Inclusion, characteristics, and reporting of older adults in FDA registration studies of immunotherapy, 2018-2022

Abstract

Immune checkpoint inhibitors (ICI) have transformed the management of cancer, particularly for older adults, who constitute a majority of the global cancer patient population. This study aimed to assess the inclusion, characteristics, and reporting of older adults enrolled in Food and Drug Administration (FDA) registration clinical trials of ICI between 2018 and 2022. Clinical trials of ICI leading to an FDA approval in solid tumor oncology between 2018 and 2022 were included. Primary study reports and all available secondary publications were assessed. The availability and completeness of older subgroup data for protocol-defined clinical efficacy endpoints, health-related quality of life (HRQOL) and toxicity outcomes, and baseline characteristics were assessed according to predefined criteria which categorized reporting completeness hierarchically in relation to the availability of published data, including effect size, sample size, and measures of precision. 53 registration trials were included, involving a total of 37,094 participants. Most trials (64.2%) were of ICI combination therapy. 42.3% of patients were aged≥65 years; 11.1% were aged≥75. No trials specified an upper age limit for eligibility. 98.1% of trials excluded patients with European Cooperative Oncology Group performance status>1. 87.2% of primary efficacy endpoints and 17.9% of secondary efficacy endpoints were reported completely for older adults. Five studies (9.4%) reported baseline characteristics, three (6.1%) reported HRQOL assessments, and four (7.5%) reported toxicity outcomes completely among older subgroups. No trials conducted baseline geriatric assessments or reported geriatric-specific symptoms or quality of life scales. This analysis highlights significant deficits in the enrollment and reporting of older subgroups in pivotal trials of ICI therapy. The findings highlight an urgent need for improved reporting and inclusion standards in clinical trials of ICI to better inform treatment decisions for older adults.

Keywords: Geriatric; Immune Checkpoint Inhibitor; Immunotherapy.

Figure 1. Study flow diagram. FDA, Food and Drug Administration.

Figure 2. Completeness of reporting of older subgroups according to individual trials. APF, alive and progression-free; BOR, best overall response; CRR, complete response rate; DCR, disease control rate; DFS, disease-free survival; DMFS, distant metastasis-free survival; DOR, duration of response; DRSS1, disease recurrence-specific survival 1; DRSS2, disease recurrence–specific survival 2; DSS, disease-specific survival; EFS, event-free survival; HRQOL, health-related quality of life; Max%, maximum percent change from baseline in the sum of diameters of the target lesion; MPR, major pathological response; NUTRFS, non-urothelial tract recurrence-free survival; ORR, objective response rate; OS, overall survival; pCR, pathologic complete response; PFS, progression-free survival; PFS2, progression-free survival 2; RFS, recurrence-free survival; TTDM, time to distant metastasis; TTP, time to progression; TTR, time to response.