Advertisement

Nivolumab VERSUS Cabozantinib as Second-Line Therapy in Patients With Advanced Renal Cell Carcinoma: A Real-World Comparison

Published:February 19, 2022DOI:https://doi.org/10.1016/j.clgc.2022.02.003

      Highlights

      • Herein, we investigated the real-world efficacy of nivolumab and cabozantinib as second-line therapy in a cohort of 343 patients in a real-world setting.
      • We observed an advantage for nivolumab in terms of overall survival (OS) in almost all the subgroups analyzed, without reporting a statistically significant difference, except for patients with bone metastases or progressed during first-line sunitinib, characterized by longer survival with cabozantinib.
      • Median progression-free survival (PFS) was higher with cabozantinib in the majority of the subgroup analyses and resulted statistically significantly longer in male patients, in clear cell renal cell carcinoma (ccRCC) histology and in the good risk subgroup.
      • According to our results, nivolumab and cabozantinib were active in mRCC patients, showing distinct results when stratified into clinico-pathological features.

      Abstract

      Background

      Tyrosine-kinase inhibitors (TKIs) still represent a first-line option for selected patients with metastatic Renal Cell Carcinoma (mRCC). We aimed to compare the real-world efficacy of nivolumab or cabozantinib as second-line therapy in specific mRCC subpopulations.

      Patients and Methods

      We retrospectively collected data from 11 centers from Italy, Spain and US. Overall Survival (OS) and Progression-Free Survival (PFS) were analyzed using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.

      Results

      We collected data from 343 patients with mRCC, 123 (36%) treated with cabozantinib and 220 (64%) with nivolumab. The median OS resulted longer, but not statistically significant, with nivolumab in patients aged >70 years (21.4 vs. 15.4 months, P = .746), treated with first-line pazopanib (26.8 vs. 11.6 months, P = .450), or with good (47.0 vs. 15.5 months, P = .285) or intermediate-risk criteria (14.4 vs. 11.0 months, P = .357), while it was longer, but even not statistically significant, for cabozantinib in patients who received previous sunitinib (25.7 vs. 21.7 months, P = .638) or with bone metastases (28.4 vs. 24.4 months, P = .871). The median PFS was significantly longer with cabozantinib in patients with clear cell histology (7.8 vs. 5.4 months, P = .026) and in patients with good risk features (12.3 vs. 5.7 months, P = .022).

      Conclusions

      Nivolumab and cabozantinib resulted active in mRCC patients, showing distinct results when stratified into clinico-pathological features.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Siegel RL
        • Miller KD
        • Jemal A.
        Cancer statistics.
        CA Cancer J Clin. 2019; 69 (2019 Jan): 7-34
        • Moch H
        • Cubilla AL
        • Humphrey PA
        • et al.
        The 2016 WHO classification of tumours of the urinary system and male genital organs-Part A: Renal, Penile, and Testicular Tumours.
        Eur Urol. 2016; 70: 93-105
        • Allemani C
        • Matsuda T
        • Di Carlo V
        • et al.
        Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries.
        Lancet. 2018; 391: 1023-1075
        • Rini BI
        • Plimack ER
        • Stus V
        • et al.
        Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.
        N Engl J Med. 2019; 380: 1116-1127
        • Motzer R
        • Alekseev B
        • Rha SY
        • et al.
        Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.
        N Engl J Med. 2021; 384: 1289-1300
        • Motzer RJ
        • Penkov K
        • Haanen J
        • et al.
        Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.
        N Engl J Med. 2019; 380: 1103-1115
        • Choueiri TK
        • Powles T
        • Burotto M
        • et al.
        Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma.
        N Engl J Med. 2021; 384: 829-841
        • Motzer RJ
        • Powles T
        • Atkins MB
        • et al.
        Final overall survival and molecular analysis in immotion151, a phase 3 trial comparing atezolizumab plus bevacizumab vs sunitinib in patients with previously untreated metastatic renal cell carcinoma.
        JAMA Oncol. 2021; https://doi.org/10.1001/jamaoncol.2021.5981
        • Motzer RJ
        • Tannir NM
        • McDermott DF
        • et al.
        Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma.
        N Engl J Med. 2018; 378: 1277-1290
        • Heng DY
        • Xie W
        • Regan MM
        • et al.
        Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.
        J Clin Oncol. 2009; 27: 5794-5799
        • Motzer RJ
        • Hutson TE
        • Tomczak P
        • et al.
        Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.
        N Engl J Med. 2007; 356: 115-124
        • Sternberg CN
        • Davis ID
        • Mardiak J
        • et al.
        Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial.
        J ClinOncol. 2010; 28: 1061-1068
        • Schwartz LH
        • Litière S
        • de Vries E
        • et al.
        RECIST 1.1-Update and clarification: From the RECIST committee.
        Eur J Cancer. 2016; 62: 132-137
        • Aragon-Ching JB.
        Balancing efficacy and quality of life measurements among metastatic renal cell carcinoma (RCC) studies.
        Oncoscience. 2021 Mar 21; 8: 40-45
        • Rizzo A
        • Mollica V
        • Dall'Olio FG
        • et al.
        Quality of life assessment in renal cell carcinoma Phase II and III clinical trials published between 2010 and 2020: a systematic review.
        Future Oncol. 2021; 17: 2671-2681
        • PÁ Ballesteros
        • J Chamorro
        • Román-Gil MS
        • et al.
        Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma.
        Cancers (Basel). 2021; 13: 5981
        • Sharma R
        • Kadife E
        • Myers M
        • Kannourakis G
        • Prithviraj P
        • Ahmed N.
        Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma.
        J ExpClinCancer Res. 2021; 40: 186
        • Guadalupi V
        • Cartenì G
        • Iacovelli R
        • et al.
        Second-line treatment in renal cell carcinoma: clinical experience and decision making.
        Ther Adv Urol. 2021; 1317562872211022870
        • Schmidinger M.
        Clinical decision-making for immunotherapy in metastatic renal cell carcinoma.
        Curr Opin Urol. 2018; 28: 29-34
        • Scholtes MP
        • Alberts AR
        • Iflé IG
        • et al.
        Biomarker-Oriented Therapy in Bladder and Renal Cancer.
        Int J Mol Sci. 2021; 22: 2832
        • Heo JH
        • Park C
        • Ghosh S
        • et al.
        A network meta-analysis of efficacy and safety of first-line and second-line therapies for the management of metastatic renal cell carcinoma.
        J ClinPharmTher. 2021; 46: 35-49
        • Porta C
        • Szczylik C
        • Casciano R
        • et al.
        Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison.
        Crit Rev Oncol Hematol. 2019; 139: 143-148
        • Escudier B
        • Sharma P
        • McDermott DF
        • et al.
        CheckMate 025 Randomized Phase 3 Study: outcomes by key baseline factors and prior therapy for nivolumab versus everolimus in advanced renal cell carcinoma.
        Eur Urol. 2017; 72: 962-971
        • Zizzari IG
        • Napoletano C
        • Botticelli A
        • et al.
        TK Inhibitor Pazopanib Primes DCs by Downregulation of the β-Catenin Pathway.
        Cancer Immunol Res. 2018; 6: 711-722
        • Santoni M
        • Heng DY
        • Bracarda S
        • Procopio G
        • Milella M
        • Porta C
        • et Al.
        Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors.
        Cancers (Basel). 2019; 12: 84
        • Iacovelli R
        • Ciccarese C
        • Facchini G
        • Milella M
        • Urbano F
        • Basso U
        • et al.
        Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis.
        Target Oncol. 2020; 15: 495-501
        • Escudier B
        • Powles T
        • Motzer RJ
        • et al.
        Cabozantinib, a new standard of care for patients with advanced renal cell carcinoma and bone metastases? Subgroup analysis of the METEOR Trial.
        J Clin Oncol. 2018; 36: 765-772
        • Fioramonti M
        • Santini D
        • Iuliani M
        • et al.
        Cabozantinib targets bone microenvironment modulating human osteoclast and osteoblast functions.
        Oncotarget. 2017; 8: 20113-20121https://doi.org/10.18632/oncotarget.15390