J O U R N A L C L U B Essential Peer-Reviewed Reading in Kidney Cancer The peer-reviewed articles summarized in this section were selected by the Guest Editor, Bernard J. Escudier, MD, for their timeliness, importance, relevance, and potential impact on clinical practice or translational research. Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma. Motzer RJ, Haas NB, Donskov, et al. J Clin Oncol. 2017 Sep 13; JCO2017735324. doi: 10.1200/JCO.2017.73. 5324. Summary: This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. A total of 1,538 patients with resected pT2 (high grade) or �� pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intentto treat (ITT) pazopanib 600 mg group (ITT600mg), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT800mg) and safety. The primary analysis results of DFS ITT600mg favored pazopanib but did not show a significant improvement over placebo (P = .165). The secondary analysis of DFS in ITT800mg (n = 403) yielded an HR of 0.69. Follow-up analysis in ITT600mg yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion: The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting. Long-Term Response to Sunitinib Treatment in Metastatic Renal Cell Carcinoma: A Pooled Analysis of Clinical Trials. Tannir NM, Figlin RA, Gore ME, et al. EClin Genitourin Cancer. 2017 Jun 20. S1558-7673(17) 30171-4. Summary: We characterized clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib who were long-term responders (LTRs), defined as patients having progression-free survival (PFS) > 18 months. A retrospective analysis of data from 5714 patients with mRCC treated with sunitinib in 8 phase II/III clinical trials and the expanded access program. Duration on-study and objective response rate (ORR) were compared between LTRs and patients with PFS �� 18 months (“others”). PFS and overall survival (OS) were summarized using Kaplan-Meier methodology. Overall, 898 (15.7%) patients achieved a long-term response and 4816 (84.3%) patients did not achieve long-term response. The median (range) duration on-study was 28.6 (16.8-70.7) months in LTRs and 5.5 (0-68.8) months in others. ORR was 51% in LTRs versus 14% in others (P < .0001). Median PFS in LTRs was 32.11 months and median OS was not reached. LTRs had higher percentage of early tumor shrinkage �� 10% at the first scan (67.1% vs. 51.2%; P = .0018) and greater median maximum on-study tumor shrinkage from baseline (-56.9 vs. -27.1; P < .0001) versus others. Conclusion: White race, Eastern Cooperative Oncology Group performance status 0, time from diagnosis to treatment �� 1 year, clear cell histology, no liver metastasis, lactate dehydrogenase �� 1.5 upper limit of normal (ULN), corrected calcium �� 10 mg/dL, hemoglobin greater than the lower limit of normal, platelets less than or equal to ULN, body mass index �� 25 kg/m2, and low neutrophilto lymphocyte ratio were associated with LTR. A subset of patients with mRCC treated with sunitinib achieved longterm response. LTRs had improved ORR, PFS, and OS. Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer. Choueiri TK, Plimack E, Arkenau HT, et al. J Clin Oncol. 2017 Sep 10;35(26):2993-3001. doi: 10.1200/JCO.2017.72.2967 Summary: Patients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status. Patients and Methods Patients with histologically confirmed locally advanced or metastatic PRCC were enrolled and received savolitinib 600 mg orally once daily. MET-driven PRCC was defined as any of the following: chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations. Efficacy was assessed according to MET status. Safety, toxicity, and patient-reported health-related quality-of-life outcomes were assessed in all patients. Results Of 109 patients treated, PRCC was MET driven in 44 (40%) and MET independent in 46 (42%); MET status was unknown in 19 (17%). MET-driven PRCC was strongly associated with response; there were eight confirmed partial responders 64 Kidney Cancer Journal (continued on page 81)
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