Improved Survival of Real-world Japanese Patients With Advanced Renal Cell Carcinoma Treated With Immuno-oncology Combination Therapy

Background/Aim: Immuno-oncology (IO) combination therapy has become the standard of treatment for advanced renal cell carcinoma (RCC). In this retrospective study, we compared the efficacy of first-line molecular targeted therapy (MTT), administered as monotherapy, and IO combination therapy using real-world data of Japanese patients. Patients and Methods: The clinical information of 202 patients with RCC who received MTT (n=144) or IO combination therapy (n=58) at the Kurume University Hospital from May 2008 to May 2022 was collected and retrospectively analyzed. The Cox proportional hazards model was used for univariate and multivariate analyses, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated. Results: The patients treated with IO combination therapy had a prolonged progression-free survival (PFS) compared with those treated with MTT (p=0.0038). IO combination therapy was significantly associated with a better PFS in patients with intermediate (p=0.0072) and poor risk (p=0.0411) but not in those with favorable risk (p=0.5434). Furthermore, overall survival with IO combination therapy was significantly better in patients at poor risk (p=0.0335). Multivariate analyses suggested that prior nephrectomy (HR=1.501, 95%CI=1.048-2.150, p=0.0268) and first-line therapy (HR=1.962, 95%CI=1.288-2.986, p=0.0017) were independent prognostic factors for PFS. Conclusion: IO combination therapy significantly improved the PFS of patients with advanced RCC, especially those with intermediate- and poor-risk disease. Further investigations focusing on the improvement of survival are warranted.

[1]  C. Porta,et al.  Conditional survival and long‐term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma , 2022, Cancer.

[2]  K. Bensalah,et al.  The effect of immune checkpoint inhibitor combination therapies in metastatic renal cell carcinoma patients with and without previous cytoreductive nephrectomy: A systematic review and meta-analysis. , 2022, International immunopharmacology.

[3]  M. Oya,et al.  Predictors of Survival in Favorable Risk Patients with Metastatic Renal Cell Carcinoma Treated with a Single-Agent First-Line Therapy , 2022, Urologia Internationalis.

[4]  S. Hancock,et al.  Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. , 2022, Journal of the National Comprehensive Cancer Network : JNCCN.

[5]  N. Nonomura,et al.  Real-world Outcomes of Tyrosine Kinase Inhibitors Immediately After Immune Checkpoint Inhibitors in Renal Cell Carcinoma , 2021, AntiCancer Research.

[6]  K. Ueda,et al.  Absolute lymphocyte count is an independent predictor of survival in patients with metastatic renal cell carcinoma treated with nivolumab. , 2021, Japanese journal of clinical oncology.

[7]  Antonio P. DeRosa,et al.  Association between prior nephrectomy and efficacy of immune checkpoint inhibitor therapy in metastatic renal cell carcinoma - A systematic review and meta-analysis. , 2021, Urologic oncology.

[8]  H. Nishiyama,et al.  Prognosis of Japanese metastatic renal cell carcinoma patients in the targeted therapy era , 2021, International Journal of Clinical Oncology.

[9]  S. Buti,et al.  Impact of Previous Nephrectomy on Clinical Outcome of Metastatic Renal Carcinoma Treated With Immune-Oncology: A Real-World Study on Behalf of Meet-URO Group (MeetUro-7b) , 2021, Frontiers in Oncology.

[10]  C. Porta,et al.  Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. , 2021, The New England journal of medicine.

[11]  M. Oya,et al.  Efficacy and safety of subsequent molecular targeted therapy after immuno-checkpoint therapy, retrospective study of Japanese patients with metastatic renal cell carcinoma (AFTER I-O study) , 2021, Japanese journal of clinical oncology.

[12]  C. Porta,et al.  Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. , 2021, The New England journal of medicine.

[13]  M. Yoshino,et al.  Efficacy of Cabozantinib in Metastatic Papillary Renal Cell Carcinoma Following Ineffective Treatment With Initial Therapy of Nivolumab and Ipilimumab , 2021, In Vivo.

[14]  Kazuhiko Yoshida,et al.  Predictive impact of an early change in serum C-reactive protein levels in nivolumab therapy for metastatic renal cell carcinoma. , 2019, Urologic oncology.

[15]  R. Figlin,et al.  The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC) , 2019, Journal of Immunotherapy for Cancer.

[16]  C. Porta,et al.  Efficacy of Nivolumab plus Ipilimumab According to Number of IMDC Risk Factors in CheckMate 214. , 2019, European urology.

[17]  Kazuhiko Yoshida,et al.  Predictive Impact of Peripheral Blood Markers and C-Reactive Protein in Nivolumab Therapy for Metastatic Renal Cell Carcinoma , 2019, Targeted Oncology.

[18]  T. Powles,et al.  Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal‐Cell Carcinoma , 2019, The New England journal of medicine.

[19]  R. Motzer,et al.  Avelumab plus Axitinib versus Sunitinib for Advanced Renal‐Cell Carcinoma , 2019, The New England journal of medicine.

[20]  R. Figlin,et al.  Sunitinib in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to International Metastatic Renal Cell Carcinoma Database Consortium Risk Group , 2018, Clinical genitourinary cancer.

[21]  Bohuslav Melichar,et al.  Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal‐Cell Carcinoma , 2018, The New England journal of medicine.

[22]  Jason Zhu,et al.  Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond , 2018, Journal of Immunotherapy for Cancer.

[23]  Kazuhiko Yoshida,et al.  Time to progression after first-line tyrosine kinase inhibitor predicts survival in patients with metastatic renal cell carcinoma receiving second-line molecular-targeted therapy. , 2017, Urologic oncology.

[24]  A. Ravaud,et al.  Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. , 2015, The New England journal of medicine.

[25]  K. Ueda,et al.  Duration of First-line Treatment with Molecular Targeted-Therapy Is a Prognostic Factor in Metastatic Renal Cell Carcinoma. , 2015, Anticancer research.

[26]  Razelle Kurzrock,et al.  PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy , 2015, Molecular Cancer Therapeutics.

[27]  T. Choueiri,et al.  External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. , 2013, The Lancet. Oncology.