Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential targeted therapy.
Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab. The identification of predictive and prognostic factors of survival is increasing, and both clinical predictive factors and pathology-related prognostic factors are being evaluated. Serum-based biomarkers and certain histologic subtypes of RCC, as well as clinical factors such as dose intensity and the development of some class effect adverse events, have been identified as predictors of survival. Expression levels of microRNAs, expression of chemokine receptor 4, hypermethylation of certain genes, VEGF polymorphisms, and elevation of plasma fibrinogen or d-dimer have been shown to be prognostic indicators of survival. In the future, prognosis and treatment of patients with mRCC might be based on genomic classification, especially of the 4 most commonly mutated genes in RCC (VHL, PBRM1, BAP1, and SETD2). Median overall survival has improved for patients treated with a first-line targeted agent compared with survival of patients treated with first-line interferon-α, and results of clinical trials have shown a survival benefit of sequential treatment with targeted agents. Prognosis of patients with mRCC will likely improve with optimization and individualization of current sequential treatment with targeted agents.
Centro Integral Oncológico Clara Campal and START Madrid, Madrid, Spain. Electronic address: emiliano.calvo@start.stoh.com.
Emiliano
E
Calvo
Medical University of Vienna, Vienna, Austria.
Manuela
M
Schmidinger
Tom Baker Cancer Center, Calgary, Alberta, Canada.
Daniel Y C
DY
Heng
Hämatologie und Internistische Onkologie, Hannover, Germany.
Viktor
V
Grünwald
Institut Gustave Roussy, Villejuif, France.
Bernard
B
Escudier
D000813:Anilides / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077784:Axitinib; D000068258:Bevacizumab / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D004268:DNA-Binding Proteins; D000068338:Everolimus / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077594:Nivolumab; D009687:Nuclear Proteins / Q000235:genetics; D010671:Phenylurea Compounds / Q000627:therapeutic use; D057285:Precision Medicine / Q000379:methods; D011379:Prognosis; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D054398:Receptors, CCR4 / Q000235:genetics; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
D000813:Anilides; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D007093:Imidazoles; D007155:Immunologic Factors; D007191:Indazoles; D007211:Indoles; D016898:Interferon-alpha; D035683:MicroRNAs; D009687:Nuclear Proteins; C102195:PBRM1 protein, human; D010671:Phenylurea Compounds; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D011804:Quinolines; D054398:Receptors, CCR4; D013449:Sulfonamides; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C558660:cabozantinib; D009536:Niacinamide; D000068258:Bevacizumab; D000077594:Nivolumab; C401859:temsirolimus; C516667:pazopanib; D000068338:Everolimus; D000077157:Sorafenib; D000077784:Axitinib; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D043222:Ubiquitin Thiolesterase; C497446:VHL protein, human; C531958:lenvatinib; D000077210:Sunitinib; D020123:Sirolimus
Overall survival; Predictive markers; Prognostic markers; Sequential therapy; Targeted therapy; mRCC