Targeted therapies and complete responses in first line treatment of metastatic renal cell carcinoma. A meta-analysis of published trials.
Antiangiogenic agents (AAs) have reported grater efficacy compared to interferon. Despite these advances, radiological complete response to therapy is rare. We meta-analyzed the incidence of complete response in patients treated with AAs and in controls in main randomized clinical trials for first-line therapy in metastatic renal cell carcinoma. PubMed was reviewed for phase II-III randomized clinical trials with AAs vs. non-AAs in patients with good or intermediate prognosis. We calculated the relative risk of events in patients assigned to AAs compared to control. Five RCTs were found; four were phase III and one was phase II. A total of 2747 patients was valuable for final analysis and randomized to receive AAs or control. Patients in the control-group had interferon (85%) or placebo (15%); patients in the AAs-group received bevacizumab (48%), sunitinib (26%), pazopanib (20%) or sorafenib (6%). The incidence of complete response in patients treated with AAs was 2.0% (95% CI, 1.2-2.8) compared to 1.4% (95% CI, 0.7-2.1) in the control arm. Comparing the different type of AAs, the incidence of complete response was 2.5% (95% CI, 1.2-3.8) in the bevacizumab group and 1.6% (95% CI, 0.1-2.5) in the TKIs group. The relative risk to have a complete response was 1.52 (95% CI, 0.85-2.73; p=0.16) in patients treated with AAs compared to controls; this was found higher in patients treated with TKIs compared to bevacizumab. The complete response is a rare event in metastatic kidney tumor, even if AAs reported greater efficacy in terms of progression-free survival and of overall response rate, they did not increase the curative rate of metastatic disease. Probably, some biologic factors other than angiogenesis may influence the complete response in this disease.
"Sapienza" University of Rome, Department of Radiology, Oncology and Human Pathology, Viale Regina Elena 324, 00161 Rome, Italy. Electronic address: roberto.iacovelli@alice.it.
Roberto
R
Iacovelli
Daniele
D
Alesini
Antonella
A
Palazzo
Patrizia
P
Trenta
Matteo
M
Santoni
Laura
L
De Marchis
Stefano
S
Cascinu
Giuseppe
G
Naso
Enrico
E
Cortesi
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000008:administration & dosage; D060828:Induction Chemotherapy / Q000379:methods; D007372:Interferons / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D000077157:Sorafenib; D013449:Sulfonamides / Q000008:administration & dosage; D000077210:Sunitinib; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; D000068258:Bevacizumab; C516667:pazopanib; D007372:Interferons; D000077157:Sorafenib; D000077210:Sunitinib
Antiangiogenic agents; Bevacizumab; Complete response; Cytokines; Interferon; Metastatic renal cells cancer; Pazopanib; Sorafenib; Sunitinib