Journal ArticleDOI
Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial
Thomas E. Hutson,Vladimir Lesovoy,Salman Al-Shukri,Viktor Stus,Oleg Lipatov,Angel H. Bair,Brad Rosbrook,Connie Chen,Sinil Kim,Nicholas J. Vogelzang +9 more
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TLDR
Axitinib did not significantly increase progression-free survival in patients with treatment-naive metastatic renal-cell carcinoma compared with those treated with sorafenib, but did demonstrate clinical activity and an acceptable safety profile.Abstract:
Summary Background In previous clinical trials of patients with metastatic renal-cell carcinoma, patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib. We therefore undertook a phase 3 trial comparing axitinib with sorafenib in patients with treatment-naive metastatic renal-cell carcinoma. Methods In this randomised, open-label, phase 3 trial, patients with treatment-naive, measurable, clear-cell metastatic renal-cell carcinoma from 13 countries were stratified by Eastern Cooperative Oncology Group performance status, and then randomly assigned (2:1) by a centralised registration system to receive axitinib 5 mg twice daily, or sorafenib 400 mg twice daily. The primary endpoint was progression-free survival, assessed by masked independent review committee in the intention-to-treat population. This ongoing trial is registered at ClinicalTrials.gov, NCT00920816. Findings Between June 14, 2010, and April 21, 2011, we randomly assigned 192 patients to receive axitinib, and 96 patients to receive sorafenib. The cutoff date for this analysis was July 27, 2012, when 171 (59%) of 288 patients died or had disease progression, as assessed by the independent review committee. There was no significant difference in median progression-free survival between patients treated with axitinib or sorafenib (10·1 months [95% CI 7·2–12·1] vs 6·5 months [4·7–8·3], respectively; stratified hazard ratio 0·77, 95% CI 0·56–1·05). Any-grade adverse events that were more common (≥10% difference) with axitinib than with sorafenib were diarrhoea (94 [50%] of 189 patients vs 38 [40%] of 96 patients), hypertension (92 [49%] vs 28 [29%]), weight decrease (69 [37%] vs 23 [24%]), decreased appetite (54 [29%] vs 18 [19%]), dysphonia (44 [23%] vs ten [10%]), hypothyroidism (39 [21%] vs seven [7%]), and upper abdominal pain (31 [16%] vs six [6%]); those more common with sorafenib than with axitinib included palmar-plantar erythrodysaesthesia (PPE; 37 [39%] of 96 patients vs 50 [26%] of 189), rash (19 [20%] vs 18 [10%]), alopecia (18 [19%] vs eight [4%]), and erythema (18 [19%] vs five [3%]). The most common grade 3 or 4 adverse events in patients treated with axitinib included hypertension (26 [14%] of 189 patients), diarrhoea (17 [9%]), asthenia (16 [8%]), weight decrease (16 [8%]), and PPE (14 [7%]); common grade 3 or 4 adverse events in patients treated with sorafenib included PPE (15 [16%] of 96 patients), diarrhoea (five [5%]), and asthenia (five [5%]). Serious adverse events were reported in 64 (34%) of 189 patients receiving axitinib, and 24 (25%) of 96 patients receiving sorafenib. Interpretation Axitinib did not significantly increase progression-free survival in patients with treatment-naive metastatic renal-cell carcinoma compared with those treated with sorafenib, but did demonstrate clinical activity and an acceptable safety profile. Funding Pfizer Inc.read more
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Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma
Brian I. Rini,Elizabeth R. Plimack,Viktor Stus,Rustem Gafanov,Robert E. Hawkins,Dmitry Nosov,Frédéric Pouliot,Boris Alekseev,Denis Soulières,Bohuslav Melichar,Ihor Vynnychenko,Anna Kryzhanivska,Igor Bondarenko,Sergio J Azevedo,Delphine Borchiellini,Cezary Szczylik,Maurice Markus,Raymond S. McDermott,Jens Bedke,Sophie Tartas,Yen-Hwa Chang,Satoshi Tamada,Qiong Shou,Rodolfo F. Perini,Mei Chen,Michael B. Atkins,Thomas Powles +26 more
TL;DR: Treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression‐free survival, as well as a higher objective response rate, than treatment with sunitin ib among patients with previously untreated advanced renal‐cell carcinoma.
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Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma
Robert J. Motzer,Konstantin Penkov,John B. A. G. Haanen,Brian I. Rini,Laurence Albiges,Matthew T. Campbell,Balaji Venugopal,Christian Kollmannsberger,Sylvie Negrier,Motohide Uemura,Jae L. Lee,Aleksandr Vasiliev,Wilson H. Miller,Howard Gurney,Manuela Schmidinger,James Larkin,Michael B. Atkins,Jens Bedke,Boris Alekseev,Jing Wang,Mariangela Mariani,Paul B. Robbins,Aleksander Chudnovsky,Camilla Fowst,Subramanian Hariharan,Bo Huang,Alessandra di Pietro,Toni K. Choueiri +27 more
TL;DR: Progression‐free survival was significantly longer with avelumab plus axitinib than with sunit inib among patients who received these agents as first‐line treatment for advanced renal‐cell carcinoma.
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Treatment of renal cell carcinoma: Current status and future directions.
Pedro C. Barata,Brian I. Rini +1 more
TL;DR: In the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents as mentioned in this paper.
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Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology
Robert J. Motzer,Eric Jonasch,Neeraj Agarwal,Sam B. Bhayani,William P Bro,Sam S. Chang,Toni K. Choueiri,Brian A. Costello,Ithaar Derweesh,Mayer Fishman,Thomas H. Gallagher,John L. Gore,Steven L. Hancock,Michael R. Harrison,Won Kim,Christos Kyriakopoulos,Chad A. LaGrange,Elaine T. Lam,Clayton Lau,M. Dror Michaelson,Thomas Olencki,Phillip M. Pierorazio,Elizabeth R. Plimack,Bruce G. Redman,Brian Shuch,Brad Somer,Guru Sonpavde,Jeffrey A. Sosman,Mary A. Dwyer,Rashmi Kumar +29 more
TL;DR: The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma.
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Robert J. Motzer,Eric Jonasch,M. Dror Michaelson,Lakshminarayanan Nandagopal,John L. Gore,Saby George,Ajjai Alva,Naomi B. Haas,Michael R. Harrison,Elizabeth R. Plimack,Jeffrey A. Sosman,Neeraj Agarwal,Sam B. Bhayani,Toni K. Choueiri,Brian A. Costello,Ithaar Derweesh,Thomas H. Gallagher,Steven L. Hancock,Christos Kyriakopoulos,Chad A. LaGrange,Elaine T. Lam,Clayton Lau,Bryan Lewis,Brandon Manley,Brittany McCreery,Andrew McDonald,Amir Mortazavi,Phillip M. Pierorazio,Lee Ponsky,Bruce G. Redman,Bradley G. Somer,Geoffrey Wile,Mary A. Dwyer,Lydia J. Hammond,Griselda Zuccarino-Catania +34 more
TL;DR: The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors and desmoid tumors.
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New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
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TL;DR: Progression-free survival was longer and response rates were higher in patients with metastatic renal-cell cancer who received sunitinib than in those receiving interferon alfa.
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Bernard Escudier,Tim Eisen,Walter M. Stadler,Cezary Szczylik,Stéphane Oudard,Michael Siebels,Sylvie Negrier,Christine Chevreau,Ewa Solska,Apurva A. Desai,Frederic Rolland,Tomasz Demkow,Thomas E. Hutson,Martin Gore,Scott Freeman,Brian Schwartz,M. Shan,Ronit Simantov,Ronald M. Bukowski +18 more
TL;DR: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects.
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Gary R. Hudes,Michael A. Carducci,Piotr Tomczak,Janice P. Dutcher,Robert A. Figlin,Anil Kapoor,Elzbieta Staroslawska,Jeffrey A. Sosman,David F. McDermott,Istvan Bodrogi,Zoran Kovacevic,Vladimir Lesovoy,Ingo G.H. Schmidt-Wolf,Olga Barbarash,Erhan Gokmen,Timothy O'Toole,Stephanie Lustgarten,Laurence Moore,Robert J. Motzer +18 more
TL;DR: As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis.
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Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial
Robert J. Motzer,Bernard Escudier,Stéphane Oudard,Thomas E. Hutson,Camillo Porta,Sergio Bracarda,Viktor Grünwald,John A. Thompson,Robert A. Figlin,Norbert Hollaender,Gladys Urbanowitz,William Berg,Andrea Kay,David Lebwohl,Alain Ravaud +14 more
TL;DR: Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies, but were mostly mild or moderate in severity.
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