Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma: Final Overall Survival Analysis of the Phase 3 PROTECT Trial

Motzer, Robert J.; Russo, Paul; Haas, Naomi B.; Doehn, Christian; Donskov, Frede; Gross‐Goupil, Marine; Варламов, Сергей; Kopyltsov, Evgeny; Lee, Jae‐Lyun; Lim, Ho Yeong; Melichar, Bohuslav; Zemanová, Milada; Rini, Brian I.; Choueiri, Toni K.; Wood, Lori; Reaume, M. Neil; Stenzl, Arnulf; McDermott, Ray; Michael, Agnieszka; Izquierdo, M Murillo; Aimone, Paola; Zhang, Hong; Sternberg, Cora N.

doi:10.1016/j.eururo.2020.12.029

Cited by 43 publications

(30 citation statements)

References 9 publications

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“…After careful reading of full-text, 38 studies were further excluded because of the study design and insufficient data presented. Thus, 7 studies met the criteria for inclusion in the present meta-analysis [ 18 – 24 ]. The detailed search process was presented in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

The Efficacy of Adjuvant Targeted Therapy in Patients with Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Yiu

Chen

Zhao

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. The aim of this systematic evaluation and meta-analysis was to analyze the efficacy and adverse effects of adjuvant targeted therapy regimens in advanced or metastatic renal cell carcinoma (RCC). Methods. Studies eligible for the efficacy of adjuvant targeted therapy regimens in advanced or metastatic RCC published before December 2021 in PubMed, Embase, Cochrane Clinical Trials Database (CENTRAL), and Web of Science were searched for (1) patients with locally advanced renal cell carcinoma (RCC) who received adjuvant postoperative targeted therapy versus those not receiving active treatment; (2) primary endpoint outcomes of disease-free survival (DFS), overall survival (OS), and adverse events (AEs); and (3) design: randomized controlled trial (RCT) as inclusion criteria. Data on DFS and OS were extracted or recalculated by meta-analysis as hazard ratios (HRs), and AEs were compared using a dominance ratio (OR). Result. This systematic evaluation will provide evidence on the effectiveness and adverse effects of adjuvant targeted therapy in patients with advanced RCC. The results of meta-analysis showed that all of the three adjuvant targeted therapeutic drugs (sorafenib, sunitinib, and pazopanib) did not benefit from the adjuvant targeted therapy for DFS and OS and even increase the incidence of AEs compared to the placebo. Conclusions. The aim of this study was to summarize data on DFS, OS, and AEs in patients with advanced RCC treated with targeted therapies. The evidence provided by this systematic evaluation and meta-analysis will help guide clinical decision-making and provide insight into the future management of patients with advanced RCC.

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Section: Resultsmentioning

confidence: 99%

The Efficacy of Adjuvant Targeted Therapy in Patients with Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Yiu

Chen

Zhao

et al. 2022

Computational and Mathematical Methods in Medicine

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“…VEGF-targeted tyrosine-kinase inhibitors have shown some efficacy against metastatic renal cell carcinoma, but recent trials of adjuvant therapy with tyrosinekinase inhibitors in this patient population (appendix) have mostly yielded disappointing results. For example, neither sorafenib or sunitinib (in the ASSURE trial), 2 axitinib (in the ATLAS trial), 3 nor pazopanib (in the PROTECT trial) 4 improved disease-free survival or overall survival in renal cell carcinoma. In the randomised, phase 3 S-TRAC study, 5 sunitinib was superior to placebo in improving the primary endpoint of disease-free survival in patients with clear-cell renal cell carcinoma.…”

Section: Adjuvant Immunotherapy For Renal Cell Carcinomamentioning

confidence: 99%

“…The primary endpoint of this trial was progressionfree survival at 12 weeks and patients were ultimately stratified in eight histological cohorts. These commendable choices were undertaken to account for the limited radiological objective responses observed in previous trials 4 and to partly address the intrinsic biological and clinical differences of individual sarcoma subtypes. Overall, progression-free survival at 12 weeks was 49% (95% CI 36-61).…”

Section: Immune Checkpoint Inhibition In Sarcomas: Time To Be Histolo...mentioning

confidence: 99%

Adjuvant immunotherapy for renal cell carcinoma

Şendur

2022

The Lancet Oncology

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“…TKIs targeting the vascular endothelial growth-factor receptor are established in treating metastatic RCC and have been extensively tested in the adjuvant setting. Five TKI trials have produced results: ASSURE, PROTECT, S-TRAC, ATLAS and now SORCE [ [5] , [6] , [7] , [8] , [9] , [10] ]. These studies evaluated the effect of oral TKIs compared to placebo and none have shown a benefit of TKI on overall survival (OS) [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Five TKI trials have produced results: ASSURE, PROTECT, S-TRAC, ATLAS and now SORCE [ [5] , [6] , [7] , [8] , [9] , [10] ]. These studies evaluated the effect of oral TKIs compared to placebo and none have shown a benefit of TKI on overall survival (OS) [ 10 , 11 ]. Only the S-TRAC trial showed a modest DFS benefit with 1 year of sunitinib (HR 0.76; 95% CI 0.59–0.98; p = 0.03) compared to placebo on blinded independent central review [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

RAMPART: A phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse

Oza

Frangou

Smith

et al. 2021

Contemporary Clinical Trials

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Background 20–60% of patients with initially locally advanced Renal Cell Carcinoma (RCC) develop metastatic disease despite optimal surgical excision. Adjuvant strategies have been tested in RCC including cytokines, radiotherapy, hormones and oral tyrosine-kinase inhibitors (TKIs), with limited success. The predominant global standard-of-care after nephrectomy remains active monitoring. Immune checkpoint inhibitors (ICIs) are effective in the treatment of metastatic RCC; RAMPART will investigate these agents in the adjuvant setting. Methods/design RAMPART is an international, UK-led trial investigating the addition of ICIs after nephrectomy in patients with resected locally advanced RCC. RAMPART is a multi-arm multi-stage (MAMS) platform trial, upon which additional research questions may be addressed over time. The target population is patients with histologically proven resected locally advanced RCC (clear cell and non-clear cell histological subtypes), with no residual macroscopic disease, who are at high or intermediate risk of relapse (Leibovich score 3–11). Patients with fully resected synchronous ipsilateral adrenal metastases are included. Participants are randomly assigned (3,2:2) to Arm A - active monitoring (no placebo) for one year, Arm B - durvalumab (PD-L1 inhibitor) 4-weekly for one year; or Arm C - combination therapy with durvalumab 4-weekly for one year plus two doses of tremelimumab (CTLA-4 inhibitor) at day 1 of the first two 4-weekly cycles. The co-primary outcomes are disease-free-survival (DFS) and overall survival (OS). Secondary outcomes include safety, metastasis-free survival, RCC specific survival, quality of life, and patient and clinician preferences. Tumour tissue, plasma and urine are collected for molecular analysis (TransRAMPART). Trial registration ISRCTN #: ISRCTN53348826, NCT #: NCT03288532 , EUDRACT #: 2017–002329-39, CTA #: 20363/0380/001–0001, MREC #: 17/LO/1875, ClinicalTrials.gov Identifier: NCT03288532 , RAMPART grant number: MC_UU_12023/25, TransRAMPART grant number: A28690 Cancer Research UK, RAMPART Protocol version 5.0.

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Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma: Final Overall Survival Analysis of the Phase 3 PROTECT Trial

Cited by 43 publications

References 9 publications

The Efficacy of Adjuvant Targeted Therapy in Patients with Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

The Efficacy of Adjuvant Targeted Therapy in Patients with Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Adjuvant immunotherapy for renal cell carcinoma

RAMPART: A phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse

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