Pembrolizumab in Patients with Advanced Metastatic Germ Cell Tumors.
Germ cell tumor
Non-progression rate
Pembrolizumab
Phase II
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
11
11
2020
accepted:
08
01
2021
pubmed:
26
1
2021
medline:
13
7
2021
entrez:
25
1
2021
Statut:
ppublish
Résumé
Advanced germ cell tumors are aggressive and associated with poor prognosis. Pembrolizumab was overall well tolerated in 12 heavily pretreated patients. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. Published data of immunotherapeutic agents in patients with advanced germ cell tumors are confirmed. The limited antitumor activity of immunotherapy in germ cell tumors is, at least partially, attributed to tumor biology (low tumor mutational burden; low PD-1 expression) and other poor-risk features. Tumor profiling to understand the mechanisms of resistance to pembrolizumab and innovative clinical trials that may include immunotherapy are warranted. Advanced germ cell tumors are associated with poor prognosis. We investigated the role of pembrolizumab in patients with advanced germ cell tumors. We analyzed a prespecified cohort of an open-label, phase II clinical trial in which patients with advanced germ cell tumors were treated with pembrolizumab (200 mg) intravenously every 21 days. The endpoints of the study were the non-progression rate (NPR) at 27 weeks, safety, and tolerability. An NPR >20% was considered successful and worthy of further pursuit. From August 2016 to February 2018, 12 patients (10 men, 2 women) were treated (median age, 35 years [range, 22-63 years]; median number of prior systemic therapies, 3.5 [range, 2-7]; median number of metastatic sites, 3 [range, 2-8]). Overall, pembrolizumab was well tolerated. One patient experienced both grade 1 immune-related skin rash and grade 3 immune-related pneumonitis. No patient died from toxicity. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. No objective response was noted. The median progression-free survival was 2.4 months (95% confidence interval [CI], 1.5-4.5 months), and the median overall survival was 10.6 months (95% CI, 4.6-27.1 months). The 27-week NPR was 9.0% (95% CI, 0.23-41.2%). Overall, pembrolizumab was safe and had limited antitumor activity in these patients. In the advanced, metastatic setting, tumor profiling to understand the mechanisms of resistance to immunotherapy and innovative clinical trials to identify efficacious combination regimens rather than off-label use of pembrolizumab are warranted.
Sections du résumé
LESSONS LEARNED
Advanced germ cell tumors are aggressive and associated with poor prognosis. Pembrolizumab was overall well tolerated in 12 heavily pretreated patients. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. Published data of immunotherapeutic agents in patients with advanced germ cell tumors are confirmed. The limited antitumor activity of immunotherapy in germ cell tumors is, at least partially, attributed to tumor biology (low tumor mutational burden; low PD-1 expression) and other poor-risk features. Tumor profiling to understand the mechanisms of resistance to pembrolizumab and innovative clinical trials that may include immunotherapy are warranted.
BACKGROUND
Advanced germ cell tumors are associated with poor prognosis. We investigated the role of pembrolizumab in patients with advanced germ cell tumors.
METHODS
We analyzed a prespecified cohort of an open-label, phase II clinical trial in which patients with advanced germ cell tumors were treated with pembrolizumab (200 mg) intravenously every 21 days. The endpoints of the study were the non-progression rate (NPR) at 27 weeks, safety, and tolerability. An NPR >20% was considered successful and worthy of further pursuit.
RESULTS
From August 2016 to February 2018, 12 patients (10 men, 2 women) were treated (median age, 35 years [range, 22-63 years]; median number of prior systemic therapies, 3.5 [range, 2-7]; median number of metastatic sites, 3 [range, 2-8]). Overall, pembrolizumab was well tolerated. One patient experienced both grade 1 immune-related skin rash and grade 3 immune-related pneumonitis. No patient died from toxicity. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. No objective response was noted. The median progression-free survival was 2.4 months (95% confidence interval [CI], 1.5-4.5 months), and the median overall survival was 10.6 months (95% CI, 4.6-27.1 months). The 27-week NPR was 9.0% (95% CI, 0.23-41.2%).
CONCLUSION
Overall, pembrolizumab was safe and had limited antitumor activity in these patients. In the advanced, metastatic setting, tumor profiling to understand the mechanisms of resistance to immunotherapy and innovative clinical trials to identify efficacious combination regimens rather than off-label use of pembrolizumab are warranted.
Identifiants
pubmed: 33491277
doi: 10.1002/onco.13682
pmc: PMC8265349
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
pembrolizumab
DPT0O3T46P
Banques de données
ClinicalTrials.gov
['NCT02721732']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
558-e1098Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003167
Pays : United States
Informations de copyright
© AlphaMed Press; the data published online to support this summary are the property of the authors.
Références
Eur J Radiol. 2015 Jul;84(7):1259-68
pubmed: 25937524
Int J Urol. 2018 Apr;25(4):337-344
pubmed: 29345008
Oncoimmunology. 2018 Jun 20;7(12):e1396403
pubmed: 30524878
Transplantation. 2009 Jun 27;87(12):1778-86
pubmed: 19543053
Eur J Cancer. 2017 May;76:1-7
pubmed: 28262583
Crit Rev Oncol Hematol. 2019 Nov;143:130-138
pubmed: 31634730
J Immunother Cancer. 2020 Mar;8(1):
pubmed: 32188704
Lancet Oncol. 2017 Mar;18(3):e143-e152
pubmed: 28271869
Cancer Immunol Res. 2016 Nov;4(11):903-909
pubmed: 27638840
Mol Cancer Ther. 2017 Nov;16(11):2598-2608
pubmed: 28835386
J Immunother Cancer. 2018 Oct 19;6(1):108
pubmed: 30340549
Lancet. 2016 Apr 9;387(10027):1540-1550
pubmed: 26712084
Ann Oncol. 2020 Sep;31(9):1115-1118
pubmed: 32771306
Ann Oncol. 2016 Feb;27(2):300-5
pubmed: 26598537
Clin Genitourin Cancer. 2017 Oct;15(5):e855-e857
pubmed: 28465048
Ann Oncol. 2018 Jan 1;29(1):209-214
pubmed: 29045540
Oncologist. 2019 Apr;24(4):e142-e145
pubmed: 30659078
Invest New Drugs. 2019 Aug;37(4):748-754
pubmed: 31152292
Br J Cancer. 2015 Jul 28;113(3):411-3
pubmed: 26171934