Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial

Purpose Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). Patients and Methods Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2: 1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. Conclusion Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC. J Clin Oncol 28: 1061-1068. (C) 2010 by American Society of Clinical Oncology*US DEP HHS, 2009, CANC INC SURV EP ENDRini BI, 2008, J CLIN ONCOL, V26, P5422, DOI 10.1200/JCO.2008.16.9847Hutson T, 2008, ANN ONCOL, V19, P187Motzer RJ, 2008, LANCET, V372, P449, DOI 10.1016/S0140-6736(08)61039-9Coppin C, 2008, EXPERT REV ANTICANC, V8, P907, DOI 10.1586/14737140.8.6.907Karaman MW, 2008, NAT BIOTECHNOL, V26, P127, DOI 10.1038/nbt1358Coppin C, 2008, COCHRANE DB SYST REV, DOI 10.1002/14651858.CD006017.pub2CURADO M, 2008, CANC INCIDENCE 5 CON, V9HUTSON TE, 2008, J CLIN ONCOL, V26, pS261Pickard AS, 2007, HEALTH QUAL LIFE OUT, V5, DOI 10.1186/1477-7525-5-70Escudier B, 2007, LANCET, V370, P2103Negrier S, 2007, CANCER, V110, P2468, DOI 10.1002/cncr.23056Motzer RJ, 2007, J UROLOGY, V178, P1883, DOI 10.1016/j.juro.2007.07.030Hudes G, 2007, NEW ENGL J MED, V356, P2271Nelson EC, 2007, CANCER TREAT REV, V33, P299, DOI 10.1016/j.ctrv.2006.12.005Motzer RJ, 2007, NEW ENGL J MED, V356, P115Escudier B, 2007, NEW ENGL J MED, V356, P125van Spronsen DJ, 2005, ANTI-CANCER DRUG, V16, P709Hurwitz H, 2005, J CLIN ONCOL, V23, p195SRabin R, 2001, ANN MED, V33, P337Therasse P, 2000, J NATL CANCER I, V92, P205Motzer RJ, 1999, J CLIN ONCOL, V17, P2530DIAZ JI, 1999, CANC CONTROL, V6, P571Osoba D, 1998, J CLIN ONCOL, V16, P139AARONSON NK, 1993, J NATL CANCER I, V85, P365*NAT CANC I CANC T, COMM TERM CRIT ADV E20

Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial

Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC.publisher: Elsevier articletitle: Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial journaltitle: The Lancet Oncology articlelink: http://dx.doi.org/10.1016/S1470-2045(16)00099-1 associatedlink: http://dx.doi.org/10.1016/S1470-2045(16)30031-6 content_type: article copyright: © 2016 Elsevier Ltd. All rights reserved.status: publishe

Tomorrow's Europe : the views of those concerned

845 p., ref. bib. : 37 p