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Cited by 100Cancer Immunotherapy and BiomarkersLung Cancer Treatments and MutationsLung Cancer Diagnosis and Treatment

FDA analyses of survival in older adults with metastatic non–small cell lung cancer in controlled trials of PD-1/PD-L1 blocking antibodies

Marur, Shanthi, Singh, Harpreet, Mishra-Kalyani, Pallavi, Larkins, Erin, Keegan, Patricia, Sridhara, Rajeshwari, Blumenthal, Gideon M., Pazdur, Richard·2018·Seminars in Oncology
DOI 10.1053/j.seminoncol.2018.08.007
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Abstract

Background Among patients with newly diagnosed non-small cell lung cancer (NSCLC), approximately 70% occur in those above 65 years of age and more than half are metastatic or locally advanced NSCLC.Methods Retrospective analyses pooling data across 4 randomized clinical trials comparing programmed death 1 receptor (PD-1) or programmed death ligand 1 (PD-L1) to docetaxel for the treatment of patients with advanced or metastatic NSCLC with disease progression on or after a platinum-containing therapy were conducted. Demographics, efficacy, and safety data from these trials were pooled and aggregated based on age. The relative treatment effects on overall survival (OS) across age groups were evaluated using Kaplan-Meier methodology. A meta-analysis was performed comparing OS across age groups treated with PD-1/PD-L1 blocking antibodies compared with those treated with docetaxel, as a common control arm across trials. A Cox Proportional Hazards model, stratified by clinical trial, was used and a univariate and multivariate adjusted analysis of OS to further identify trends in efficacy across age groups.Results Among patients treated with PD-1/PD-L1 blocking antibodies enrolled across the 4 clinical trials, 42% were >65 years of age, 99% had ECOG performance status of 0-1, 75% had received 1 prior therapy, and 76% were diagnosed with Stage IV disease. In the pooled analysis of 2,824 patients across both arms, the treatment effects in age-defined subgroups were similar, with a hazard ratios (HR), unadjusted or adjusted, for OS of 0.71 (95% confidence interval 0.63, 0.80) in patients <65 years and 0.66 (0.57, 0.76) in patients ≥65 years of age. In patients ≥70 years, the HR for OS was 0.67 (0.55. 0.82) and in patients ≥ 75 years, the HR was 0.81 (0.58, 1.13). Estimated median OS in patients receiving PD-1/PD-L1 blocking antibodies versus docetaxel was 14.5 months versus 8.8 months in patients <65 years, 14.2 months versus 9 months in patients ≥65 years, 14.1 versus 9.2 months in patients ≥70 years, and 14.7 versus 9.5 months in the patients ≥75years. Grade 3 or 4 treatment-related adverse events with PD-1/PD-L1 blocking antibodies were less frequent in patients ≥75 years (23%) compared to patients> 65 year ( 49%) and <65 years (47%), as were serious adverse events (30%, 32.5%, 15%); however, treatment-emergent adverse events leading to discontinuation of treatment (7%, 7%, and 5%) in those subgroups ≤65 years, >65 years, and >75 years, respectively, were similar.Conclusions Patients 65 and older with advanced and metastatic NSCLC, including those ≥75 years, seem to derive similar survival benefits from treatment with PD-1/PD-L1 blocking antibodies as patients <65 years of age. Patients 75 and older enrolled on these trials appear to tolerate PD-1/PD-L1 blocking antibodies and have a lower incidence of grade 3 or 4 treatment-emergent adverse events compared to the subgroup of patients <65 years of age.

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Crossref · 10.1053/j.seminoncol.2018.08.007

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  • Anti-PD-1 drugs are effective for both young and elderly patients.

    “A meta-analysis of randomized trials showed that although anti-PD-1 drugs are effective for both young and elderly patients, the risk of death among elderly patients is comparable or improved compared to that of patients subjected to control interventions, with no increased toxicity [155–158].”

    From Immunosenescence: a key player in cancer development (2020) · cites this paper as [157]

  • Anti-PD-1 drugs cause no increased toxicity in elderly patients.

    “with no increased toxicity [155–158].”

    From Immunosenescence: a key player in cancer development (2020) · cites this paper as [157]

  • The risk of death among elderly patients receiving anti-PD-1 drugs is comparable or improved compared to control interventions.

    “the risk of death among elderly patients is comparable or improved compared to that of patients subjected to control interventions, with no increased toxicity [155–158].”

    From Immunosenescence: a key player in cancer development (2020) · cites this paper as [157]

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Authors
Marur, S., Singh, H., Mishra-Kalyani, P., Larkins, E., Keegan, P., Sridhara, R., Blumenthal, G. M., & Pazdur, R.
Affiliations
United States Food and Drug Administration (US)
Corresponding author
Singh, Harpreet
ORCID
Venue
Seminars in Oncology
Publisher
Elsevier BV
Published
2018-08
Volume
45
Issue
4
Pages
220-225
ISSN
0093-7754 (ISSN-L)
DOI
10.1053/j.seminoncol.2018.08.007
OpenAlex
W2899413762
Cited by
100
References
7
Citations by year
2026: 4 · 2025: 7 · 2024: 8 · 2023: 19 · 2022: 13 · 2021: 19 · 2020: 21 · 2019: 9
FWCI
4.60
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Seminars in Oncology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords
metastatic non-small cell lung cancer, older adults, overall survival, docetaxel, age subgroup analysis, treatment efficacy, immune checkpoint inhibitors, platinum-refractory disease, ECOG performance status, treatment safety, adverse events, randomized controlled trials, pooled analysis, meta-analysis, Cox proportional hazards model
MeSH terms
Antineoplastic Agents, Immunological, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunotherapy, Lung Neoplasms, Male, United States, United States Food and Drug Administration, Randomized Controlled Trials as Topic, Antibodies, Blocking, B7-H1 Antigen, Programmed Cell Death 1 Receptor

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