Immunotherapy in the Elderly

Abstract

Context: Immunotherapy has historic and contemporary presence in prostate, urothelial (UC), and renal cell (RCC) carcinomas. However, robust data on utility and generalizability of these treatments in older patients are lacking.

Objective: To systematically evaluate evidence regarding the efficacy and safety of immunotherapy in elderly patients with prostate cancer, UC, or RCC.

Evidence acquisition: PubMed/Medline, Embase, Web of Knowledge, and Cochrane Library databases were searched up to October 2017 and according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. A narrative review of studies was performed.

Evidence synthesis: Twenty-one reports were included regarding prostate cancer (four studies), UC (eight), and RCC (nine). In prostate cancer, sipuleucel-T improves survival (median age >70 yr) and similar results were seen in the PROSTVAC phase 2 trial. Ipilimumab has not improved survival independent of age; data for programmed cell death 1 inhibition is evolving. In metastatic UC, ≥50% of patients enrolled in pivotal checkpoint inhibitor studies were aged ≥65 yr. Three studies reported similar objective response rates (ORRs) in patients aged <65 versus ≥65 yr, whereas one study reported comparable ORRs in patients <80 versus ≥80 yr. In metastatic RCC, cytokine studies showed no efficacy difference by age; one study reported more ≥grade 3 toxicity in patients aged ≥65 yr. One vaccine-based study suggests that older age was associated with shorter survival. The benefit of nivolumab in second-line therapy was more apparent for patients aged 65-<75 yr than for those aged ≥75 yr. Across tumor subtypes, immunotherapy was well tolerated with minimal data stratifying toxicity by age.

Conclusions: Contemporary immunotherapy has informed practice in genitourinary malignancies independent of patient age. Trial reporting of outcomes by age will be important to understand the generalizability of ongoing investigations for elderly patients.

Patient summary: With the growing use of immunotherapy in genitourinary malignancies, benefits appear to apply independent of age. As the field advances, detailed reporting on outcomes and toxicities by age will be informative for both patients and physicians when discussing treatment options.

Keywords: Ageing; Bladder cancer; Elderly; Immunotherapy; Kidney cancer; Prostate cancer.