Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study
- PMID: 28678668
- PMCID: PMC7587408
- DOI: 10.1200/JCO.2016.72.1985
Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study
Abstract
Purpose Combination treatment with immune checkpoint inhibitors has shown enhanced antitumor activity compared with monotherapy in tumor types such as melanoma. The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab plus ipilimumab in combination, and nivolumab plus a tyrosine kinase inhibitor in metastatic renal cell carcinoma (mRCC). Safety and efficacy results from the nivolumab plus ipilimumab arms of the study are presented. Patients and Methods Patients with mRCC received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3) every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks until progression or toxicity. End points included safety (primary), objective response rate, and overall survival (OS). Results All patients in the N3I3 arm (n = 6) were censored at the time of analysis as a result of dose-limiting toxicity or other reasons. Forty-seven patients were treated in both the N3I1 and the N1I3 arm, and baseline patient characteristics were balanced between arms. Grade 3 to 4 treatment-related adverse events were reported in 38.3% and 61.7% of the patients in the N3I1 and N1I3 arms, respectively. At a median follow-up of 22.3 months, the confirmed objective response rate was 40.4% in both arms, with ongoing responses in 42.1% and 36.8% of patients in the N3I1 and N1I3 arms, respectively. The 2-year OS was 67.3% and 69.6% in the N3I1 and N1I3 arms, respectively. Conclusion Nivolumab plus ipilimumab therapy demonstrated manageable safety, notable antitumor activity, and durable responses with promising OS in patients with mRCC.
Figures
![Fig 1.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7299/7587408/d4cf31d96cde/JCO.2016.72.1985f1.gif)
![Fig 2.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7299/7587408/b035f382af90/JCO.2016.72.1985f2.gif)
![Fig 3.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7299/7587408/3751dafcdd1f/JCO.2016.72.1985f3.gif)
![Fig A1.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7299/7587408/25def7fbe1ff/JCO.2016.72.1985app1.gif)
![Fig A2.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7299/7587408/15b09d2b3eea/JCO.2016.72.1985app2.gif)
![Fig A3.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7299/7587408/241bf6983808/JCO.2016.72.1985app3.gif)
Similar articles
-
Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma.N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21. N Engl J Med. 2018. PMID: 29562145 Free PMC article. Clinical Trial.
-
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 Oct;20(10):1370-1385. doi: 10.1016/S1470-2045(19)30413-9. Epub 2019 Aug 16. Lancet Oncol. 2019. PMID: 31427204 Free PMC article. Clinical Trial.
-
Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study.J Immunother Cancer. 2018 Oct 22;6(1):109. doi: 10.1186/s40425-018-0420-0. J Immunother Cancer. 2018. PMID: 30348216 Free PMC article. Clinical Trial.
-
The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis.World J Surg Oncol. 2020 Jul 3;18(1):150. doi: 10.1186/s12957-020-01933-5. World J Surg Oncol. 2020. PMID: 32620130 Free PMC article. Review.
-
Ipilimumab in combination with nivolumab for the treatment of renal cell carcinoma.Expert Opin Biol Ther. 2018 Sep;18(9):947-957. doi: 10.1080/14712598.2018.1513485. Epub 2018 Aug 30. Expert Opin Biol Ther. 2018. PMID: 30124333 Free PMC article. Review.
Cited by
-
Checkpoint modulation--A new way to direct the immune system against renal cell carcinoma.Hum Vaccin Immunother. 2015;11(5):1201-8. doi: 10.1080/21645515.2015.1016657. Hum Vaccin Immunother. 2015. PMID: 25912622 Free PMC article. Review.
-
Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma.World J Gastroenterol. 2016 Sep 7;22(33):7440-52. doi: 10.3748/wjg.v22.i33.7440. World J Gastroenterol. 2016. PMID: 27672267 Free PMC article. Review.
-
Checkpoint inhibitors and other novel immunotherapies for advanced renal cell carcinoma.Nat Rev Urol. 2016 Jul;13(7):420-31. doi: 10.1038/nrurol.2016.103. Epub 2016 Jun 21. Nat Rev Urol. 2016. PMID: 27324121 Free PMC article. Review.
-
Programmed Death Ligand 1 Indicates Pre-Existing Adaptive Immune Response by Tumor-Infiltrating CD8+ T Cells in Non-Small Cell Lung Cancer.Int J Mol Sci. 2019 Oct 17;20(20):5138. doi: 10.3390/ijms20205138. Int J Mol Sci. 2019. PMID: 31627272 Free PMC article.
-
Review of Immune-Related Adverse Events (irAEs) in Non-Small-Cell Lung Cancer (NSCLC)-Their Incidence, Management, Multiorgan irAEs, and Rechallenge.Biomedicines. 2022 Mar 28;10(4):790. doi: 10.3390/biomedicines10040790. Biomedicines. 2022. PMID: 35453540 Free PMC article. Review.
References
-
- Ferlay J, Soerjomataram I, Dikshit R, et al. : Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359-E386, 2015 - PubMed
-
- Gupta K, Miller JD, Li JZ, et al. : Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): A literature review. Cancer Treat Rev 34:193-205, 2008 - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical