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. 2024 Jun:204:114048.
doi: 10.1016/j.ejca.2024.114048. Epub 2024 Apr 8.

Validation of the Lung Immune Prognostic Index (LIPI) as a prognostic biomarker in metastatic renal cell carcinoma

Lucia Carril-Ajuria  1 , Pernelle Lavaud  2 , Cecile Dalban  3 , Sylvie Negrier  4 , Gwénaëlle Gravis  5 , Robert J Motzer  6 , Christine Chevreau  7 , Nizar M Tannir  8 , Stéphane Oudard  9 , David F McDermott  10 , Brigitte Laguerre  11 , Hans J Hammers  12 , Philippe Barthelemy  13 , Elizabeth R Plimack  14 , Delphine Borchiellini  15 , Marine Gross-Goupil  16 , Ruiyun Jiang  17 , Chung-Wei Lee  17 , Heshani de Silva  17 , Brian I Rini  18 , Bernard Escudier  2 , Laurence Albigès  19
Affiliations

Validation of the Lung Immune Prognostic Index (LIPI) as a prognostic biomarker in metastatic renal cell carcinoma

Lucia Carril-Ajuria et al. Eur J Cancer. 2024 Jun.

Abstract

Background: The Lung Immune Prognostic Index (LIPI) is associated with immune checkpoint inhibitors (ICI) outcomes across different solid tumors, particularly in non-small cell lung cancer. Data regarding the prognostic and/or predictive role of LIPI in metastatic renal cell carcinoma (mRCC) are still scarce. The aim of this study was to evaluate whether LIPI could be predictive of survival in mRCC patients.

Methods: We used patient level data from three different prospective studies (NIVOREN trial: nivolumab; TORAVA trial: VEGF/VEGFR-targeted therapy (TT); CheckMate 214: nivolumab-ipilimumab vs sunitinib). LIPI was calculated based on a derived neutrophils/(leukocyte-neutrophil) ratio > 3 and lactate-dehydrogenase >upper limit of normal, classifying patients into three groups (LIPI good, 0 factors;LIPI intermediate (int), 1 factor;LIPI poor, 2 factors) and/or into two groups (LIPI good, 0 factors;LIPI int/poor, 1-2 factors) according to trial sample size. Primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS).

Results: In the Nivolumab dataset (n = 619), LIPI was significantly associated with OS (LIPI-good 30.1 vs 13.8 months in the LIPI int/poor; HR= 0.47) and PFS (HR=0.74). In the VEGF/VEGFR-TT dataset (n = 159), only a correlation with PFS was observed. In the CheckMate214 dataset (n = 1084), LIPI was significantly associated with OS (nivolumab-ipilimumab OS LIPI good vs int/poor: HR=0.55, p < 0.0001; sunitinib: OS LIPI good vs int/poor: 0.38, p < 0.0001) in both treatment groups in univariate and multivariate analysis.

Conclusions: Pretreatment-LIPI correlated with worse survival outcomes in mRCC treated with either ICI or antiangiogenic therapy, confirming LIPI's prognostic role in mRCC irrespective of systemic treatment used.

Keywords: Antiangiogenics; Biomarkers; LIPI; Prognosis; Renal cell carcinoma; immune checkpoint inhibitors.

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Conflict of interest statement

Declaration of Competing Interest LCA: Travel/accomodation: Pfizer, Ipsen. Honoraria: Ipsen, Janssen. PL: Travel accomodation: IPSEN, JANSSEN, Astellas, Pfizer, Chugai, Sanofi. Consulting/Advisory: Astellas, AZ, Sanofi, BMS. Grant: Servier. SN Honoraria: Pfizer, Ipsen, Merck Sharp & Dohme, Bristol-Myers Squibb, Eisai. Travel/accomodation: Pfizer, Ipsen, Merck Sharp & Dohme, Bristol-Myers Squibb. Research funding: Ipsen, Pfizer and Merck Sharp & Dohme. GG: Travel, Accommodations, Expenses: Janssen Oncology, Bristol-Myers Squibb, Astellas Pharma, Pfizer, Ipsen. RJM: Research funding from Bristol Myers Squibb, Eisai, Exelixis, Genentech/Roche, Merck, Pfizer, and Aveo Pharmaceuticals; consulting fees from AstraZeneca, Aveo Pharmaceuticals, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly, Merck, Novartis, Pfizer, and Takeda. CC: Consulting or Advisory Role: Bristol-Myers Squibb, Novartis, Ipsen, Pfizer. Travel, Accommodations, Expenses: Pfizer, Ipsen, AstraZeneca, Bristol-Myers Squibb, MSD Oncology. NT: Honorarium: AstraZeneca, Bristol-Myers-Squibb, Eisai Medical Research, Exelixis, lntellisphere, Merck Sharp & Dohme, Nektar Therapeutics, Neoleukin, Oncorena. Clinical Grants: Arrowhead Pharmaceuticals, Institutional Bristol-Myers-Squibb, Institutional Calithera Biosciences, Institutional Exelixis, Institutional Nektar Therapeutics, Institutional Novartis, Institutional. SO: Honoraria/advisory board: Astellas, Bayer, BSM, Eisai, Ipsen, Janssen, Merck, Novartis, Pfizer, Sanofi. travel support: Astellas, Bayer, BSM, Eisai, Ipsen, Janssen, Merck, Novartis, Pfizer, Sanofi. Grants: Astellas, Bayer, BSM, Ipsen, Janssen, Novartis, Pfizer, Sanofi. DFM: reported honoraria from BMS, Pfizer, Merck, Alkernes, EMD Serono, Eli Lilly and Company, Iovance, Eisai, Werewolf Therapeutics, Calithera Biosciences, and research funding from BMS, Merck, Genentech, Pfizer, Exelixis, X4 Pharma, and Alkermes. BL: Honoraria: Sanofi, Bristol-Myers Squibb, Roche. Travel, Accommodations, Expenses: Pfizer, Bristol-Myers Squibb, Janssen Oncology. HH: reported receiving grants from Bristol Myers Squibb outside the submitted work. PB: Member of the advisory board of Bristol Myers Squibb, Pfizer, Merck, IPSEN, AMGEN, AstraZeneca, Janssen-Cilag, Astellas, Bayer, MSD, Advanced Accelerator Applications (AAA), and GILEAD. EP: has received research funding from Astellas Pharma US, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Genentech, Infinity Pharmaceuticals, Merck & Co., Peloton Therapeutics, and Pfizer, and serves as a consultant for Bristol-Myers Squibb, Flatiron Health, Genentech, Merck & Co., and Seattle Genetics. DP: Consulting or Advisory Role: Astellas Pharma, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, Novartis, Pfizer, Sanofi, Roche, MSD Oncology, AstraZeneca. Research Funding: Astellas Pharma (Inst), Janssen-Cilag (Inst), MSD Oncology (Inst), AstraZeneca/MedImmune (Inst), Genentech (Inst), Pfizer (Inst). MGG: honoraria for consultancy/ advisory board: BMS, MSD, Ipsen, Pfizer, Eisai, astra Zeneca. Travel support: MSD, Ipsen. BR: serves as a consultant for and has received research funding from Pfizer, Merck, GNE/Roche, Peloton, Aveo, and BMS; has received research funding from AstraZeneca; serves as a consultant for Novartis, Synthorx, Compugen, Corvus, and Exelixis; and owns stock in PTC Therapeutics. BE: Honoraria: Pfizer, BMS, Travel: BMS, Ipsen, MSD. LA: Honoraria: Astellas Pharma, Eisai, Ipsen, F. Homann-La Roche, BMS, Janssen Pharmaceuticals, Merck Sharp and Dohme. Travel: Merck Sharp and Dohme, BMS. CD, RJ, CWL and HDS have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Overall survival (OS) and Progression-free survival (PFS) according to the LIPI groups (intermediate/poor versus good) in the Nivolumab and VEGF/VEGFR TT datasets. (A) OS according to the two LIPI groups in mRCC treated with nivolumab within the NIVOREN trial (Nivolumab dataset). (B) PFS according to two LIPI groups in mRCC treated with nivolumab within the NIVOREN trial (Nivolumab dataset). (C) OS according to the two LIPI groups in mRCC treated with antiangiogenics within the TORAVA trial (VEGF/VEGFR TT dataset). (D) PFS according to the two LIPI groups in mRCC treated with antiangiogenics within the TORAVA trial (VEGF/VEGFR TT dataset).
Figure 2.
Figure 2.
Overall survival (OS) and Progression-free survival (PFS) according to the LIPI groups (intermediate/poor versus good) in the Checkmate 214 trial. (A) OS by LIPI group for patients treated with NIVO+IPI within the CheckMate 214 trial. (B) OS by LIPI group for patients treated with sunitinib within the CheckMate 214 trial. (C) PFS by LIPI group and treatment type of patients treated within the CheckMate 214 trial.
See this image and copyright information in PMC

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