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| |  Antiangiogenesis Agent Pazopanib Well Tolerated, Offers Clinical Benefits in Patients With Advanced Renal Cell Carcinoma: Presented at EMUC By Chris Berrie BARCELONA, Spain -- December 1, 2009 -- Treatment with the oral multikinase angiogenesis inhibitor pazopanib is well tolerated and provides significant improvements in efficacy and quality of life for patients with advanced renal cell carcinoma (RCC), according to research presented here at the 2nd European Multidisciplinary Meeting on Urological Cancers (EMUC). Co-investigator Christy Ralph, MD, Cancer Research UK Department of Medical Oncology, University of Manchester and Christie Hospital NHS Foundation Trust, Manchester, United Kingdom, presented the results of the randomised, double-blind, phase 3 study here on November 27. Dr. Ralph indicated, “Renal cell carcinoma does not respond very well to standard chemotherapy, but has been shown to respond to antiangiogenic agents.” Thus, the aim of the study was to compare the efficacy and safety of pazopanib with placebo in this setting. Eligibility criteria included adult patients (>=18 years) with locally advanced and/or metastatic RCC, with clear-cell history, no prior treatment, or with 1 prior cytokine therapy. Patients needed to have measurable disease according to the Response Evaluation Criteria in Solid Tumours criteria, an Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1, and adequate organ function. The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall response rate (ORR), duration of response, overall survival (OS), and health-related quality of life (HRQOL); 435 patients were randomised 1:2 to placebo (n = 145) or pazopanib 800 mg QD (n = 290). The baseline characteristics across these treatment groups were similar for median age (60.0 vs 59.0 years, respectively), gender (male: 75% vs 68%), most common metastatic sites (lung/lymph node 73%/59% vs 74%/54%), ECOG PS 0/1 (41%/59% vs 42%/58%), and Memorial Sloan-Kettering Cancer Center (MSKCC) risk category (favourable/intermediate/poor/unknown: 39%/53%/3%/4% vs 39%/55%/3%/3%). There was significant improvement in median PFS for active treatment over placebo: 9.2 vs 4.2 months, respectively; hazard ratio (HR), 0.46 (95% confidence interval [CI], 0.34-0.62; P < .0000001). Similarly, when subdivided for previous cytokine use (pretreated: n = 67/135; naïve: n = 78/155), there was significant improvement with pazopanib for both the pretreated and naïve groups: HR, 0.54 (95% CI, 0.35-0.84; P < .001) and HR, 0.40 (95% CI, 0.27-0.60; P < .0000001), respectively. Further subgroup analyses for age, gender, MSKCC risk category, and ECOG PS also showed significant improvement in median PFS with pazopanib, with no significant subgroup effects. The ORR (complete plus partial responses) was increased, from 3% with placebo to 30% with active treatment, with a 58.7-week median duration of response. The ORR was again similar across the cytokine pretreated (3% vs 29%) and naïve (4% vs 32%) patients. At interim analysis, the median OS was improved, from 18.7 months for placebo to 21.1 months for pazopanib (HR, 0.73; 95% CI, 0.47-1.12; P < .02, 1-sided). Dr. Ralph also noted here that 48% of placebo patients received pazopanib after showing disease progression. The HRQOL measures were based on 3 prespecified self-reporting indices, with no clinically important differences shown across all 3: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30, EuroQol (EQ)-5D Index, and EQ-5D visual assessment scale. Thus, Dr. Ralph indicated, “There is no adverse effect on quality of life of taking the active drug, even though we know that there is toxicity with active drug.” “So [pazopanib] is an active agent with very interesting clinical activity that is not detrimental to the quality of life of the patients in an advanced disease setting,” she added. Funding for this study was sponsored by GlaxoSmithKline. EMUC was co-organised by the European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), and the European Society for Therapeutic Radiology and Oncology (ESTRO). [Presentation titles: A Randomized, Double-Blind, Phase III Study of Pazopanib in Treatment-Na¿ve and Cytokine-Pretreated Patients With Advanced Renal Cell Carcinoma (RCC). Abstract P085.
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