Pembrolizumab as first-line treatment for metastatic uveal melanoma.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
Female
Humans
Male
Melanoma
/ drug therapy
Middle Aged
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Progression-Free Survival
Prospective Studies
Uveal Neoplasms
/ drug therapy
First line
Immunotherapy
Liver metastases
Pembrolizumab
Uveal melanoma
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
25
07
2018
accepted:
30
05
2019
pubmed:
9
6
2019
medline:
6
7
2019
entrez:
9
6
2019
Statut:
ppublish
Résumé
No standard treatment has been defined for metastatic uveal melanoma (mUM). Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease. In this prospective observational cohort single arm study, we investigated efficacy and safety of Pembrolizumab as first-line therapy for mUM. The efficacy was evaluated in terms of progression-free survival (PFS), response rate and overall survival (OS). Toxicity was also assessed. Seventeen patients were enrolled. A median of 8 cycles were administered (range 2-28). Two patients achieved partial response (11.7%), 6 a disease stabilization (35.3%), whereas 9 (53%) had a progression. No complete response was observed. PFS of the overall population was 3.8 months. PFS was 9.7 months for patients with an interval higher than 5 years from diagnosis of primary tumor to metastatic disease and 2.6 months for patients with an interval lower than 5 years [p = 0.039, HR 0.2865 (95% CI 0.0869-0.9443)]. Median OS was not reached. The two responding patients were still on treatment with Pembrolizumab at the time of data analysis. Survival was 12.8 months for patients with clinical benefit, while OS for progressive patients was 3.1 months. PD-L1 expression and genomic abnormalities predictive of relapse after diagnosis of primary tumor were not associated with PFS. Toxicity was mild, without grade 3-4 side effects. The efficacy of Pembrolizumab does not seem particularly different when compared to other agents for mUM, but responding patients had a remarkable disease control.
Sections du résumé
BACKGROUND
BACKGROUND
No standard treatment has been defined for metastatic uveal melanoma (mUM). Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease.
PATIENTS AND METHODS
METHODS
In this prospective observational cohort single arm study, we investigated efficacy and safety of Pembrolizumab as first-line therapy for mUM. The efficacy was evaluated in terms of progression-free survival (PFS), response rate and overall survival (OS). Toxicity was also assessed.
RESULTS
RESULTS
Seventeen patients were enrolled. A median of 8 cycles were administered (range 2-28). Two patients achieved partial response (11.7%), 6 a disease stabilization (35.3%), whereas 9 (53%) had a progression. No complete response was observed. PFS of the overall population was 3.8 months. PFS was 9.7 months for patients with an interval higher than 5 years from diagnosis of primary tumor to metastatic disease and 2.6 months for patients with an interval lower than 5 years [p = 0.039, HR 0.2865 (95% CI 0.0869-0.9443)]. Median OS was not reached. The two responding patients were still on treatment with Pembrolizumab at the time of data analysis. Survival was 12.8 months for patients with clinical benefit, while OS for progressive patients was 3.1 months. PD-L1 expression and genomic abnormalities predictive of relapse after diagnosis of primary tumor were not associated with PFS. Toxicity was mild, without grade 3-4 side effects.
CONCLUSIONS
CONCLUSIONS
The efficacy of Pembrolizumab does not seem particularly different when compared to other agents for mUM, but responding patients had a remarkable disease control.
Identifiants
pubmed: 31175402
doi: 10.1007/s00262-019-02352-6
pii: 10.1007/s00262-019-02352-6
pmc: PMC6584707
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1179-1185Références
Invest Ophthalmol Vis Sci. 2003 Nov;44(11):4651-9
pubmed: 14578381
Cancer. 2005 Mar 1;103(5):1000-7
pubmed: 15651058
J Clin Oncol. 2005 Nov 1;23(31):8076-80
pubmed: 16258106
Arch Ophthalmol. 2005 Dec;123(12):1639-43
pubmed: 16344433
Mol Cell. 2007 Jul 6;27(1):107-19
pubmed: 17612494
Invest Ophthalmol Vis Sci. 2009 Jan;50(1):273-80
pubmed: 18791172
J Clin Invest. 2010 Jun;120(6):2030-9
pubmed: 20501944
Cancer Immunol Immunother. 2012 Jan;61(1):41-8
pubmed: 21833591
Melanoma Res. 2013 Feb;23(1):79-81
pubmed: 23211837
Am J Pathol. 2013 Mar;182(3):678-87
pubmed: 23357503
Cancer. 2014 Mar 15;120(6):781-9
pubmed: 24301420
PLoS One. 2015 Mar 11;10(3):e0118564
pubmed: 25761109
N Engl J Med. 2015 Jun 25;372(26):2521-32
pubmed: 25891173
Nat Genet. 2016 Jun;48(6):675-80
pubmed: 27089179
Oncoimmunology. 2016 Feb 18;5(5):e1143997
pubmed: 27467964
Cancer. 2016 Nov 15;122(21):3344-3353
pubmed: 27533448
Cancer Metastasis Rev. 2017 Mar;36(1):109-140
pubmed: 28229253
Curr Oncol Rep. 2017 Jul;19(7):45
pubmed: 28508938
Eur J Cancer. 2017 Sep;82:56-65
pubmed: 28648699
Cancer Cell. 2017 Aug 14;32(2):204-220.e15
pubmed: 28810145
Melanoma Res. 2017 Dec;27(6):591-595
pubmed: 29076951
Immunotherapy. 2017 Dec;9(16):1323-1330
pubmed: 29185395
J Clin Oncol. 2018 Apr 20;36(12):1232-1239
pubmed: 29528792
Mod Pathol. 2018 Aug;31(8):1201-1210
pubmed: 29581543
Pigment Cell Melanoma Res. 2018 Nov;31(6):661-672
pubmed: 29738114
Nat Commun. 2018 May 14;9(1):1866
pubmed: 29760383
Cancer. 1995 Nov 1;76(9):1665-70
pubmed: 8635073
Am J Clin Oncol. 1998 Dec;21(6):568-72
pubmed: 9856657