Efficacy and safety of nivolumab plus ipilimumab versus nivolumab alone in patients with advanced melanoma: a systematic review and meta-analysis

References

• Long GV, Swetter SM, Menzies AM, et al. Cutaneous melanoma. Lancet (London, England). 2023 Aug 5;402(10400):485–502. doi: 10.1016/S0140-6736(23)00821-8
   PubMed Web of Science ®Google Scholar
• Schadendorf D, van Akkooi ACJ, Berking C, et al. Melanoma. Lancet (London, England). 2018 Sep 15;392(10151):971–984. doi: 10.1016/S0140-6736(18)31559-9
   PubMed Web of Science ®Google Scholar
• Tryggvadóttir L, Gislum M, Hakulinen T, et al. Trends in the survival of patients diagnosed with malignant melanoma of the skin in the Nordic countries 1964-2003 followed up to the end of 2006. Acta Oncol. 2010 Jun;49(5):665–672.
   PubMed Web of Science ®Google Scholar
• Aggarwal P, Knabel P, Fleischer AB Jr. United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019. J Am Acad Dermatol. 2021 Aug;85(2):388–395. doi: 10.1016/j.jaad.2021.03.109
   PubMed Web of Science ®Google Scholar
• Bolick NL, Geller AC. Epidemiology of melanoma. Hematol Oncol Clin North Am. 2021 Feb;35(1):57–72. doi: 10.1016/j.hoc.2020.08.011
   PubMed Web of Science ®Google Scholar
• Gupta M, Stukalin I, Meyers D, et al. Treatment-free survival after nivolumab vs pembrolizumab vs nivolumab-ipilimumab for advanced melanoma. JAMA Netw Open. 2023 Jun 1;6(6):e2319607. doi: 10.1001/jamanetworkopen.2023.19607
   PubMed Web of Science ®Google Scholar
• Abboud K, Umoru G, Esmail A, et al. Immune checkpoint inhibitors for solid tumors in the adjuvant setting: current progress, future directions, and role in transplant oncology. Cancers (Basel). 2023 Feb 23;15(5):1433. doi: 10.3390/cancers15051433
   PubMed Web of Science ®Google Scholar
• Carlino MS, Larkin J, Long GV. Immune checkpoint inhibitors in melanoma. Lancet (London, England). 2021 Sep 11;398(10304):1002–1014. doi: 10.1016/S0140-6736(21)01206-X
   PubMed Web of Science ®Google Scholar
• Weber JS, Schadendorf D, Del Vecchio M, et al. Adjuvant therapy of nivolumab combined with ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or stage IV melanoma (CheckMate 915). J Clin Oncol. 2023 Jan 20;41(3):517–527. doi: 10.1200/JCO.22.00533
   PubMed Web of Science ®Google Scholar
• Willsmore ZN, Coumbe BGT, Crescioli S, et al. Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: treatment of melanoma and immune mechanisms of action. Eur J Immunol. 2021 Mar;51(3):544–556.
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-Term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. JCO. 2022 Jan 10;40(2):127–137. doi: 10.1200/JCO.21.02229
   Google Scholar
• Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu Rev Pathol Mech Dis. 2021 Jan 24;16(1):223–249. doi: 10.1146/annurev-pathol-042020-042741
   PubMedGoogle Scholar
• Namikawa K, Yamazaki N. Targeted therapy and immunotherapy for melanoma in Japan. Curr Treat Options Oncol. 2019 Jan 24;20(1):7. doi: 10.1007/s11864-019-0607-8
   PubMed Web of Science ®Google Scholar
• Kim DW, Trinh VA, Hwu WJ. Ipilimumab in the treatment of advanced melanoma - a clinical update. Expert Opin Biol Ther. 2014 Nov;14(11):1709–1718. doi: 10.1517/14712598.2014.963053
   PubMed Web of Science ®Google Scholar
• Guo W, Wang H, Li C. Signal pathways of melanoma and targeted therapy. signal transduction and targeted therapy. Signal Transduct Target Ther. 2021 Dec 20;6(1):424. doi: 10.1038/s41392-021-00827-6
   PubMed Web of Science ®Google Scholar
• Schwarze JK, Garaud S, Jansen YJL, et al. Low-dose nivolumab with or without Ipilimumab as adjuvant therapy following the resection of melanoma metastases: a sequential dual cohort phase II clinical trial. Cancers (Basel). 2022 Jan 28;14(3):682. doi: 10.3390/cancers14030682
   PubMed Web of Science ®Google Scholar
• Jenkins RW, Fisher DE. Treatment of advanced melanoma in 2020 and beyond. J Invest Dermatol. 2021 Jan;141(1):23–31. doi: 10.1016/j.jid.2020.03.943
   PubMed Web of Science ®Google Scholar
• Lebbé C, Meyer N, Mortier L, et al. Evaluation of two dosing regimens for nivolumab in combination with ipilimumab in patients with advanced melanoma: results from the phase IIIb/IV CheckMate 511 trial. JCO. 2019 Apr 10;37(11):867–875. doi: 10.1200/JCO.18.01998
   Google Scholar
• Ascierto PA, Del Vecchio M, Mandalá M, et al. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1465–1477.
   PubMed Web of Science ®Google Scholar
• Hodi FS, Chesney J, Pavlick AC, et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1558–1568.
   PubMed Web of Science ®Google Scholar
• Leonardi GC, Falzone L, Salemi R, et al. Cutaneous melanoma: from pathogenesis to therapy (review). Int J Oncol. 2018 Apr;52(4):1071–1080.
   PubMed Web of Science ®Google Scholar
• Livingstone E, Zimmer L, Hassel JC, et al. Adjuvant nivolumab plus ipilimumab or nivolumab alone versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): final results of a randomised, double-blind, phase 2 trial. Lancet (London, England). 2022 Oct 1;400(10358):1117–1129. doi: 10.1016/S0140-6736(22)01654-3
   PubMed Web of Science ®Google Scholar
• Knispel S, Gassenmaier M, Menzies AM, et al. Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition. Eur J Cancer. 2021 May;148:61–75. doi: 10.1016/j.ejca.2021.01.034
   PubMed Web of Science ®Google Scholar
• Albin N, Monard A, Lapiere J. The clinical added value of the addition of anti-CTL-4 to anti-PD-1 alone is questionable and clearly increasing toxicity regarding pivotal studies in the treatment of melanoma and renal carcinoma. Cancer Chemother Pharmacol. 2019 May;83(5):1003–1005. doi: 10.1007/s00280-019-03804-7
   PubMed Web of Science ®Google Scholar
• Long GV, Atkinson V, Lo S, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 May;19(5):672–681.
   PubMed Web of Science ®Google Scholar
• Amaria RN, Reddy SM, Tawbi HA, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nature Med. 2018 Nov;24(11):1649–1654.
   PubMed Web of Science ®Google Scholar
• Lazaroff J, Bolotin D. Targeted therapy and immunotherapy in melanoma. Dermatol Clin. 2023 Jan;41(1):65–77. doi: 10.1016/j.det.2022.07.007
   PubMed Web of Science ®Google Scholar
• Hartman RI, Lin JY. Cutaneous melanoma-a review in detection, staging, and management. Hematol Oncol Clin North Am. 2019 Feb;33(1):25–38. doi: 10.1016/j.hoc.2018.09.005
   PubMed Web of Science ®Google Scholar
• Chennamadhavuni A, Abushahin L, Jin N, et al. Risk factors and biomarkers for immune-related adverse events: a practicaL guide to identifying high-risk patients and rechallenging immune checkpoint inhibitors. Front Immunol. 2022;13:779691. doi: 10.3389/fimmu.2022.779691
   PubMed Web of Science ®Google Scholar
• Kempf W, Mitteldorf C. Cutaneous T-cell lymphomas-An update 2021. Hematol Oncol. 2021 Jun;39(Suppl 1):46–51. doi: 10.1002/hon.2850
   PubMedGoogle Scholar
• Campbell KM, Amouzgar M, Pfeiffer SM, et al. Prior anti-CTLA-4 therapy impacts molecular characteristics associated with anti-PD-1 response in advanced melanoma. Cancer Cell. 2023 Apr 10;41(4):791–806.e4. doi: 10.1016/j.ccell.2023.03.010
   PubMed Web of Science ®Google Scholar
• Kleffel S, Posch C, Barthel SR, et al. Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth. Cell. 2015 Sep 10;162(6):1242–1256. doi: 10.1016/j.cell.2015.08.052
   PubMed Web of Science ®Google Scholar
• Liu D, Schilling B, Liu D, et al. Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma. Nature Med. 2019 Dec;25(12):1916–1927.
   PubMed Web of Science ®Google Scholar
• Geisler AN, Phillips GS, Barrios DM, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020 Nov;83(5):1255–1268.
   PubMed Web of Science ®Google Scholar
• Zimmer L, Livingstone E, Hassel JC, et al. Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet (London, England). 2020 May 16;395(10236):1558–1568. doi: 10.1016/S0140-6736(20)30417-7
   PubMed Web of Science ®Google Scholar
• Marchetti P, Botticelli A, Ascierto AP, et al. Agnostic evaluation of ipilimumab and nivolumab association: a metanalysis. J Transl Med. 2020 Nov 25;18(1):446. doi: 10.1186/s12967-020-02588-2
   PubMed Web of Science ®Google Scholar
• Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019 Oct 17;381(16):1535–1546. doi: 10.1056/NEJMoa1910836
   PubMed Web of Science ®Google Scholar
• Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Nov;19(11):1480–1492.
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013 Jul 11;369(2):122–133. doi: 10.1056/NEJMoa1302369
   PubMed Web of Science ®Google Scholar
• Garbe C, Amaral T, Peris K, et al. European consensus-based interdisciplinary guideline for melanoma. Part 2: treatment - update 2022. Eur J Cancer. 2022 Jul;170:256–284. doi: 10.1016/j.ejca.2022.04.018
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017 Oct 5;377(14):1345–1356. doi: 10.1056/NEJMoa1709684
   PubMed Web of Science ®Google Scholar
• Friedman CF, Spencer C, Cabanski CR, et al. Ipilimumab alone or in combination with nivolumab in patients with advanced melanoma who have progressed or relapsed on PD-1 blockade: clinical outcomes and translational biomarker analyses. J Immunother Cancer. 2022 Jan;10(1):e003853.
   PubMed Web of Science ®Google Scholar
• Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016 Aug;13(8):473–486.
   PubMed Web of Science ®Google Scholar
• Patrinely JR Jr., Johnson R, Lawless AR, et al. Chronic immune-related adverse events following adjuvant anti-PD-1 therapy for high-risk resected melanoma. JAMA Oncol. 2021 May 1;7(5):744–748. doi: 10.1001/jamaoncol.2021.0051
   PubMed Web of Science ®Google Scholar
• Mao YT, Wang Y, Chen XX, et al. Comparative severe dermatologic toxicities of immune checkpoint inhibitors in malignant melanoma: a systematic review and network meta-analysis. J Cosmet Dermatol. 2023 Nov 27. doi: 10.1111/jocd.16105
   Web of Science ®Google Scholar
• Swetter SM. NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021. J Natl Compr Canc Netw. 2021;19(4):364–376. doi: 10.6004/jnccn.2021.0018
   PubMed Web of Science ®Google Scholar
• Seth R, Agarwala SS, Messersmith H, et al. Systemic therapy for melanoma: ASCO guideline update. JCO. 2023 Oct 20;41(30):4794–4820. doi: 10.1200/JCO.23.01136
   Google Scholar