marzo 2019

Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial

Cella D, Grünwald V, Escudier B, et al.
Lancet Oncol. 2018. January 15, 2019
DOI: 10.1016/S1470-2045(18)30778-2

Abstract

BACKGROUND:

In the ongoing phase 3, CheckMate 214 trial, nivolumab plus ipilimumab improved overall survival compared with sunitinib in patients with intermediate or poor risk, previously untreated, advanced renal cell carcinoma. We aimed to assess whether health-related quality of life (HRQoL) could be used to further describe the benefit-risk profile of nivolumab plus ipilimumab versus sunitinib.

METHODS:

In the phase 3, randomised, controlled, CheckMate 214 trial, patients aged 18 years and older with previously untreated, advanced or metastatic renal cell carcinoma with a clear-cell component were recruited from 175 hospitals and cancer centres in 28 countries. Patients were categorised by risk status into favourable, intermediate, and poor risk subgroups and randomly assigned (1:1) to open-label nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg/day for 4 weeks of each 6-week cycle. Randomisation was done with a block size of four and stratified by risk status and geographical region. Patient-reported outcomes (PROs) were assessed using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), Functional Assessment of Cancer Therapy-General (FACT-G), and EuroQol five dimensional three level (EQ-5D-3L) instruments. The coprimary endpoints of the trial, reported previously, were overall survival, progression-free survival, and the proportion of patients who had an objective response in those categorised as at intermediate or poor risk. PROs in all randomised participants were assessed as an exploratory endpoint; here we report this exploratory endpoint. This study is registered with ClinicalTrials.gov, number NCT02231749, and is ongoing but is now closed to recruitment.

FINDINGS:

Between Oct 16, 2014, and Feb 23, 2016, of 1390 patients screened, 1096 (79%) were randomly assigned to treatment, of whom 847 (77%) were at intermediate or poor risk and randomly assigned to nivolumab plus ipilimumab (n=425) or sunitinib (n=422). Median follow-up was 25·2 months (IQR 23·0–27·4). PROs were more favourable with nivolumab plus ipilimumab than sunitinib throughout the first 103 weeks after baseline, with mean change from baseline at week 103 for FKSI-19 total score being 4·00 (95% CI 1·91 to 6·09) for nivolumab plus ipilimumab versus −3·14 (−6·03 to −0·25) for sunitinib (p<0·0001), and for FACT-G total score being 4·77 (1·73 to 7·82) for nivolumab plus ipilimumab versus −4·32 (−8·54 to −0·11) for sunitinib (p=0·0005). Significant differences were also seen for four of five FKSI-19 domains (disease-related symptoms, physical disease-related symptoms, treatment side-effects, and functional wellbeing) and FACT-G physical and functional wellbeing domains. However, there was no significant difference between the treatment groups at week 103 in EQ-5D-3L visual analogue rating scale (VAS) scores, with mean change from baseline to week 103 of 10·07 (95% CI 4·35 to 15·80) for nivolumab plus ipilimumab and 6·40 (−1·36 to 14·16) for sunitinib (p=0·45). Compared with sunitinib, nivolumab plus ipilimumab reduced risk of deterioration in FKSI-19 total score (hazard ratio [HR] 0·54; 95% CI 0·46–0·63), FACT-G total score (0·63, 0·52–0·75), and EQ-5D-3L VAS score (HR 0·75, 95% CI 0·63–0·89) and UK utility scores (0·67, 0·57–0·80).

INTERPRETATION:

Nivolumab plus ipilimumab leads to fewer symptoms and better HRQoL than sunitinib in patients at intermediate or poor risk with advanced renal cell carcinoma. These results suggest that the superior efficacy of nivolumab plus ipilimumab over sunitinib comes with the additional benefit of improved HRQoL.

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The creation, development and diffusion of the LARCG – Latin American Renal Cancer Group

Stênio de Cássio Zequi, Diego Abreu Clavijo and all other LARCG Members.
IBJU Vol. 43 (1): 3-6, January – February, 2017
DOI: 10.1590/S1677-5538.IBJU.2017.01.02

Introduction

As usually verified in many malignancies, the majority of the scientific information about renal cell carcinoma (RCC) is produced in developed countries mainly in North America and Europe. This knowledge is derived from great casuistries, joined in multi-institutional collaborative study groups or in International dise- ases consortiums.

Consistent epidemiologic and scientific data originated in the Latin America (LA) are lacking. LA is a large subcontinent, composed by more than 20 countries (much of them great economies), encompassing around 640 million habitants. Latin American population ethnicity is unique, due to an intense miscegenation, differing from northern hemispheric populations. The LA’s population was composed by several civilizations over the years: pre Colombians, (Amerindians), black slaves descendant’s (distinct groups of the African slaves that were sent to North America and Caribe). The predominance of Europeans in LA corresponded to Iberians, and Italians, few French and Germans. We have few Anglo-Saxon, Scandinavian and Northern and Eas- tern Europeans. Regarding Middle East and Africans, the more prevalent immigrants were Syrian, Lebaneses, Jewishs and few Armenians. Also, there are few Arabic, Persian and North African populations. From Asia, the predominance has been established by Japanese and in the last decades, by some Korean and Chinese. There is almost no people from South Asia, Oceania and Pacific Islands etc., differing from US, for example. The LA racial miscegenation resulted in particular genetic groups such as Mulattoes, Mestizos, Zambos, Cimarron’s, Cafuzzos, mamelucos etc.

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Functional and oncologic outcomes after nephron-sparing surgery in a solitary kidney: 10 years of experience

José Ignacio Costabel, Patricio García Marchiñena, Federico Tirapegui, Augusto Dantur, Alberto Jurado, Guillermo Gueglio.
Departamento de Urología del Hospital Italiano de Buenos Aires, Argentina.
Int Braz J urol. 2016; 42: 253-61

Abstract

Objectives:

To evaluate functional and oncologic outcomes of partial nephrectomy (PN) in patients with a solitary kidney.

MATERIALS AND METHODS:

A retrospective analysis of patients with a solitary kidney undergoing nephron-sparing surgery between March 2003 and March 2013 was performed. GFR was recorded before the procedure and 3 months after surgery, thus establishing a change (cGFR). Several variables that may influence cGFR were analyzed. Complications are herein described, namely bleeding, fistula, acute renal failure and end-stage renal disease (ESRD). Local recurrence and margin status are also described. Survival rates were calculated using the Kaplan Meier method (2 patients with metastasis at the time of surgery were excluded from the analysis).

RESULTS:

Forty-five patients were available for analysis. Median follow-up was 27.56 months (r 3-96). Mean cGFR was-7.12mL/min (SD 2.1). Variables significantly related with lower GFR after surgery were loss of renal mass (p=0.01)) and male gender (p=0.03). Four patients (8.8%) experienced hemorrhage. Nine patients (20%) developed a urinary fistula. Only one patient with bleeding required open surgery. Two patients (4.4%) needed transient dialysis. Three patients (6.6%) developed ESRD. Four patients (8.8%) had positive surgical margins (PSMs) and four patients (88%) had local recurrence (2 of these had PSMs). Five patients (11.1%) died during follow-up. Four patients (8.8%) died because of renal cancer. Estimated 2-year overall survival, disease-free survival and cancer specific survival rates were 88.4% (CI 95% 70.5-96); 87.7% (CI 95% 68.1-96) and 92.4% (CI 95% 75-98), respectively.

CONCLUSIONS:

Loss of renal mass and male gender were associated with lower postoperative GFR. Our outcomes were comparable with those in the World literature.

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