Advanced age is an important risk factor of cancer and is associated with poor prognosis. Changes in the immune system called immunosenescence may occur with older age. However, the impact of aging on efficacy and safety of immune checkpoint inhibitors (ICI), such as anti-PD(L)1, remains undetermined.
Patients with advanced solid tumours treated with an anti-PD(L)1 agent monotherapy between June 2014 and October 2017 and prospectively included within the Gustave Roussy ICI-dedicated pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie) were retrospectively reviewed. Incidence of immune-related adverse events (irAEs) of grade ≥2 was compared between patients aged ≥ 70 and < 70 years old using Chi-squared test.
Among the 615 patients included in the analysis, 191 were ≥ 70 years old (OP) and 424 < 70 years old (YP). The median age of OP and YP were respectively 77 (70 - 93) and 59 (17 - 69). A total of 165 irAEs were included in the analysis (103 Grade 2 and 58 Grade 3-4). The overall occurrence of irAEs grade ≥ 2 was higher in OP compared to YP (33% versus 25%, p = 0.03). Statistical significance was lost when stratifying irAEs according to their severity grade, suggesting that this effect was constant whatever the grade (p = 0.08 for Grade 2 and p = 0.13 for Grade 3-4). Anti-PD(L)1-related deaths were registered in 1 OP and 3 YP (0.5% and 0.7% respectively; NS). The most frequent organs toxicities in OP were skin rash (49%), endocrine (14%), hepatic (10%); it was skin rash (28%), endocrine (25%), digestive (15%) in YP. Median time to toxicity was similar between the two groups (7 weeks in YP and 6 weeks in OP, p = 0.31).
Anti-PD(L)1 immunotherapies are an acceptable treatment option for OPs, by being aware that immune related adverse events are more frequent in this population. Further dedicated studies are warranted to explore prospectively immune-related safety in OPs. Impact: Older patients should be monitored closely as they may be at risk of increased significant immune-related toxicity compared to their younger counterparts.
Clinical trial identification
Legal entity responsible for the study
Has not received any funding.
S. Champiat: Consulting: AstraZeneca, BMS, MSD, Roche, Janssen, Novartis. J-C. Soria: Employee: AstraZeneca Medimmune; Honoraria, Advisory role: Astex, Clovis, GSK, Gammamabs, Lilly, MSD, Merus, Pfizer, Pharmamar, Pierre Fabre, Roche Genentech, Sanofi, Servier, Takeda. C. Massard: Honoraria, Consultancy fees: Sanofi, Janssen, Astellas, Genetech, Orion, Medimmune, Ipsen. A. Marabelle: Honoraria, Consultancy fees: AstraZeneca, BMS, Merck, Sanofi, Janssen, Astellas, Genetech, Orion, Medimmune, Ipsen. All other authors have declared no conflicts of interest.