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
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% CI | P | |
---|---|---|---|---|
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 Disclosures
2019 ASCO Annual Meeting
First Author: Josefina Cruz Jurado
2017 ASCO Annual Meeting
First Author: Javier Martin Broto
2021 ASCO Annual Meeting
First Author: Silvia Stacchiotti
2024 ASCO Genitourinary Cancers Symposium
First Author: Elaine Chang