TY - JOUR
T1 - Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib
T2 - ESMO 2017 Congress - European Society for Medical Oncology
AU - Bex, Axel
AU - Mulders, Peter
AU - Jewett, Michael
AU - Wagstaff, John
AU - van Thienen, Johannes V.
AU - Blank, Christian U.
AU - van Velthoven, Roland
AU - Laguna, Maria del Pilar
AU - Wood, Lori
AU - van Melick, Harm H. E.
AU - Aarts, Maureen J.
AU - Lattouf, J. B.
AU - Powles, Thomas
AU - de Jong, Igle Jan
AU - Rottey, Sylvie
AU - Tombal, Bertrand
AU - Marreaud, Sandrine
AU - Collette, Sandra
AU - Collette, Laurence
AU - Haanen, John
N1 - Funding Information:
Pfizer and Kankerbestrijding/KWF from the Netherlands through the Cancer Cancer Research Fund of the European Organisation for Research and Treatment of Cancer. Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
Funding/Support: This study was supported by
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2019/2
Y1 - 2019/2
N2 - IMPORTANCE In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown.OBJECTIVE To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied.INTERVENTIONS Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy.MAIN OUTCOMES AND MEASURES Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points.RESULTS The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%).CONCLUSIONS AND RELEVANCE Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib.
AB - IMPORTANCE In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown.OBJECTIVE To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied.INTERVENTIONS Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy.MAIN OUTCOMES AND MEASURES Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points.RESULTS The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%).CONCLUSIONS AND RELEVANCE Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib.
KW - PLANNED NEPHRECTOMY
KW - TARGETED THERAPY
KW - RADICAL NEPHRECTOMY
KW - INTERFERON-ALPHA
KW - CANCER
KW - SURVIVAL
KW - MORBIDITY
KW - MORTALITY
KW - RESECTION
KW - EFFICACY
U2 - 10.1001/jamaoncol.2018.5543
DO - 10.1001/jamaoncol.2018.5543
M3 - Article
C2 - 30543350
SN - 2374-2437
VL - 5
SP - 164
EP - 170
JO - JAMA Oncology
JF - JAMA Oncology
IS - 2
Y2 - 8 September 2017 through 12 September 2017
ER -