Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long‐term follow‐up of the randomized, open‐label, phase 3 CheckMate 025 trial
Background CheckMate 025 has shown superior efficacy for nivolumab over everolimus in patients with advanced renal cell carcinoma (aRCC) along with improved safety and tolerability. This analysis assesses the long‐term clinical benefits of nivolumab versus everolimus. Methods The randomized, open‐la...
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| Vydáno v: | Cancer Ročník 126; číslo 18; s. 4156 - 4167 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
Wiley Subscription Services, Inc
15.09.2020
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| Témata: | |
| ISSN: | 0008-543X, 1097-0142, 1097-0142 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | Background
CheckMate 025 has shown superior efficacy for nivolumab over everolimus in patients with advanced renal cell carcinoma (aRCC) along with improved safety and tolerability. This analysis assesses the long‐term clinical benefits of nivolumab versus everolimus.
Methods
The randomized, open‐label, phase 3 CheckMate 025 trial (NCT01668784) included patients with clear cell aRCC previously treated with 1 or 2 antiangiogenic regimens. Patients were randomized to nivolumab (3 mg/kg every 2 weeks) or everolimus (10 mg once a day) until progression or unacceptable toxicity. The primary endpoint was overall survival (OS). The secondary endpoints were the confirmed objective response rate (ORR), progression‐free survival (PFS), safety, and health‐related quality of life (HRQOL).
Results
Eight hundred twenty‐one patients were randomized to nivolumab (n = 410) or everolimus (n = 411); 803 patients were treated (406 with nivolumab and 397 with everolimus). With a minimum follow‐up of 64 months (median, 72 months), nivolumab maintained an OS benefit in comparison with everolimus (median, 25.8 months [95% CI, 22.2‐29.8 months] vs 19.7 months [95% CI, 17.6‐22.1 months]; hazard ratio [HR], 0.73; 95% CI, 0.62‐0.85) with 5‐year OS probabilities of 26% and 18%, respectively. ORR was higher with nivolumab (94 of 410 [23%] vs 17 of 411 [4%]; P < .001). PFS also favored nivolumab (HR, 0.84; 95% CI, 0.72‐0.99; P = .0331). The most common treatment‐related adverse events of any grade were fatigue (34.7%) and pruritus (15.5%) with nivolumab and fatigue (34.5%) and stomatitis (29.5%) with everolimus. HRQOL improved from baseline with nivolumab but remained the same or deteriorated with everolimus.
Conclusions
The superior efficacy of nivolumab over everolimus is maintained after extended follow‐up with no new safety signals, and this supports the long‐term benefits of nivolumab monotherapy in patients with previously treated aRCC.
LAY SUMMARY
CheckMate 025 compared the effects of nivolumab (a novel immunotherapy) with those of everolimus (an older standard‐of‐care therapy) for the treatment of advanced kidney cancer in patients who had progressed on antiangiogenic therapy.
After 5 years of study, nivolumab continues to be better than everolimus in extending the lives of patients, providing a long‐lasting response to treatment, and improving quality of life with a manageable safety profile. The results demonstrate that the clinical benefits of nivolumab versus everolimus in previously treated patients with advanced kidney cancer continue in the long term.
The results of the 5‐year follow‐up analysis of the CheckMate 025 trial demonstrate that the clinical benefits are sustained with nivolumab over everolimus in previously treated patients with advanced renal cell carcinoma in the long term. Overall survival, progression‐free survival, and objective response rate benefits are maintained with nivolumab versus everolimus, and more patients treated with nivolumab experience improved health‐related quality of life; meanwhile, the safety of nivolumab is manageable and compares favorably with that of everolimus. |
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| Bibliografie: | We thank the patients and their families as well as the investigators and participating clinical study teams for making this study possible. We also thank Elmer Berghorn for his contributions to the study; Dako (an Agilent Technologies, Inc, company) for collaborative development of the PD‐L1 IHC 28‐8 pharmDx assay; and Bristol‐Myers Squibb Company (Princeton, New Jersey) and ONO Pharmaceutical Company, Ltd (Osaka, Japan). Professional medical writing and editorial assistance was provided by Jenny Reinhold, PharmD (Parexel), and was funded by Bristol‐Myers Squibb Company. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 AUTHOR CONTRIBUTIONS Robert J. Motzer: conceptualization, investigation, validation, writing – review and editing. Bernard Escudier: investigation, validation, writing – review and editing. Saby George: investigation, validation, writing – review and editing. Hans J. Hammers: investigation, validation, writing – review and editing. Sandhya Srinivas: investigation, validation, writing – review and editing. Scott S. Tykodi: investigation, validation, writing – review and editing. Jeffrey A. Sosman: investigation, validation, writing – review and editing. Elizabeth R. Plimack, MD: investigation, validation, writing – review and editing. Giuseppe Procopio, MD: investigation, validation, writing – review and editing. David F. McDermott, MD: investigation, validation, writing – review and editing. Daniel Castellano: investigation, validation, writing – review and editing. Toni K. Choueiri: investigation, validation, writing – review and editing. Frede Donskov: investigation, validation, writing – review and editing. Howard Gurney: investigation, validation, writing – review and editing. Stéphane Oudard: investigation, validation, writing – review and editing. Martin Richardet: investigation, validation, writing – review and editing. Katriina Peltola: investigation, validation, writing – review and editing. Ajjai S. Alva: investigation, validation, writing – review and editing. Michael A. Carducci: investigation, validation, writing – review and editing. John Wagstaff: investigation, validation, writing – review and editing. Christine Chevreau: investigation, validation, writing – review and editing. Satoshi Fukasawa: investigation, validation, writing – review and editing. Yoshihiko Tomita: investigation, validation, writing – review and editing. Thomas C. Gauler: investigation, validation, writing – review and editing. Christian K. Kollmannsberger: investigation, validation, writing – review and editing. Fabio A. Schutz: investigation, validation, writing – review and editing. James M. Larkin: investigation, validation, writing – review and editing. David Cella: investigation, validation, writing – review and editing. M. Brent McHenry: conceptualization, data curation, formal analysis, methodology, project administration, resources, software, supervision, validation”.. Shruti Shally Saggi: conceptualization, data curation, formal analysis, methodology, project administration, resources, software, supervision, validation”.. Nizar M. Tannir: conceptualization, investigation, validation, writing – review and editing.. |
| ISSN: | 0008-543X 1097-0142 1097-0142 |
| DOI: | 10.1002/cncr.33033 |