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Randomized Controlled Trial
. 2024 Oct;9(10):103738.
doi: 10.1016/j.esmoop.2024.103738. Epub 2024 Oct 10.

Leptin as a surrogate immune-metabolic marker to predict impact of anti-cachectic therapy: results of a prospective randomized trial in multiple solid tumors

C Madeddu  1 , G Gramignano  2 , E Lai  3 , G Pinna  3 , L Tanca  4 , M C Cherchi  4 , C Floris  5 , D Farci  5 , A Pretta  3 , M Scartozzi  3 , A Macciò  6
Affiliations
Randomized Controlled Trial

Leptin as a surrogate immune-metabolic marker to predict impact of anti-cachectic therapy: results of a prospective randomized trial in multiple solid tumors

C Madeddu et al. ESMO Open. 2024 Oct.

Abstract

Description of the work: Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia.

Purpose: To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment.

Patients and methods: From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus l-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life.

Results: A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue.

Conclusions: Leptin is a reliable predictive marker for multitargeted anti-cachectic treatment outcomes. Thus, it can be an ideal candidate for monitoring and predicting the effects of anti-cachectic treatment and a surrogate marker of the immune-metabolic actions of the selected drugs.

Keywords: cachexia; combined approach; inflammation; leptin; quality of life; sarcopenia.

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Figures

Figure 1
Figure 1
ROC and AUC of baseline leptin for cachexia severity (left side) and sarcopenia (right side) in the exploratory (A) and validation (B) cohort. AUC, area under the curve; ROC, receiver operating curve.
See this image and copyright information in PMC

References

    1. Argilés J.M., López-Soriano F.J., Stemmler B., Busquets S. Cancer-associated cachexia – understanding the tumour macroenvironment and microenvironment to improve management. Nat Rev Clin Oncol. 2023;20(4):250–264. - PubMed
    1. Fearon K., Strasser F., Anker S.D., et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–495. - PubMed
    1. Ferrer M., Anthony T.G., Ayres J.S., et al. Cachexia: a systemic consequence of progressive, unresolved disease. Cell. 2023;186(9):1824–1845. - PMC - PubMed
    1. Maccio A., Sanna E., Neri M., Oppi S., Madeddu C. Cachexia as evidence of the mechanisms of resistance and tolerance during the evolution of cancer disease. Int J Mol Sci. 2021;22(6):2890. - PMC - PubMed
    1. Macciò A., Lai P., Santona M.C., Pagliara L., Melis G.B., Mantovani G. High serum levels of soluble IL-2 receptor, cytokines, and C reactive protein correlate with impairment of T cell response in patients with advanced epithelial ovarian cancer. Gynecol Oncol. 1998;69(3):248–252. - PubMed

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