Inflammatory indexes neutrophils/lymphocytes, platelets/lymphocytes and red-cell distribution width (RDW) as prognostic biomarkers in advanced solitary fibrous tumors (SFT) treated with pazopanib: Correlative study of GEIS-32 trial.

Authors

Javier Martin Broto

Javier Martin Broto

Virgen del Rocio University Hospital, Institute of Biomedicine Research (IBIS)/CSIC/Universidad de Sevilla, Seville, Spain

Javier Martin Broto , Samuel Hidalgo , David Silva Moura , Silvia Stacchiotti , Antonio Lopez-Pousa , Andrés Redondo , Antoine Italiano , Antonio Gutierrez , Giovanni Grignani , Nadia Hindi , Jose Antonio Lopez-Guerrero , Xavier Garcia del Muro , Javier Martinez-Trufero , Emanuela Palmerini , Ana Sebio , Daniel Bernabeu , Axel Le Cesne , Paolo Giovanni Casali , Jean-Yves Blay , Josefina Cruz Jurado

Organizations

Virgen del Rocio University Hospital, Institute of Biomedicine Research (IBIS)/CSIC/Universidad de Sevilla, Seville, Spain, University Hospital Virgen del Rocio, Sevilla, Spain, Group of Advanced Therapies and Biomarkers in Sarcomas, Institute of Biomedicine of Seville, Ibis/Hospital Universitario Virgen Del Rocío/Csic/Universidad De Sevilla, Seville, Spain, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Hospital Sant Pau, Barcelona, Spain, Hospital Universitario La Paz – IdiPAZ, Madrid, Spain, Early Phase Trials Unit, Institut Bergonié, Bordeaux, France, Hospital Universitario Son Espases, Palma De Mallorca, Spain, Division of Medical Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo (TO), Italy, Istituto Nazionale del Tumori, Milan, Italy, Instituto Valenciano de Oncologia, Valencia, Spain, ICO Hospitalet, Barcelona, Spain, Hospital Universitario Miguel Servet, Zaragoza, Spain, Istituto Ortopedico Rizzoli IRCCS, Bologna, Italy, Hospital de la Santa Creu i Sant Pau, Medical Oncology, Barcelona, Spain, Hospital Universitario La Paz, Madrid, Spain, Institut Gustave Roussy, Villejuif, France, Centre Léon Bérard, Lyon, France, Urbanizacion El Espinal, Tenerife, Spain

Research Funding

No funding received
None

Background: Pazopanib (P) was assessed prospectively in a phase 2 study in SFT resulting in a longer progression free survival (PFS) and overall survival (OS) compared to historical controls treated with chemotherapy. No statistical correlation was found between angiogenic factors and P in its pivotal phase III sarcoma trial. In the last two years, a soaring interest on the prognostic and predictive value of inflammatory indexes such as neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) is emerging in sarcomas. A retrospective analysis of inflammatory indexes of patients who entered the GEIS-32 (NCT02066285) trial was performed. In that trial advanced SFT patients were treated with P from front-line. Methods: All eligible patients who entered in the typical- and malignant-SFT cohort of the GEIS-32 trial were included in this analysis. To determine NLR and PLR, baseline values of platelets (10e9/L), neutrophils (10e9/L) and lymphocytes (10e9/L) were obtained from complete blood count tests. Additionally, RDW (standardized as 1 = upper value of normal range) values at baseline were also determined. The impact of NLR, PLR and RDW on OS, PFS and Choi response were analyzed by univariate and multivariate analysis. MAXSTAT was used to determine optimal cut-off points for overall survival. Metastasis free interval (MFI), mitotic count and ECOG were also analyzed, among others. Results: Sixty-seven out of 70 enrolled SFT patients, median age 63-y and 57% female, were considered for this analysis. The median follow-up from treatment initiation was 20.0 months. High standardized RDW value at baseline (cut-off 1.03) was significantly associated with worse OS [10.7 months (95% CI 3.8-17.5) vs 49.8 months (95% CI 9.4-90.2), p < 0.001] and worse PFS [8.8 months (95% CI 0.9-7.0) vs 9.8 months (7.4-12.3), p = 0.001]. High PLR (cut-off 242) significantly correlated with worse OS [10.7 months (95% CI 5.2-16.2) vs 49.8 months (95% CI 14.6-85.0), p < 0.001] and worse PFS [4.5 months (95% CI 2.0-7.0) vs 10.1 months (95% CI 6.3-13.9), p = 0.005], and high NLR (cut-off 3.78) was significantly associated with worse OS [11.7 months (95% CI 3.5-19.8) vs NA, p < 0.001] and worse PFS [4.5 months (95% CI 1.9-7.0) vs 10.8 months (95% CI 8.7-12.9), p = 0.010]. Independent variables in multivariate analysis were NLR, RDW, MFI and mitosis for PFS; while RDW and ECOG for OS (see table). Further, NLR and mitosis were independent factors for Choi progressive disease (as best response). Conclusions: High NLR and RDW values were independent biomarkers of worse outcome in advanced SFT patients treated with pazopanib.


Factor
HR
95% CIP
PFS
MFI
2.1
1.0-4.1
0.042
NLR
2.8
1.3-5.9
0.008
RDW
2.8
1.3-6.3
0.012
MITOSIS
5.0
2.3-10.4
< 0.001
OS
RDW
7.4
2.4-23.0
0.001
ECOG
8.8
1.9-40.5
0.005

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Clinical Science Symposium

Session Title

Emerging Trends in Sarcoma Precision Medicine

Track

Sarcoma

Sub Track

Molecular Targets/Biomarkers/Tumor Biology

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 11511)

DOI

10.1200/JCO.2021.39.15_suppl.11511

Abstract #

11511

Abstract Disclosures