Decline in Smartphone-Assessed Physical Activity Level is Associated With Clinical Outcomes in Phase I/II Clinical Cancer Trials

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Calvin G. Brouwer Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands

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Joeri A.J. Douma Department of Medical Oncology, Medical Centre Leeuwarden, Leeuwarden, the Netherlands

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Evelien J.M. Kuip Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands
Department of Anesthesiology, Pain, and Palliative Care, Radboud University Medical Center, Nijmegen, the Netherlands

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Sonja Zweegman Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, the Netherlands

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Niels W.C.J van de Donk Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, the Netherlands

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Maria T.E. Hopman Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands

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Myra E. van Linde Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, the Netherlands

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Henk M.W. Verheul Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus Medical Center, Erasmus University, Rotterdam, the Netherlands

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Laurien M. Buffart Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands

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Background: A decline in physical function may be an early predictor for complications of cancer treatment. This study examined whether repeated objective smartphone measurements of physical activity and exercise capacity in patients with cancer are feasible during early-phase clinical trials (EPCTs) and whether a decline in physical function is associated with clinical outcomes. Methods: Physical activity (steps/day) and exercise capacity (6-minute walk test [6MWT]) were measured with a smartphone before EPCT start (T0) and after 4 weeks (T1) and 8 weeks (T2). Univariable logistic regression analyzed associations between a decline in step count (≥20%), 6MWT distance (≥10%), or deterioration of ECOG performance status (PS) and trial discontinuation at 8 weeks and 90 days. Cox proportional hazards models were used to examine associations with progression-free survival (PFS) and overall survival (OS), adjusting for trial phase (I vs II), cancer type (hematologic malignancy vs solid tumor), and PS (0 vs ≥1). Results: Among 117 included patients, valid step count and 6MWT measurements were available for 96.6% and 76.7% of patients at T0, 74.4% and 53.3% at T1, and 89.7% and 54.4% at T2, respectively. Patients experiencing step count decline between T0 and T1 had higher odds of trial discontinuation at 8 weeks (odds ratio, 8.67; 95% CI, 1.94–61.43), and decline between T1 and T2 was associated with discontinuation at 90 days (odds ratio, 5.20; 95% CI, 1.43–21.14). Step count decline was significantly associated with shorter PFS (hazard ratio, 3.54; 95% CI, 2.06–6.08) and OS (hazard ratio, 2.31; 95% CI, 1.26–4.23). Declines in 6MWT distance or deterioration in ECOG PS were not associated with trial discontinuation or survival. Conclusions: Repeated smartphone measurements of physical activity are feasible in patients participating in EPCTs. Additionally, physical activity decline is significantly associated with trial discontinuation, PFS, and OS. Hence, we envision that objective smartphone measurements of physical activity will contribute to optimal treatment development for patients with cancer.

Submitted October 7, 2023; final revision received December 21, 2023; accepted for publication January 4, 2024. Published online May 22, 2024.

H.M.W. Verheul and L.M. Buffart contributed equally to this study.

Author contributions: Conceptualization: Douma, Verheul, Buffart. Data curation: Brouwer, Douma. Formal analysis: Brouwer, Buffart. Investigation: Zweegman, van de Donk, van Linde. Methodology: Douma, Verheul, Buffart. Resources: Zweegman, van de Donk, van Linde. Supervision: Kuip, Hopman, Verheul, Buffart. Writing—original draft: Brouwer, Douma, Verheul, Buffart. Writing—review & editing: All authors.

Disclosures: Dr. van de Donk has disclosed receiving grant/research support from Janssen Pharmaceuticals, Amgen, Celgene Corporation, Novartis, Cellectis, and Bristol Myers Squibb; and serving as a scientific advisor for Janssen Pharmaceuticals, Amgen, Celgene Corporation, Bristol Myers Squibb, Takeda Pharmaceuticals, Roche, Novartis, Bayer, Adaptive Biotechnologies, Pfizer, AbbVie, and Servier. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Laurien M. Buffart, PhD, Department of Medical BioSciences (HP 928), Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands. Email: laurien.buffart@radboudumc.nl
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