Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu klinické zkoušky, fáze III, časopisecké články, randomizované kontrolované studie, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P30 CA008748
NCI NIH HHS - United States
P30 CA016672
NCI NIH HHS - United States
PubMed
32661118
PubMed Central
PMC7359377
DOI
10.1136/jitc-2020-000891
PII: jitc-2020-000891
Knihovny.cz E-zdroje
- Klíčová slova
- CTLA-4 antigen, clinical trials, phase III as topic, immunotherapy, kidney neoplasms, programmed cell death 1 receptor,
- MeSH
- analýza přežití MeSH
- ipilimumab farmakologie terapeutické užití MeSH
- karcinom z renálních buněk farmakoterapie mortalita patologie MeSH
- lidé MeSH
- nádory ledvin farmakoterapie mortalita patologie MeSH
- následné studie MeSH
- nivolumab farmakologie terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie farmakologie terapeutické užití MeSH
- sunitinib farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- ipilimumab MeSH
- nivolumab MeSH
- sunitinib MeSH
BACKGROUND: The extent to which response and survival benefits with immunotherapy-based regimens persist informs optimal first-line treatment options. We provide long-term follow-up in patients with advanced renal cell carcinoma (aRCC) receiving first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the phase 3 CheckMate 214 trial. Survival, response, and safety outcomes with NIVO+IPI versus SUN were assessed after a minimum of 42 months of follow-up. METHODS: Patients with aRCC were enrolled from October 16, 2014, through February 23, 2016. Patients stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and region were randomized to 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 SUN (50 mg) once per day for 4 weeks (6-week cycle). Primary endpoints: overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) per independent radiology review committee in IMDC intermediate-risk/poor-risk patients. Secondary endpoints: OS, PFS, and ORR in the intention-to-treat (ITT) population and safety. Favorable-risk patient outcomes were exploratory. RESULTS: Among ITT patients, 550 were randomized to NIVO+IPI (425 intermediate/poor risk; 125 favorable risk) and 546 to SUN (422 intermediate/poor risk; 124 favorable risk). Among intermediate-risk/poor-risk patients, OS (HR, 0.66; 95% CI, 0.55-0.80) and PFS (HR, 0.75; 95% CI, 0.62-0.90) benefits were observed, and ORR was higher (42.1% vs 26.3%) with NIVO+IPI versus SUN. In ITT patients, both OS benefits (HR, 0.72; 95% CI, 0.61-0.86) and higher ORR (39.1% vs 32.6%) were observed with NIVO+IPI versus SUN. In favorable-risk patients, HR for death was 1.19 (95% CI, 0.77-1.85) and ORR was 28.8% with NIVO+IPI versus 54.0% with SUN. Duration of response was longer (HR, 0.46-0.54), and more patients achieved complete response (10.1%-12.8% vs 1.4%-5.6%) with NIVO+IPI versus SUN regardless of risk group. The incidence of treatment-related adverse events was consistent with previous reports. CONCLUSIONS: NIVO+IPI led to improved efficacy outcomes versus SUN in both intermediate-risk/poor-risk and ITT patients that were maintained through 42 months' minimum follow-up. A complete response rate >10% was achieved with NIVO+IPI regardless of risk category, with no new safety signals detected in either arm. These results support NIVO+IPI as a first-line treatment option with the potential for durable response. TRIAL REGISTRATION NUMBER: NCT02231749.
Bristol Myers Squibb Princeton New Jersey USA
Centro de Investigación Clínica Bradford Hill Santiago Chile
Clinic for Medical Oncology and Clinic for Urology Essen University Hospital Essen Germany
Clinical Research Division Fred Hutchinson Cancer Research Center Seattle Washington USA
Davidoff Cancer Center Rabin Medical Center Petah Tikva Israel
Department of Hematology and Oncology Cleveland Clinic Taussig Cancer Institute Cleveland Ohio USA
Department of Hematology Oncology Fox Chase Cancer Center Philadelphia Pennsylvania USA
Department of Internal Medicine University of Pavia Pavia Italy
Department of Medical Oncology Bordeaux University Hospital Bordeaux France
Department of Medical Oncology Gustave Roussy Villejuif France
Department of Medical Oncology Hôpitaux Universitaires de Strasbourg ICANS Strasbourg France
Department of Medical Oncology Levine Cancer Institute Atrium Health Charlotte North Carolina USA
Department of Medical Oncology Westmead Hospital Sydney New South Wales Australia
Department of Medicine Division of Medical Oncology University of Washington Seattle Washington USA
Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA
Department of Oncology Aarhus University Hospital Aarhus Denmark
Department of Oncology Herlev Hospital Copenhagen Denmark
Department of Oncology Palacky University and University Hospital Olomouc Olomouc Czech Republic
Department of Urology Jena University Hospital Jena Germany
Division of Hematology and Oncology UT Southwestern Kidney Cancer Program Dallas Texas USA
Division of Medical Oncology British Columbia Cancer Agency Vancouver British Columbia Canada
Instituto Oncológico Fundación Arturo López Pérez Santiago Chile
Interdisciplinary Genitourinary Oncology West German Cancer Center Essen Essen Germany
Oncology Institute Shamir Medical Center Be'er Yaakov Israel
Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
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Rini BI, Battle D, Figlin RA, et al. . The Society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC). J Immunother Cancer 2019;7. 10.1186/s40425-019-0813-8 PubMed DOI PMC
Atkins MB, Tannir NM. Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma. Cancer Treat Rev 2018;70:127–37. 10.1016/j.ctrv.2018.07.009 PubMed DOI
Motzer RJ, Tannir NM, McDermott DF, et al. . Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018;378:1277–90. 10.1056/NEJMoa1712126 PubMed DOI PMC
Rini BI, Plimack ER, Stus V, et al. . Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019;380:1116–27. 10.1056/NEJMoa1816714 PubMed DOI
Motzer RJ, Tykodi SS, Escudier B, et al. . Long-Term follow-up of nivolumab versus everolimus in patients with advanced renal cell carcinoma: the phase 3 CheckMate 025 trial. Presented at: 18th International Kidney Cancer Symposium (IKCS), Miami, FL, USA, 2019. PubMed PMC
Jonasch E. Updates to the management of kidney cancer. J Natl Compr Canc Netw 2018;16:639–41. 10.6004/jnccn.2018.0039 PubMed DOI
Calvo E, Porta C, Grünwald V, et al. . The current and evolving landscape of first-line treatments for advanced renal cell carcinoma. Oncologist 2019;24:338–48. 10.1634/theoncologist.2018-0267 PubMed DOI PMC
Motzer RJ, Rini BI, McDermott DF, et al. . Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol 2019;20:1370–85. 10.1016/S1470-2045(19)30413-9 PubMed DOI PMC
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81. 10.1080/01621459.1958.10501452 DOI
Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 1934;26:404–13. 10.1093/biomet/26.4.404 DOI
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–88. 10.1016/0197-2456(86)90046-2 PubMed DOI
Rao D, Butt Z, Rosenbloom S, et al. . A comparison of the Renal Cell Carcinoma-Symptom index (RCC-SI) and the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI). J Pain Symptom Manage 2009;38:291–8. 10.1016/j.jpainsymman.2008.08.013 PubMed DOI PMC
Rothrock NE, Jensen SE, Beaumont JL, et al. . Development and initial validation of the NCCN/FACT symptom index for advanced kidney cancer. Value Health 2013;16:789–96. 10.1016/j.jval.2013.04.015 PubMed DOI PMC
Masuda K, Shoji H, Nagashima K, et al. . Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab. BMC Cancer 2019;19:974. 10.1186/s12885-019-6150-y PubMed DOI PMC
Haratani K, Hayashi H, Chiba Y, et al. . Association of immune-related adverse events with nivolumab efficacy in non-small-cell lung cancer. JAMA Oncol 2018;4:374–8. 10.1001/jamaoncol.2017.2925 PubMed DOI PMC
Toi Y, Sugawara S, Kawashima Y, et al. . Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. Oncologist 2018;23:1358–65. 10.1634/theoncologist.2017-0384 PubMed DOI PMC
Sanlorenzo M, Vujic I, Daud A, et al. . Pembrolizumab cutaneous adverse events and their association with disease progression. JAMA Dermatol 2015;151:1206–12. 10.1001/jamadermatol.2015.1916 PubMed DOI PMC
The Evolving Landscape of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma
ClinicalTrials.gov
NCT02231749
