Inclusion, Characteristics, and Reporting of Older Adults in FDA Registration Studies of Immunotherapy, 2018-2022

Overview

Journal J Immunother Cancer

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2024 Aug 29

PMID 39209450

Authors

Colm Mac Eochagain

Robert Power

Christine Sam

Nicolas M Gonzalez-Senac

Darren Walsh

Mukul Roy

Nicolo Matteo Luca Battisti

Affiliations

Soon will be listed here.

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.

References

Zhang L, Sun L, Yu J, Shan F, Zhang K, Pang X . Comparison of Immune Checkpoint Inhibitors between Older and Younger Patients with Advanced or Metastatic Lung Cancer: A Systematic Review and Meta-Analysis. Biomed Res Int. 2019; 2019:9853701. PMC: 6535828. DOI: 10.1155/2019/9853701. View

Rini B, Plimack E, Stus V, Gafanov R, Hawkins R, Nosov D . Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019; 380(12):1116-1127. DOI: 10.1056/NEJMoa1816714. View

Broderick J, Hussey J, Kennedy M, O Donnell D . Patients over 65 years are assigned lower ECOG PS scores than younger patients, although objectively measured physical activity is no different. J Geriatr Oncol. 2014; 5(1):49-56. DOI: 10.1016/j.jgo.2013.07.010. View

Coder B, Wang H, Ruan L, Su D . Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation. J Immunol. 2015; 194(12):5825-37. PMC: 4458423. DOI: 10.4049/jimmunol.1500082. View

Wang D, Salem J, Cohen J, Chandra S, Menzer C, Ye F . Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018; 4(12):1721-1728. PMC: 6440712. DOI: 10.1001/jamaoncol.2018.3923. View

Magee D, Hird A, Klaassen Z, Sridhar S, Nam R, Wallis C . Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials. Ann Oncol. 2020; 31(1):50-60. DOI: 10.1016/j.annonc.2019.10.008. View

Thomas R, Wang W, Su D . Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging. Immun Ageing. 2020; 17:2. PMC: 6971920. DOI: 10.1186/s12979-020-0173-8. View

Daste A, Domblides C, Gross-Goupil M, Chakiba C, Quivy A, Cochin V . Immune checkpoint inhibitors and elderly people: A review. Eur J Cancer. 2017; 82:155-166. DOI: 10.1016/j.ejca.2017.05.044. View

Elias R, Giobbie-Hurder A, McCleary N, Ott P, Hodi F, Rahma O . Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis. J Immunother Cancer. 2018; 6(1):26. PMC: 5885356. DOI: 10.1186/s40425-018-0336-8. View

10.

Choueiri T, Powles T, Burotto M, Escudier B, Bourlon M, Zurawski B . Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021; 384(9):829-841. PMC: 8436591. DOI: 10.1056/NEJMoa2026982. View

11.

BrintzenhofeSzoc K, Krok-Schoen J, Canin B, Parker I, MacKenzie A, Koll T . The underreporting of phase III chemo-therapeutic clinical trial data of older patients with cancer: A systematic review. J Geriatr Oncol. 2020; 11(3):369-379. PMC: 7412117. DOI: 10.1016/j.jgo.2019.12.007. View

12.

Li D, Toh H, Merle P, Tsuchiya K, Hernandez S, Verret W . Atezolizumab plus Bevacizumab versus Sorafenib for Unresectable Hepatocellular Carcinoma: Results from Older Adults Enrolled in the IMbrave150 Randomized Clinical Trial. Liver Cancer. 2023; 11(6):558-571. PMC: 9801180. DOI: 10.1159/000525671. View

13.

Godby R, Johnson D, Williams G . Immunotherapy in Older Adults with Cancer. Curr Oncol Rep. 2019; 21(7):56. PMC: 6619507. DOI: 10.1007/s11912-019-0806-2. View

14.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

15.

Wildiers H, de Glas N . Anticancer drugs are not well tolerated in all older patients with cancer. Lancet Healthy Longev. 2022; 1(1):e43-e47. DOI: 10.1016/S2666-7568(20)30001-5. View

16.

Tomasik B, Bienkowski M, Braun M, Popat S, Dziadziuszko R . Effectiveness and safety of immunotherapy in NSCLC patients with ECOG PS score ≥2 - Systematic review and meta-analysis. Lung Cancer. 2021; 158:97-106. DOI: 10.1016/j.lungcan.2021.06.004. View

17.

Booth C, Sengar M, Goodman A, Wilson B, Aggarwal A, Berry S . Common Sense Oncology: outcomes that matter. Lancet Oncol. 2023; 24(8):833-835. DOI: 10.1016/S1470-2045(23)00319-4. View

18.

Tomita Y, Motzer R, Choueiri T, Rini B, Miyake H, Uemura H . Efficacy and safety of avelumab plus axitinib in elderly patients with advanced renal cell carcinoma: extended follow-up results from JAVELIN Renal 101. ESMO Open. 2022; 7(2):100450. PMC: 9058903. DOI: 10.1016/j.esmoop.2022.100450. View

19.

Dotan E, Walter L, Browner I, Clifton K, Cohen H, Extermann M . NCCN Guidelines® Insights: Older Adult Oncology, Version 1.2021. J Natl Compr Canc Netw. 2021; 19(9):1006-1019. DOI: 10.6004/jnccn.2021.0043. View

20.

Socinski M, Ozguroglu M, Villegas A, Daniel D, Vicente D, Murakami S . Durvalumab After Concurrent Chemoradiotherapy in Elderly Patients With Unresectable Stage III Non-Small-Cell Lung Cancer (PACIFIC). Clin Lung Cancer. 2021; 22(6):549-561. DOI: 10.1016/j.cllc.2021.05.009. View