臨床泌尿器科77巻5号

2023年04月発行

特集 どこまで変わるの？　腎細胞癌診療の進歩 〈薬物治療〉

逐次療法

著者： 高橋正幸¹ 金山博臣¹

所属機関： ¹徳島大学大学院医歯薬学研究部泌尿器科学分野

ページ範囲：P.378 - P.387

▶ポイント

・一次治療がニボルマブ＋イピリムマブ併用療法の場合，逐次療法では，どのVEGFR-TKIも高い有効性が示されている．

・一次治療が免疫チェックポイント阻害薬＋血管内皮細胞増殖因子受容体―チロシンキナーゼ阻害薬（VEGFR-TKI）の場合，カボザンチニブやスニチニブの有効性が示されている．

・今後，逐次療法として免疫チェックポイント阻害薬＋VEGFR-TKIやHIF-2阻害薬などの新しい治療法が期待されている．

参考文献

1） Motzer RJ, et al : Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma : Final Results and Analysis of Prognostic Factors. Cancer 116 : 4256-4265, 2010

2） Rini BI, et al : Comparative Effectiveness of Axitinib versus Sorafenib in Advanced Renal Cell Carcinoma （AXIS） : A Randomised Phase 3 Trial. Lancet 378 : 1931-1939, 2011

3） Vickers MM, et al : Clinical Outcome in Metastatic Renal Cell Carcinoma Patients After Failure of Initial Vascular Endothelial Growth Factor-Targeted Therapy. Urology 76 : 430-434, 2010

4） Harrison MR, et al : Outcomes of “Real World” Treatment for Metastatic Renal Cell Carcinoma （mRCC）. J Clin Oncol 30 （Suppl 5） : 406, 2012

5） Heng DY, et al : Primary Anti-Vascular Endothelial Growth Factor （VEGF） -Refractory Metastatic Renal Cell Carcinoma : Clinical Characteristics, Risk Factors, and Subsequent Therapy. Ann Oncol 23 : 1549-1555, 2012

6） Hutson TE, et al : Randomized Phase III Trial of Temsirolimus versus Sorafenib as Second-Line Therapy After Sunitinib in Patients with Metastatic Renal Cell Carcinoma. J Clin Oncol 32 : 760-767, 2014

7） Motzer RJ, et al : Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 373 : 1803-1813, 2015

8） Motzer RJ, et al : Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 378 : 1277-1290, 2018

9） Motzer RJ, et al : Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 380 : 1103-1115, 2019

10） Rini BI, et al : Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 380 : 1116-1127, 2019

11） Choueiri TK, et al : Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 384 : 829-841, 2021

12） Motzer R, et al : Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med 384 : 1289-1300, 2021

13） Auvray M, et al : Second-Line Targeted Therapies After Nivolumab-Ipilimumab Failure in Metastatic Renal Cell Carcinoma. Eur J Cancer 108 : 33-40, 2019

14） Tomita Y, 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）. Jpn J Clin Oncol 51 : 966-975, 2021

15） Dudani S, et al : First-Line Immuno-Oncology Combination Therapies in Metastatic Renal-Cell Carcinoma : Results from the International Metastatic Renal-Cell Carcinoma Database Consortium. Eur Urol 76 : 861-867, 2019

16） Stukalin I, et al : Second-Line VEGF TKI After IO Combination Therapy : Results from the International Metastatic Renal Cell Carcinoma Database Consortium （IMDC）. J Clin Oncol 38 （Supple 6） : 684, 2020

17） Choueiri TK, et al : Updated Efficacy Results from the JAVELIN Renal 101 Trial : First-Line Avelumab plus Axitinib versus Sunitinib in Patients with Advanced Renal Cell Carcinoma. Ann Oncol 31 : 1030-1039, 2020

18） Rini BI, et al : Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 380 : 1116-1127, 2019

19） Choueiri TK, et al : Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 373 : 1814-1823, 2015

20） Choueiri TK, et al : Cabozantinib versus Everolimus in Advanced Renal Cell Carcinoma （METEOR） : Final Results from a Randomised, Open-Label, Phase 3 Trial. Lancet Oncol 17 : 917-927, 2016

21） Fitzgerald KN, et al : Progression-Free Survival After Second Line of Therapy for Metastatic Clear Cell Renal Cell Carcinoma in Patients Treated with First-Line Immunotherapy Combinations. Eur Urol, 2022 ［Online ahead of print］

22） Ornstein MC, et al : Individualised Axitinib Regimen for Patients with Metastatic Renal Cell Carcinoma After Treatment with Checkpoint Inhibitors : A Multicentre, Single-Arm, Phase 2 Study. Lancet Oncol 20 : 1386-1394, 2019

23） Cao X, et al : Real-World Clinical Outcomes of Pazopanib Immediately After Discontinuation of Immunotherapy for Advanced Renal Cell Carcinoma. Clin Genitourin Cancer 18 : e37-e45, 2020

24） Grande E, et al : Results from the INMUNOSUN-SOGUG Trial : A Prospective Phase II Study of Sunitinib as a Second-Line Therapy in Patients with Metastatic Renal Cell Carcinoma After Immune Checkpoint-Based Combination Therapy. ESMO Open 7 : 100463, 2022

25） Wells JC, et al : Clinical Effectiveness of Second-Line Sunitinib Following Immuno-Oncology Therapy in Patients with Metastatic Renal Cell Carcinoma : A Real-World Study. Clin Genitourin Cancer 19 : 354-361, 2021

26） McGregor BA, et al : Activity of Cabozantinib After Immune Checkpoint Blockade in Metastatic Clear-Cell Renal Cell Carcinoma. Eur J Cancer 135 : 203-210, 2020

27） Procopio G, et al : A Multicenter Phase 2 Single Arm Study of Cabozantinib in Patients with Advanced or Unresectable Renal Cell Carcinoma Pre-treated with One Immune-Checkpoint Inhibitor : The BREAKPOINT Trial （Meet-Uro trial 03）. Tumori 109 : 129-137, 2023

28） Santoni M, et al : Cabozantinib in Patients with Advanced Renal Cell Carcinoma Primary Refractory to First-Line Immunocombinations or Tyrosine Kinase Inhibitors. Eur Urol Focus 8 : 1696-1702, 2022

29） Ravi P, et al : Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients with Renal Cell Carcinoma. JAMA Oncol 6 : 1606-1610, 2020

30） Lee CH, et al : Lenvatinib plus Pembrolizumab in Patients with Either Treatment-Naive or Previously Treated Metastatic Renal Cell Carcinoma （Study 111/KEYNOTE-146） : A Phase 1b/2 Study. Lancet Oncol 22 : 946-958, 2021

31） Choueiri TK, et al : Inhibition of Hypoxia-Inducible Factor-2α in renal cell carcinoma with Belzutifan : A Phase 1 Trial and Biomarker Analysis. Nat Med 27 : 802-805, 2021