Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Disease-Free Survival
Female
Humans
Ipilimumab
/ adverse effects
Male
Melanoma
Middle Aged
Molecular Targeted Therapy
Neoplasm Staging
Nivolumab
/ adverse effects
Proto-Oncogene Proteins B-raf
/ antagonists & inhibitors
Skin Neoplasms
Treatment Outcome
Young Adult
BRAF
immunotherapy
ipilimumab
melanoma
nivolumab
targeted therapy
Journal
Pigment cell & melanoma research
ISSN: 1755-148X
Titre abrégé: Pigment Cell Melanoma Res
Pays: England
ID NLM: 101318927
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
13
02
2019
revised:
03
09
2019
accepted:
12
09
2019
pubmed:
7
10
2019
medline:
30
12
2020
entrez:
7
10
2019
Statut:
ppublish
Résumé
The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine-protein kinase B-Raf (BRAF)-targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment-naïve and 22% failed first-line BRAF/MEK inhibitors. Treatment-related adverse events occurred in 67% of patients, grade 3-5 in 38%. The overall objective response rate was 41%, 57% in treatment-naïve and 21% in BRAF/MEK failure patients. Median progression-free survival was 4.0 months (95% CI, 3.0-6.0) in the whole cohort, 11.0 months (95% CI, 6.0-NR) in treatment-naïve and 2.0 months (95% CI, 1.4-4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real-world population. While first-line efficacy appears comparable to trial populations, BRAF-mutant patients failing prior BRAF/MEK inhibitors show less response.
Substances chimiques
Ipilimumab
0
Nivolumab
31YO63LBSN
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
358-365Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Ascierto, P. A., Del Vecchio, M., Robert, C., Mackiewicz, A., Chiarion-Sileni, V., Arance, A., … Maio, M. (2017). Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: A randomised, double-blind, multicentre, phase 3 trial. The Lancet Oncology, 18(5), 611-622. https://doi.org/10.1016/S1470-2045(17)30231-0
Ascierto, P. A., McArthur, G. A., Dréno, B., Atkinson, V., Liszkay, G., Di Giacomo, A. M., … Larkin, J. (2016). Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): Updated efficacy results from a randomised, double-blind, phase 3 trial. The Lancet Oncology, 17(9), 1248-1260. https://doi.org/10.1016/S1470-2045(16)30122-X
Bowyer, S., Prithviraj, P., Lorigan, P., Larkin, J., McArthur, G., Atkinson, V., … Klein, O. (2016). Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. British Journal of Cancer, 114(10), 1084-1089. https://doi.org/10.1038/bjc.2016.107
Eggermont, A. M. M., Blank, C. U., Mandala, M., Long, G. V., Atkinson, V., Dalle, S., … Robert, C. (2018). Adjuvant pembrolizumab versus placebo in resected stage III. Melanoma., 378(19), 1789-1801. https://doi.org/10.1056/NEJMoa1802357
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., … Verweij, J. (2009). New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal of Cancer, 45(2), 228-247. https://doi.org/10.1016/j.ejca.2008.10.026
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., … Urba, W. J. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine, 363(8), 711-723. https://doi.org/10.1056/NEJMoa1003466
Hugo, W., Shi, H., Sun, L. U., Piva, M., Song, C., Kong, X., … Lo, R. S. (2015). Non-genomic and immune evolution of melanoma acquiring MAPKi resistance. Cell, 162(6), 1271-1285. https://doi.org/10.1016/j.cell.2015.07.061
Kakavand, H., Wilmott, J. S., Menzies, A. M., Vilain, R., Haydu, L. E., Yearley, J. H., … Scolyer, R. A. (2015). PD-L1 expression and tumor-infiltrating lymphocytes define different subsets of MAPK inhibitor-treated melanoma patients. Clinical Cancer Research, 21(14), 3140-3148. https://doi.org/10.1158/1078-0432.CCR-14-2023
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., … Wolchok, J. D. (2015). Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. New England Journal of Medicine, 373(1), 23-34. https://doi.org/10.1056/NEJMoa1504030
Long, G. V., Atkinson, V., Lo, S., Sandhu, S., Guminski, A. D., Brown, M. P., … McArthur, G. A. (2018). Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: A multicentre randomised phase 2 study. The Lancet Oncology, 19(5), 672-681. https://doi.org/10.1016/S1470-2045(18)30139-6
Long, G. V., Flaherty, K. T., Stroyakovskiy, D., Gogas, H., Levchenko, E., de Braud, F., … Grob, J.-J. (2017). Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: Long-term survival and safety analysis of a phase 3 study. Annals of Oncology, 28(7), 1631-1639. https://doi.org/10.1093/annonc/mdx176
Long, G. V., Hauschild, A., Santinami, M., Atkinson, V., Mandala, M., Chiarion-Sileni, V., … Kirkwood, J. M. (2017). Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. New England Journal of Medicine, 377(19), 1813-1823. https://doi.org/10.1056/NEJMoa1708539
Olson, D., Luke, J. J., Hallmeyer, S., Bajaj, M., Carll, T., Krausz, T., … Khushalani, N. I. (2018). Phase II trial of pembrolizumab (pembro) plus 1 mg/kg ipilimumab (ipi) immediately following progression on anti-PD-1 Ab in melanoma (mel). Journal of Clinical Oncology, 36(15_suppl), 9514-9514. https://doi.org/10.1200/JCO.2018.36.15_suppl.9514
Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., … Hodi, F. S. (2015). Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. New England Journal of Medicine, 372(21), 2006-2017. https://doi.org/10.1056/NEJMoa1414428
Schachter, J., Ribas, A., Long, G. V., Arance, A., Grob, J.-J., Mortier, L., … Robert, C. (2017). Pembrolizumab versus ipilimumab for advanced melanoma: Final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet, 390(10105), 1853-1862. https://doi.org/10.1016/S0140-6736(17)31601-X
Schadendorf, D., Long, G. V., Stroiakovski, D., Karaszewska, B., Hauschild, A., Levchenko, E., … Robert, C. (2017). Three-year pooled analysis of factors associated with clinical outcomes across dabrafenib and trametinib combination therapy phase 3 randomised trials. European Journal of Cancer, 82, 45-55. https://doi.org/10.1016/j.ejca.2017.05.033
Tawbi, H. A., Forsyth, P. A., Algazi, A., Hamid, O., Hodi, F. S., Moschos, S. J., … Margolin, K. (2018). Combined nivolumab and ipilimumab in melanoma metastatic to the brain. New England Journal of Medicine, 379(8), 722-730. https://doi.org/10.1056/NEJMoa1805453
Tétu, P., Mangana, J., Dummer, R., Dutriaux, C., Beneton, N., Dalle, S., … Lebbe, C. (2018). Benefit of the nivolumab and ipilimumab combination in pretreated advanced melanoma. European Journal of Cancer, 93, 147-149. https://doi.org/10.1016/j.ejca.2018.01.062
Thompson, J. F., Scolyer, R. A., & Kefford, R. F. (2005). Cutaneous melanoma. Lancet, 365(9460), 687-701. https://doi.org/10.1016/S0140-6736(05)17951-3
Weber, J., Mandala, M., Del Vecchio, M., Gogas, H. J., Arance, A. M., Cowey, C. L., … Ascierto, P. A. (2017). Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. New England Journal of Medicine, 377(19), 1824-1835. https://doi.org/10.1056/NEJMoa1709030
Wolchok, J. D., Chiarion-Sileni, V., Gonzalez, R., Rutkowski, P., Grob, J.-J., Cowey, C. L., … Larkin, J. (2017). Overall survival with combined nivolumab and ipilimumab in advanced melanoma. New England Journal of Medicine, 377(14), 1345-1356. https://doi.org/10.1056/NEJMoa1709684
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., … Sznol, M. (2013). Nivolumab plus ipilimumab in advanced melanoma. New England Journal of Medicine, 369(2), 122-133. https://doi.org/10.1056/NEJMoa1302369
Zimmer, L., Apuri, S., Eroglu, Z., Kottschade, L. A., Forschner, A., Gutzmer, R., … Khushalani, N. I. (2017). Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. European Journal of Cancer, 75, 47-55. https://doi.org/10.1016/j.ejca.2017.01.009