First-line antiangiogenics for metastatic renal cell carcinoma: A systematic review and network meta-analysis.
BACKGROUND
Sunitinib, pazopanib, sorafenib, axitinib and bevacizumab are the five recommended antiangiogenic agents in first-line therapy for metastatic renal cell carcinoma (mRCC). Because these drugs underwent simultaneous clinical development, no direct efficacy and safety comparison was ever conducted, thus preventing optimal therapy choices.


METHODS
We performed a traditional and network meta-analysis to evaluate the efficacy and safety of mRCC-recommended first-line antiangiogenic agents. After a systematic review of Medline and Embase up to July 2014, we identified randomized clinical trials (RCTs) evaluating the outcomes of mRCC patients treated with sunitinib, pazopanib, sorafenib, axitinib and bevacizumab as first-line treatment. Endpoints of interest were response rate, progression-free survival (PFS), overall survival (OS), and safety.


RESULTS
We screened 769 abstracts and included nine RCTs with a total of 4282 patients. In the weighted pooled analysis, first-line antiangiogenic agents showed significant improvement in PFS (HR=0.6; 95% IC, 0.51-0.72) and OS (HR=0.85; 95% IC, 0.78-0.93) compared to control (placebo or interferon-alpha2a (INF)). Network meta-analysis showed no significant differences among antiangiogenic drugs in 6-month PFS, 1-year OS, disease control rate and drug-related safety for all-grade hypertension, diarrhea, weight-loss, nausea or anorexia. However, pazopanib showed a lower incidence of fatigue, anemia and hand foot skin reaction.


CONCLUSIONS
This meta-analysis confirms the benefits of first-line antiangiogenic therapy in mRCC, with an improvement in OS. Sunitinib, pazopanib, axitinib and bevacizumab + INF offer similar efficacy but different safety profiles which can help clinicians to better personalize treatment decisions in patients with mRCC.
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France; INSERM, U955, Team 18, Créteil, France. Electronic address: benoit.rousseau@aphp.fr.
Benoît
B
Rousseau
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
Emmanuelle
E
Kempf
Huntington Center, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, France.
Gaelle
G
Desamericq
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
Emilie
E
Boissier
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France.
Marie
M
Chaubet-Houdu
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France.
Charlotte
C
Joly
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France.
Carolina
C
Saldana
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France.
Helene
H
Boussion
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France.
Cindy
C
Neuzillet
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France.
Isabelle
I
Macquin-Mavier
Department of Medical Oncology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Stéphane
S
Oudard
University of Paris-Est, Faculty of Medicine, Créteil, France; Department of Urology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
Laurent
L
Salomon
University of Paris-Est, Faculty of Medicine, Créteil, France; Department of Urology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
Alexandre
A
de la Taille
Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France.
Christophe
C
Tournigand
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors
Angiogenesis inhibitors; Meta-analysis; Renal cell carcinoma