M Dror Michaelson1, Rana R McKay2, Lillian Werner3, Michael B Atkins4, Eliezer M Van Allen2, Kara M Olivier1, Jiaxi Song5, Sabina Signoretti5, David F McDermott6, Toni K Choueiri2. 1. Massachusetts General Hospital Cancer Center, Boston, Massachusetts. 2. Kidney Cancer Center, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. 4. Department of Medical Oncology, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC. 5. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. 6. Department of Medical Oncology, Beth-Israel Deaconess Medical Center, Boston, Massachusetts.
Abstract
BACKGROUND: Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC. METHODS: This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives. RESULTS: Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had >10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with ≤10% sarcomatoid histology (P = .04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7). CONCLUSIONS: These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation.
BACKGROUND:Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC. METHODS: This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives. RESULTS: Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had >10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with ≤10% sarcomatoid histology (P = .04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7). CONCLUSIONS: These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation.
Authors: Cedric Lebacle; Aydin Pooli; Thomas Bessede; Jacques Irani; Allan J Pantuck; Alexandra Drakaki Journal: World J Urol Date: 2018-06-01 Impact factor: 4.226
Authors: Simon Chowdhury; Marc R Matrana; Christopher Tsang; Bradley Atkinson; Toni K Choueiri; Nizar M Tannir Journal: Hematol Oncol Clin North Am Date: 2011-08 Impact factor: 3.722
Authors: Yasser Ged; Ying-Bei Chen; Andrea Knezevic; Jozefina Casuscelli; Almedina Redzematovic; Renzo G DiNatale; Maria I Carlo; Chung-Han Lee; Darren R Feldman; Sujata Patil; A Ari Hakimi; Paul Russo; Robert J Motzer; Martin H Voss Journal: Clin Genitourin Cancer Date: 2019-04-01 Impact factor: 2.872
Authors: Sebastien J Hotte; Anil Kapoor; Naveen S Basappa; Georg Bjarnason; Christina Canil; Henry J Conter; Piotr Czaykowski; Jeffrey Graham; Samantha Gray; Daniel Y C Heng; Pierre I Karakiewicz; Christian Kollmannsberger; Aly-Khan A Lalani; Scott A North; François Patenaude; Denis Soulières; Phillippe Violette; Eric Winquist; Lori A Wood; Shaan Dudani; Ranjena Maloni; M Neil Reaume Journal: Can Urol Assoc J Date: 2019-10 Impact factor: 1.862
Authors: Abhishek Maiti; Maryam Nemati-Shafaee; Pavlos Msaouel; Lance C Pagliaro; Eric Jonasch; Nizar M Tannir; Amishi Y Shah Journal: Clin Genitourin Cancer Date: 2017-08-10 Impact factor: 2.872
Authors: M Neil Reaume; Naveen S Basappa; Lori Wood; Anil Kapoor; Georg A Bjarnason; Normand Blais; Rodney H Breau; Christina Canil; Patrick Cheung; Henry J Conter; Sebastien J Hotte; Claudio Jeldres; Michael A S Jewett; Pierre I Karakiewicz; Christian Kollmannsberger; Francois Patenaude; Alan So; Denis Soulières; Peter Venner; Phillippe Violette; Pawel Zalewski; Heather Chappell; Scott A North Journal: Can Urol Assoc J Date: 2017-10 Impact factor: 1.862