Mortality burden of pre‐treatment weight loss in patients with non‐small‐cell lung cancer: A systematic literature review and meta‐analysis

Author:

Bonomi Philip D.1ORCID,Crawford Jeffrey2,Dunne Richard F.3,Roeland Eric J.4,Smoyer Karen E.5,Siddiqui Mohd Kashif6,McRae Thomas D.7,Rossulek Michelle I.8,Revkin James H.9,Tarasenko Lisa C.10

Affiliation:

1. Department of Internal Medicine, Division of Hematology, Oncology and Cell Therapy Rush University Medical Center Chicago IL USA

2. Duke Cancer Institute Duke University Medical Center Durham NC USA

3. Department of Medicine and Wilmot Cancer Institute, Division of Hematology/Oncology University of Rochester Medical Center Rochester NY USA

4. Knight Cancer Institute Oregon Health and Science University Portland OR USA

5. Curo Envision Pharma Group Philadelphia PA USA

6. EBM Health Consultants New Delhi Delhi India

7. Internal Medicine Business Unit, Global Product Development Pfizer Inc New York NY USA

8. Internal Medicine Research Unit, Worldwide Research, Development and Medical Pfizer Inc Cambridge MA USA

9. Internal Medicine Research Unit, Clinical Development Pfizer Inc Cambridge MA USA

10. Global Medical Affairs Pfizer Inc New York NY USA

Abstract

AbstractCachexia, with weight loss (WL) as a major component, is highly prevalent in patients with cancer and indicates a poor prognosis. The primary objective of this study was to conduct a meta‐analysis to estimate the risk of mortality associated with cachexia (using established WL criteria prior to treatment initiation) in patients with non‐small‐cell lung cancer (NSCLC) in studies identified through a systematic literature review. The review was conducted according to PRISMA guidelines. Embase® and PubMed were searched to identify articles on survival outcomes in adult patients with NSCLC (any stage) and cachexia published in English between 1 January 2016 and 10 October 2021. Two independent reviewers screened titles, abstracts and full texts of identified records against predefined inclusion/exclusion criteria. Following a feasibility assessment, a meta‐analysis evaluating the impact of cachexia, defined per the international consensus criteria (ICC), or of pre‐treatment WL ≥ 5% without a specified time interval, on overall survival in patients with NSCLC was conducted using a random‐effects model that included the identified studies as the base case. The impact of heterogeneity was evaluated through sensitivity and subgroup analyses. The standard measures of statistical heterogeneity were calculated. Of the 40 NSCLC publications identified in the review, 20 studies that used the ICC for cachexia or reported WL ≥ 5% and that performed multivariate analyses with hazard ratios (HRs) or Kaplan–Meier curves were included in the feasibility assessment. Of these, 16 studies (80%; n = 6225 patients; published 2016–2021) met the criteria for inclusion in the meta‐analysis: 11 studies (69%) used the ICC and 5 studies (31%) used WL ≥ 5%. Combined criteria (ICC plus WL ≥ 5%) were associated with an 82% higher mortality risk versus no cachexia or WL < 5% (pooled HR [95% confidence interval, CI]: 1.82 [1.47, 2.25]). Although statistical heterogeneity was high (I2 = 88%), individual study HRs were directionally aligned with the pooled estimate, and there was considerable overlap in CIs across included studies. A subgroup analysis of studies using the ICC (HR [95% CI]: 2.26 [1.80, 2.83]) or WL ≥ 5% (HR [95% CI]: 1.28 [1.12, 1.46]) showed consistent findings. Assessments of methodological, clinical and statistical heterogeneity indicated that the meta‐analysis was robust. Overall, this analysis found that ICC‐defined cachexia or WL ≥ 5% was associated with inferior survival in patients with NSCLC. Routine assessment of both weight and weight changes in the oncology clinic may help identify patients with NSCLC at risk for worse survival, better inform clinical decision‐making and assess eligibility for cachexia clinical trials.

Funder

Pfizer

Publisher

Wiley

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