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. 2025 Aug 4;30(8):oyae349.
doi: 10.1093/oncolo/oyae349.

Associations of frailty with survival, hospitalization, functional decline, and toxicity among older adults with advanced non-small cell lung cancer

Howard J Lee Jr  1 , John Boscardin  2 , Louise C Walter  2 , Alexander K Smith  2 , Harvey J Cohen  3 , Smith Giri  4 , Grant R Williams  4 , Carolyn J Presley  5 , Surbhi Singhal  6 , Li-Wen Huang  1   7 , Ana I Velazquez  1   8 , Matthew A Gubens  1   8 , Collin M Blakely  1   8 , Claire K Mulvey  1   8 , Michael L Cheng  1   8 , Lori C Sakoda  9   10 , Lawrence H Kushi  9 , Charles Quesenberry  9 , Raymond Liu  9   11 , Sara Fleszar-Pavlovic  12 , Caroline Eskandar  2 , Edward Cutler  13 , Anne Marie Mercurio  13 , Melisa L Wong  2   9   11
Affiliations

Associations of frailty with survival, hospitalization, functional decline, and toxicity among older adults with advanced non-small cell lung cancer

Howard J Lee Jr et al. Oncologist. .

Abstract

Introduction: Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy.

Methods: Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months. We developed a deficit-accumulation frailty index to categorize patients as robust, pre-frail, or frail. To evaluate associations between frailty and KPS with OS, we used Cox proportional hazards models adjusted for race, insurance, and treatment. We used logistic regression to evaluate hospitalizations, functional decline, and severe toxicity.

Results: Among 155 patients (median age 73), 45.8% were robust, 36.1% pre-frail, and 18.2% frail; 34.8% had a KPS ≥ 90, 32.9% had a KPS of 80, and 32.3% had a KPS ≤ 70. The median OS was 17.9 months. Pre-frail/frail patients had worse OS compared to robust patients (adjusted hazard ratio [HR] 2.09, 95% CI, 1.31-3.34) and were more likely to be hospitalized (adjusted odds ratio [OR] 2.21, 95% CI, 1.09-4.48), functionally decline (adjusted OR 2.29, 95% CI, 1.09-4.78), and experience grade ≥ 3 hematologic toxicity (adjusted OR 5.18, 95% CI, 1.02-26.03). KPS was only associated with OS.

Conclusions: Our frailty index was associated with OS, hospitalization, functional decline, and hematologic AEs among older adults with aNSCLC receiving systemic therapies, while KPS was only associated with OS. Pretreatment frailty assessment may help identify older adults at risk for poor outcomes to optimize decision-making and supportive care.

Keywords: frailty index; geriatric assessment; lung cancer; older; performance status.

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Conflict of interest statement

The following authors reported conflicts of interest outside the submitted work:

S.G.—research funding and honoria from Janssen and Sanofi.

G.R.W.—consultant/advisor to Cardinal Health, Bayer, and Takeda.

C.J.P.—research funding from BMS Foundation and Rising Tide Foundation awarded directly to her institution; consultant/advisor to Jazz Pharmaceuticals and Regeneron.

S.S.—consultant/advisor to OncoHost.

A.I.V.—research funding from the National Institute on Aging, AACR, Conquer Cancer, and Lungevity; consultant/advisor to Merus, AstraZeneca, and Novocure; honoraria from BioAscend, ASCO, OptumHealth Education, MJH Life Sciences, MDOutlook, Curio Science, ObR Oncology, and CMEOutfitters; and travel, accommodations, expenses from DAVAOncology and BioAscend.

M.A.G.—research funding from Amgen, Johnson & Johnson, Merck, and Trizell awarded directly to his institution; consultant/advisor to AnHeart, AstraZaneca, Atreca, BMS, Cardinal Health, Genentech/Roche, Genzyme, Gilead, Guardant, Invitae, iTeos, Merus, Sanofi, Summit, and Surface.

C.M.B.—research funding from AstraZeneca, Novartis, Puma, and Mirati awarded directly to his institution; consultant/advisor to BMS, Gilead, and Bayer.

M.L.C.—honoraria from Lynx Group, WebMD, and Potomac Center for Medical Education; consultant/advisor to AstraZeneca, Boehringer Ingelheim, Mirati Therapeutics, Cepheid, Janssen, and Pfizer; research funding from Palleon Pharmaceuticals (Inst); and travel, accommodations, expenses from Daiichi Sankyo, AstraZeneca, and Genzyme.

L.C.S.—research funding from AstraZeneca, National Cancer Institute, and California Tobacco-Related Disease Research Program awarded directly to her institution; unpaid leadership role within the American Cancer Society (National Lung Cancer Roundtable Health Equity Task Group co-chair); stock ownership for Johnson & Johnson; and travel, accommodations, expenses from the American Cancer Society.

R.L.—research funding from AstraZeneca awarded directly to his institution.

C.E.—stock ownership for Johnson & Johnson, Pfizer, Moderna, Mural Oncology Public Limited, Walgreens Boots Alliance, Acadia Healthcare Co, and Bean Therapeutics.

M.L.W.—royalties from UpToDate; immediate family member is an employee of Genentech with stock ownership.

The remaining authors have no conflicts to report.

Figures

Figure 1.
Figure 1.
Distribution of deficit-accumulation frailty index scores among adults aged ≥ 65 with advanced non-small cell lung cancer starting a new chemotherapy, immunotherapy, and/or targeted therapy regimen for non-curative intent.
Figure 2.
Figure 2.
Distribution of deficit-accumulation frailty index scores among older adults with advanced non-small cell lung cancer with a Karnofsky Performance Status (KPS) (A) ≥ 90, (B) KPS 80, and (C) KPS ≤ 70.
Figure 3.
Figure 3.
Kaplan–Meier analysis of OS among older adults with advanced non-small cell lung cancer according to deficit-accumulation frailty index category
Figure 4.
Figure 4.
Kaplan–Meier analysis of OS among older adults with advanced non-small cell lung cancer according to Karnofsky Performance Status (KPS).
See this image and copyright information in PMC

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