Phase 3 Trials Demonstrate Efficacy of Immune Checkpoint Inhibitors for Lung Cancer in Older Adults

Commentary
Article

Older patients’ underrepresentation in clinical trials leaves a gap in data regarding appropriate treatment.

Lung cancer causes more deaths than any other type of cancer.1 Eighty-five percent of cases are specifically non-small cell lung cancer (NSCLC), which primarily affects the geriatric population.2 Despite such prevalence, older patients’ underrepresentation in clinical trials leaves a gap in data regarding appropriate treatment.1

Immune checkpoint inhibitors (ICIs) are a common, life-prolonging NSCLC therapy. This class comprises PD-1, PD-L1, and CTLA-4 checkpoint inhibitors. Anti-PD-1 agents approved by the FDA include pembrolizumab and nivolumab, FDA-approved anti-PD-L1 monoclonal antibodies include atezolizumab and durvalumab, and ipilimumab is an FDA-approved anti-CTLA-4 agent.1

3d rendered illustration of lung cancer 3D illustration

Image credit: appledesign | stock.adobe.com

Studies investigating the effectiveness of ICIs in patients 70 years and older are crucial out of consideration for immunosenescence. This phenomenon refers to changes in the immune system with age, which could reduce the effectiveness of ICIs in older patients. One such change is the decreased replication of certain immune system cells, including T-cells.1,3

Researchers in Shanghai evaluated 24 phase 3 trials involving ICIs as first- or second-line therapies (as monotherapy or combination therapy). Some trials revealed ICI monotherapy to be more efficacious than chemotherapy for patients 65 and older, the metric of efficacy being overall survival (OS).1

Clinical trials evaluating combination therapy deployed carboplatin, nab-paclitaxel, paclitaxel, and pemetrexed chemotherapeutics with anti-PD-L1 agents. A further trial evaluated nivolumab with ipilimumab, an anti-PD-1 with an anti-CTLA-4 medication (respectively). Like monotherapy, combination therapy also yielded greater OS than chemotherapy alone. However, the increase in OS lessens with age, declining to zero starting at age 75.1

The research team cites factors such as polypharmacy and physiological changes as reasons care teams must practice specificity when tailoring care to older patients. They further point out the problematic nature of this age group’s underrepresentation in clinical trials when planning evidence-based care.1

To guide treatment strategies specific to the older patient with NSCLC—which, in turn, increases the likelihood of tolerance and completion—practitioners should employ specialized geriatric assessment tools. One such comprehensive geriatric assessment (CGA) methodology is the Geriatric-8, which determines an older patient’s risk for certain adverse events.1,4,5

Validated assessment strategies enable practitioners to optimize outcomes by assessing older patients’ fitness for certain therapies. This practice is essential particularly when treating older adults with NSCLC, a patient population lacking statistics to guide treatment due to insufficient representation in clinical trials.1

About the Author

Becca Resnik, RN, is a freelance translator, editor, and writer based in Tennessee.

References

1. Wang L, Zhou J, Yu X, Su C. Immune checkpoint inhibitors in elderly patients with lung cancer: evidence from phase 3 trials. Curr Opin Oncol. 2024;36(1):35-43. doi:10.1097/CCO.0000000000001006

2. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553:446-454. https://doi.org/10.1038/nature25183

3. Lanna A, Henson SM, Escors D, Akbar AN. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells. Nat Immunol. 2014; 15(10):965-972. doi:10.1038/ni.2981

4. Hamaker ME, te Molder M, Thielen N, van Munster BC, Schiphorst AH, van Huis LH. The effect of a geriatric evaluation on treatment decisions and outcome for older cancer patients: a systematic review. J Geriatr Oncol. 2018;9(5):430-440. https://doi.org/10.1016/j.jgo.2018.03.014

5. Gomes F, Lorigan P, Woolley S, et al. A prospective cohort study on the safety of checkpoint inhibitors in older cancer patients — the ELDERS study. ESMO Open. 2021;6(1):100042. https://doi.org/10.1016/j.esmoop.2020.100042

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