Despite the similar rate of G3 or higher irAEs, ICIs were discontinued due to irAEs more than twice as often among patients aged 90 years or older compared with patients younger than 90 years (30.9% vs 15.1%, P =.008). Conclusions and Relevance: The findings of this international cohort study suggest that treatment with ICIs may be effective and generally well tolerated among older patients with cancer, though ICI discontinuation owing to irAEs was more frequent with increasing age.
AB - Importance: Geriatric (aged ≥80 years) patients are historically underrepresented in cancer clinical trials. Little is known about the efficacy of immune checkpoint inhibitors (ICIs) in geriatric patients. These agents are associated with immune-related adverse events (irAEs), which may be particularly associated with morbidity in this population. Objective: To provide insight into the clinical outcomes and safety of ICIs among geriatric patients (aged ≥80 years) with cancer. Design, Setting, and Participants: A Multicenter, international retrospective study of 928 geriatric patients with different tumors treated with single-agent ICIs between 2010 to 2019 from 18 academic centers in the US and Europe. Analyses were conducted from January 2021 to April 2021. Main Outcomes and Measures: Clinical outcomes and irAE patterns in geriatric patients treated with single-agent ICIs. Results: Median (range) age of the 928 patients at ICI initiation was 83.0 (75.8-97.0) years. Most patients (806 [86.9%]) were treated with anti-programmed cell death 1 therapy. Among the full cohort, the 3 most common tumors were non-small cell lung cancer (NSCLC, 345 [37.2%]), melanoma (329 [35.5%]), and genitourinary (GU) tumors (153 [16.5%]). Objective response rates for patients with NSCLC, melanoma, and GU tumors were 32.2%, 39.3%, and 26.2%, respectively. Median PFS and OS, respectively, were 6.7 and 10.9 months (NSCLC), 11.1 and 30.0 months (melanoma), and 6.0 and 15.0 months (GU). Within histologically specific subgroups (NSCLC, melanoma, and GU), clinical outcomes were similar across age subgroups (aged <85 vs ≥85 years). Among all 928 patients, 383 (41.3%) experienced ≥1 irAE(s), including 113 (12.2%) that were reported to be grade (G) 3 to 4 based on Common Terminology Criteria for Adverse Events (version 5.0). The median time to irAE onset was 9.8 weeks; 219 (57%) occurred within the first 3 months after ICI initiation. Discontinuation of treatment with ICIs owing to irAEs occurred in 137 (16.1%) patients. There was no significant difference in the rate of irAEs among patients aged younger than 85, 85 to 89, and 90 years or older. Despite the similar rate of G3 or higher irAEs, ICIs were discontinued due to irAEs more than twice as often among patients aged 90 years or older compared with patients younger than 90 years (30.9% vs 15.1%, P =.008). Conclusions and Relevance: The findings of this international cohort study suggest that treatment with ICIs may be effective and generally well tolerated among older patients with cancer, though ICI discontinuation owing to irAEs was more frequent with increasing age.
UR - http://www.scopus.com/inward/record.url?scp=85118984682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85118984682&partnerID=8YFLogxK
U2 - 10.1001/jamaoncol.2021.4960
DO - 10.1001/jamaoncol.2021.4960
M3 - Article
C2 - 34734989
AN - SCOPUS:85118984682
SN - 2374-2437
VL - 7
SP - 1856
EP - 1861
JO - JAMA Oncology
JF - JAMA Oncology
IS - 12
ER -