Alain Ravaud

Axitinib: A Review of its Safety and Efficacy in the Treatment of Adults with Advanced Renal Cell Carcinoma

Over the last seven years, seven targeted agents have been approved in the treatment of advanced or metastatic renal cell cancer, changing the therapeutic approach and prognosis of the disease dramatically. The latest agent with demonstrated efficacy is axitinib (Inlyta®). This new generation of tyrosine kinase agent differs from previously existing agents by its greater activity potency of inhibition of vascular endothelial growth factor-receptor (VEGFR1-3). This efficacy has been tested in phase II and III clinical trials. Axitinib is the only targeted agent that benefits from recommended titration, with intra-patient dose escalation. The toxicity profile of the drug is tolerable. This paper reviews the mechanism of action of axitinib, its metabolism, and its pharmacokinetic profile. Clinical data of efficacy and safety is also detailed. The agent has been integrated in the international therapeutic guidelines, as a standard in treatment of renal cell cancer patients, previously treated through antiangiogenic therapy.

Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma

BACKGROUND Cytoreductive nephrectomy has been the standard of care in metastatic renal‐cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal‐cell carcinoma who were receiving targeted therapies. METHODS In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear‐cell renal‐cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow‐up was 50.9 months, with 326 deaths observed. The results in the sunitinib‐alone group were noninferior to those in the nephrectomy–sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib‐alone group and 13.9 months in the nephrectomy–sunitinib group. No significant differences in response rate or progression‐free survival were observed. Adverse events were as anticipated in each group. CONCLUSIONS Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal‐cell carcinoma who were classified as having intermediate‐risk or poor‐risk disease. (Funded by Assistance Publique–Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033.)

Quelle pratique de la néphrectomie partielle en France ? [What is the clinical practice of partial nephrectomy in France?]

OBJECTIVEnTo describe the practice of partial nephrectomy (PN) in France and assess its results in terms of morbidity and cancer control.nnnMATERIAL AND METHODnSeven French University Hospitals in which nephron sparing surgery represents at least 30% of the total number of nephrectomies for renal tumour, participated in this study. All centres included, as exhaustively as possible, all their PN cases. For each patient, 70 variables were harvested in order to characterize the patient population, the indications, the operative technique, the per- and postoperative course and complications, the tumor specificities, the carcinologic control and renal function follow-up.nnnRESULTSnSeven hundred and forty-one PN, of which 579 for malignant tumours were analysed. The mean tumour size was 3.4+/-2.1 cm (0.1-18) and 20.8% of the tumours were larger than 4 cm. In 30.1% of cases, the indication was imperative. Among the PN, 12.2% were performed laparoscopically. The mean operating time was 151+/-54.2 min (55-420). The medical and surgical complications rates were respectively 15.2 and 14.7%. At a mean 38 months follow-up, the local recurrence rate was 3.5% and the specific death rate was 4.5%.nnnCONCLUSIONnPN is nowadays getting a more and more widely used technique in France. This expansion is completely justified by its results and urologists must consider nephron sparing surgery as the gold standard treatment for renal tumours measuring less than 4 cm.

Intérêt des anti-angiogéniques dans le cancer du rein localement avancé et métastatique en situation néo-adjuvante : à propos de 2 cas

Resume Les anti-angiogeniques ont prouve un benefice dans le cancer du rein en situation metastatique. Nous presentons ici deux cas cliniques montrant l’efficacite des anti-angiogeniques en situation localement avancee ou metastatique, ou une importante necrose tumorale a modifie la prise en charge de la maladie, notamment la prise en charge chirurgicale. La place des traitements anti angiogeniques en situation adjuvante ou neo-adjuvante reste encore a definir. Toutefois, ces nouveaux traitements ouvrent des perspectives therapeutiques reelles pour l’exerese eventuelle de masse renale initialement inextirpable ou en cas de recidive precoce apres chirurgie.

Quelle place pour les stratégies médicales adjuvante et néoadjuvante en phase localisée

Dans une vue tres schematique, il existe trois grands groupes de cancers du rein en termes de risque pronostique. Un premier groupe est celui qui a une tres grande probabilite ďetre gueri par la chirurgie seule. Il est communement admis que les tumeurs qui correspondent a ce groupe sont des tumeurs confinees au rein (<pT2), de bas grade, incidentales. Un deuxieme groupe comprend des patients avec des tumeurs qui ont un risque significatif de ne pas etre gueries de maniere durable par la chirurgie, meme si ľexerese est macroscopique, complete, et meme s’il nexiste pas de metastases au moment du diagnostic. Il s’agira volontiers dans ce cas de tumeurs symptomatiques, de grande taille, de haut grade ou localement avancees. Le troisieme groupe est celui qui na aucune chance ďetre gueri par la chirurgie seule et cest typiquement le groupe des patients metastatiques pour lequel un traitement systemique est requis avec ou sans nephrectomie.