Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients

Despite increasing clinical interest in adapting checkpoint inhibitor (CPI) therapies for patients with gynecologic malignancies, no accurate clinical biomarkers to predict therapy response and prognosis are currently available. Therefore, we aimed to assess the predictive and prognostic value of pr...

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Autores principales:	Thomas Bartl, Arina Onoprienko, Gerda Hofstetter, Leonhard Müllauer, Nina Poetsch, Thorsten Fuereder, Paul Kofler, Stephan Polterauer, Christoph Grimm
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	immunotherapy immune checkpoint inhibitor biomarker overweight RECIST Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/09f0143a2dda4ef1bc618ca19ad0a7e4
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spelling	oai:doaj.org-article:09f0143a2dda4ef1bc618ca19ad0a7e42021-11-25T16:53:57ZOverweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients10.3390/biom111117002218-273Xhttps://doaj.org/article/09f0143a2dda4ef1bc618ca19ad0a7e42021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1700https://doaj.org/toc/2218-273XDespite increasing clinical interest in adapting checkpoint inhibitor (CPI) therapies for patients with gynecologic malignancies, no accurate clinical biomarkers to predict therapy response and prognosis are currently available. Therefore, we aimed to assess the predictive and prognostic value of pretherapeutic body mass index (BMI) for recurrent gynecologic cancer patients as previously validated for other solid tumors. We evaluated patients with programmed cell death ligand 1 (PD-L1) positive and, in endometrial cancer, also mismatch repair deficient (MMR) gynecologic malignancies, who received the PD-1 inhibitor pembrolizumab as monotherapy (200 mg fixed-dose q3 w) from 2017 to 2020 (n = 48). Thirty-six patients receiving at least four courses were included in the final analysis. Associations between a BMI increase per 5 kg/m<sup>2</sup> and overall response rate (ORR; complete + partial response), disease control rate (DCR; ORR + stable disease), progression-free (PFS), and overall survival (OS) were assessed. An elevated BMI was univariately associated with ORR (OR 10.93 [CI 2.39–49.82], <i>p</i> = 0.002), DCR (OR 2.19 [CI 0.99–4.83], <i>p</i> = 0.048), prolonged PFS (HR 1.54 [CI 1.03–2.34], <i>p</i> = 0.038), and OS (HR 1.87 [CI 1.07–3.29], <i>p</i> = 0.028). All results could be confirmed in the multivariate analyses. Pretherapeutic BMI therefore appears to be a promising readily available biomarker to identify patients with PD-L1-positive and/or MMR-deficient gynecologic malignancies who could particularly benefit from CPI treatment.Thomas BartlArina OnoprienkoGerda HofstetterLeonhard MüllauerNina PoetschThorsten FuerederPaul KoflerStephan PolterauerChristoph GrimmMDPI AGarticleimmunotherapyimmune checkpoint inhibitorbiomarkeroverweightRECISTMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1700, p 1700 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunotherapy immune checkpoint inhibitor biomarker overweight RECIST Microbiology QR1-502
spellingShingle	immunotherapy immune checkpoint inhibitor biomarker overweight RECIST Microbiology QR1-502 Thomas Bartl Arina Onoprienko Gerda Hofstetter Leonhard Müllauer Nina Poetsch Thorsten Fuereder Paul Kofler Stephan Polterauer Christoph Grimm Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients
description	Despite increasing clinical interest in adapting checkpoint inhibitor (CPI) therapies for patients with gynecologic malignancies, no accurate clinical biomarkers to predict therapy response and prognosis are currently available. Therefore, we aimed to assess the predictive and prognostic value of pretherapeutic body mass index (BMI) for recurrent gynecologic cancer patients as previously validated for other solid tumors. We evaluated patients with programmed cell death ligand 1 (PD-L1) positive and, in endometrial cancer, also mismatch repair deficient (MMR) gynecologic malignancies, who received the PD-1 inhibitor pembrolizumab as monotherapy (200 mg fixed-dose q3 w) from 2017 to 2020 (n = 48). Thirty-six patients receiving at least four courses were included in the final analysis. Associations between a BMI increase per 5 kg/m<sup>2</sup> and overall response rate (ORR; complete + partial response), disease control rate (DCR; ORR + stable disease), progression-free (PFS), and overall survival (OS) were assessed. An elevated BMI was univariately associated with ORR (OR 10.93 [CI 2.39–49.82], <i>p</i> = 0.002), DCR (OR 2.19 [CI 0.99–4.83], <i>p</i> = 0.048), prolonged PFS (HR 1.54 [CI 1.03–2.34], <i>p</i> = 0.038), and OS (HR 1.87 [CI 1.07–3.29], <i>p</i> = 0.028). All results could be confirmed in the multivariate analyses. Pretherapeutic BMI therefore appears to be a promising readily available biomarker to identify patients with PD-L1-positive and/or MMR-deficient gynecologic malignancies who could particularly benefit from CPI treatment.
format	article
author	Thomas Bartl Arina Onoprienko Gerda Hofstetter Leonhard Müllauer Nina Poetsch Thorsten Fuereder Paul Kofler Stephan Polterauer Christoph Grimm
author_facet	Thomas Bartl Arina Onoprienko Gerda Hofstetter Leonhard Müllauer Nina Poetsch Thorsten Fuereder Paul Kofler Stephan Polterauer Christoph Grimm
author_sort	Thomas Bartl
title	Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients
title_short	Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients
title_full	Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients
title_fullStr	Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients
title_full_unstemmed	Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients
title_sort	overweight as a favorable clinical biomarker for checkpoint inhibitor therapy response in recurrent gynecologic cancer patients
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/09f0143a2dda4ef1bc618ca19ad0a7e4
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Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients

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