“The advent of immunotherapy, particularly the checkpoint inhibitors that target PD-1 and PD-L1, have provided more therapy options for our older adults with advanced NSCLC in the first-line and second-line arenas,” said Ronald Maggiore, MD, assistant professor of medicine at the University of Rochester Medical Center and Wilmot Cancer Institute in New York.
“These agents as monotherapy have been well tolerated in clinical practice, and generally better tolerated than cytotoxic chemotherapy, in adults aged 70 years or older,” Dr Maggiore told Cancer Therapy Advisor.
Even though immunotherapy-associated immune-related adverse events (irAEs) are rare — occurring in perhaps 10% of patients undergoing immune checkpoint inhibition monotherapy — their overall safety profiles for elderly patients — particularly when combined with other treatment modalities — are still not yet completely understood. Yet when irAEs do occur, they can be life-threatening, particularly if they are not quickly detected and treated.7
Like age-related functional declines in other organ systems, the aging immune system’s vigilance against infections and cancer cells wanes. Immunosenescence affects both the innate and the adaptive immune systems, including T cell lymphocyte function. Aging is associated with increased levels of inflammatory cytokines and upregulated cell surface expression of PD-1 receptors — leading authors of a recent review of immunotherapy in treating elderly patients with advanced lung cancer to conclude that immunosenescence might well affect the efficacy and toxicity of immune checkpoint blockade, although more clinical research is needed for confirmation.1
Participants in the clinical trials on which basis the U.S. Food and Drug Administration (FDA) approved these agents were also more fit, younger, and had fewer comorbidities than those seen in the elderly lung cancer patient population. No randomized, phase 3 clinical trials of PD1/PD-L1 immunotherapies have been conducted specifically among elderly patients with advanced NSCLC.
“Real-world evidence on how immunotherapy and targeted treatments are tolerated in older adults with multiple chronic conditions, polypharmacy, and geriatric syndromes is lacking,” Dr Presley noted. “Clinical trial evidence is not easily extrapolated to the general elderly population as only the healthiest older adults are included on clinical trials.”
An analysis of FDA data presented at the American Society of Clinical Oncology (ASCO) 2016 annual meeting indicated that among older adults administered immune checkpoint inhibitors for advanced cancers, “there may be a higher need for immunomodulatory therapy to manage clinically significant immune-related adverse events despite the overall low incidence of toxicity.”8
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As more and more patients with lung cancer and other malignancies are diagnosed during late adulthood, enrolling elderly participants in clinical trials is becoming more of a priority. Relaxing age-related eligibility criteria for cancer immunotherapy clinical trials to allow higher numbers of elderly patients to participate in research and would hasten improvements in the understanding of treatment efficacy and safety in older patients.
- Sgambato A, Casaluce F, Gridelli C. The role of checkpoint inhibitors immunotherapy in advanced non-small cell lung cancer in the elderly. Expert Opin Biol Ther. 2017 Feb 20. doi: 10.1080/14712598.2017.1294157 [Epub ahead of print]
- Gajra A, Akbar SA, Din NU. Management of lung cancer in the elderly. Clin Geriatr Med. 2016;32:81-95. doi: 10.1016/j.cger.2015.08.008
- Schulkes KJ, Hamaker ME, van den Bos F, van Elden LJ. Relevance of a geriatric assessment for elderly patients with lung cancer-a systematic review. Clin Lung Cancer. 2016;17(5):341-9. doi: 10.1016/j.cllc.2016.05.007
- Kanesvaran R, Chowdhury AR, Krishna L. Practice pearls in the management of lung cancer in the elderly. J Geriatr Oncol. 2016;7:362-7. doi: 10.1016/j.jgo.2016.05.004
- Zaki M, Dominello M, Dyson G, et al. Outcomes of elderly patients who receive combined modality therapy for locally advanced non-small-cell lung cancer. Clin Lung Cancer. 2016;18(1):e21-e26. doi: 10.1016/j.cllc.2016.07.005
- Nishijima TF, Muss HB, Shachar SS, Moschos SJ. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta-analysis. Cancer Treat Rev. 2016;45:30-7. doi: 10.1016/j.ctrv.2016.02.006
- Helissey C, Vicier C, Champiat S. The development of immunotherapy in older adults: new treatments, new toxicities? J Geriatr Oncol. 2016;7:325-33. doi: 10.1016/j.jgo.2016.05.007
- Singh H. FDA subset analysis of the safety of nivolumab in elderly patients with advanced cancers. ASCO website. http://meetinglibrary.asco.org/content/123271?media=vm. Accessed March, 2017.