BACKGROUND: Non-clear cell renal cell cancers (nccRCCs) are a heterogeneous group of more than 20 different entities, but are rarely included in large, randomized trials. Tyrosine kinase inhibitors with or without immune checkpoint inhibition are considered as a standard of care (SOC), but optimal treatment is not yet defined. We designed the first prospective randomized trial comparing ipilimumab/nivolumab to SOC. PATIENTS AND METHODS: We randomized adult patients with previously untreated advanced or metastatic nccRCC 1:1 to nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by fixed dose nivolumab of 240 mg every 2 weeks or 480 mg every 4 weeks or to SOC. Patients were stratified by histology and by IMDC risk score. Central pathology review was mandatory. The primary endpoint was the overall survival (OS) rate at 12 months, secondary endpoints included median OS, response rate, progression-free survival (PFS), safety and quality of life. RESULTS: In total, 157 patients were assigned to receive ipilimumab/nivolumab, and 152 to SOC. The 12-month survival rate was 78% with ipilimumab/nivolumab [95% confidence interval (CI) 71-84%] compared to 68% with SOC (95% CI 60-75%, P = 0.026). Median OS was 33.2 months versus 25.2 months, P = 0.163 [HR 0.81 (0.61-1.099)]. PFS was similar in both arms [HR 0.99 (0.77-1.28)]. The ORR was 32.8% versus 19.3%. No major differences between papillary and non-papillary RCC subtypes were observed for any endpoint. Exploratory analysis showed a significant OS advantage [HR 0.56 (95% CI 0.37-0.86)] associated with a PD-L1 CPS score ≥1. Treatment discontinuation due to toxicity occurred in 27 patients (17%) with ipilimumab/nivolumab and 13 patients (9%) with SOC. CONCLUSIONS: Ipilimumab/nivolumab demonstrated a significantly longer OS at the 12-month milestone and an acceptable toxicity profile. Our results therefore underline a relevant clinical benefit of ipilimumab/nivolumab in previously untreated nccRCC entities compared to current SOC.
- MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- ipilimumab * aplikace a dávkování škodlivé účinky MeSH
- karcinom z renálních buněk * farmakoterapie patologie mortalita MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie patologie mortalita MeSH
- nivolumab * aplikace a dávkování škodlivé účinky MeSH
- prospektivní studie MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- standardní péče MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
- MeSH
- delfská metoda MeSH
- konsensus * MeSH
- lékařská onkologie metody normy MeSH
- lidé MeSH
- mezinárodní spolupráce MeSH
- močový měchýř patologie MeSH
- nádory močového měchýře patologie terapie MeSH
- průzkumy a dotazníky MeSH
- směrnice pro lékařskou praxi jako téma * MeSH
- společnosti lékařské normy MeSH
- staging nádorů MeSH
- účast zainteresovaných stran MeSH
- urologie metody normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Münchener medizinische Wochenschrift, ISSN 0341-3098 Sondernummer Jhr. 133. 30
S64 s. : il. ; 28 cm
Acta neurologica Scandinavica, ISSN 0065-1427 suppl. no. 127, vol. 80, 1989
48 s. : il., tab., grafy ; 24 cm
Fortschritte der Medizin, ISSN 0932-5611 Jahrgang 103, Suppl. 8, 1985
19 s. : il., tab., grafy ; 28 cm
- MeSH
- blokátory kalciových kanálů MeSH
- cerebrovaskulární poruchy MeSH
- farmakoterapie MeSH
- Publikační typ
- kongresy MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- neurovědy
- farmacie a farmakologie
- neurologie
176 s. : il.
