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Resume Le developpement de l’immunotherapie dans les cancers de la prostate est en plein essor. Le vaccin autologue, sipuleucel-T, est le premier vaccin approuve par la Food and Drug Administration (FDA) dans le cancer de la prostate. Les premiers resultats avec les vaccins ou molecules de type GVAX, tasquinimob ou anti-PD-1 sont plutot decevants. L’ipilimumab semble interessant a un stade precoce de la maladie metastatique. Les progres viendront de la meilleure comprehension du profil patient pouvant beneficier de ces immunomodulateurs. Les essais d’associations entre traitements immunomodulateurs et hormonotherapie ou traitements cibles osseux sont en plein developpement.

ImportanceThe role of cytoreductive nephrectomy in patients with metastatic renal cancer in the era of targeted therapy is uncertain.ObjectiveTo establish the safety and efficacy of upfront pazopanib therapy prior to cytoreductive nephrectomy in previously untreated patients with metastatic clear cell renal cancer.Design, Setting, and ParticipantsSingle-arm phase 2 study of 104 previously untreated patients with metastatic clear cell renal cancer recruited between June 2008 and October 2012 at cancer treatment centers with access to nephrectomy services. The minimum follow-up was 30 months.InterventionsPatients received 12 to 14 weeks of preoperative pazopanib therapy prior to planned cytoreductive nephrectomy and continued pazopanib therapy after surgery. Treatment was stopped at disease progression.Main Outcomes and MeasuresThe primary end point was clinical benefit (using Response Evaluation Criteria in Solid Tumors, version 1.1) prior to surgery (at 12-14 weeks). Secondary end points included surgical complications, progression-free survival (PFS), overall survival (OS), and biomarker analysis.ResultsOf 104 patients recruited, 100 patients were assessable for clinical benefit prior to planned nephrectomy; 80 of 104 (76.9%) were men; median [interquartile range] age, 64 [56-71] years). Overall, 84 of 100 (84% [95% CI, 75%-91%]) gained clinical benefit before planned nephrectomy. The median reduction in the size of the primary tumor was 14.4% (interquartile range, 1.4%-21.1%). No patients were unable to undergo surgery as a result of local progression of disease. Nephrectomy was performed in 63 (61%) of patients; 14 (22%) reported surgical complications. The 2 most common reasons for not undergoing surgery were progression of disease (n=13) and patient choice (n=9). There was 1 postoperative surgical death. The median PFS and OS for the whole cohort were 7.1 (95% CI, 6.0-9.2) and 22.7 (95% CI, 14.3-not estimable) months, respectively. Patients with MSKCC poor-risk disease or progressive disease prior to surgery had a poor outcome (median OS, 5.7 [95% CI, 2.6-10.8] and 3.9 [95% CI, 0.5-9.1] months, respectively). Surgical complications were observed in 14 (22%) of the nephrectomies. Biomarker analysis from sequential tissue samples revealed a decrease in CD8 expression (20.00 vs 13.75; P=.05) and significant reduction in expression of von Hippel–Lindau tumor suppressor (100 vs 40; PConclusions and RelevanceNephrectomy after upfront pazopanib therapy could be performed safely and was associated with good outcomes in patients with intermediate-risk metastatic clear cell renal cancer.