Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1–2 trial

Geoerger, Birgit; Kang, Hyoung Jin; Yalon-Oren, Michal; Marshall, Lynley V.; Vézina, Catherine; Pappo, Alberto S.; Laetsch, Theodore W.; Petrilli, Antônio Sérgio; Ebinger, Martin; Toporski, Jacek; Bender, Julia Glade; Nicholls, Wayne; Fox, Elizabeth; DuBois, Steven G.; Macy, Margaret E.; Cohn, Susan L.; Pathiraja, Kumudu; Diede, Scott J.; Ebbinghaus, Scot; Pinto, Navin

doi:10.1016/s1470-2045(19)30671-0

Cited by 205 publications

(183 citation statements)

References 31 publications

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“…In advanced ACC, pembrolizumab showed a significant and durable antitumor activity with a manageable safety profile ( 43 – 45 ). In the recent interim analysis of the phases 1–2 study, KEYNOTE-051 conducted in the pediatric setting, two of four patients with ACC showed partial responses to pembrolizumab therapy ( 46 ). In our cohort, two patients were treated by immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Clinical, Genetic, and Prognostic Features of Adrenocortical Tumors in Children: A 10-Year Single-Center Experience

et al. 2020

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Background and Aims: Pediatric adrenocortical tumors (ACTs) are very rare endocrine neoplasms in childhood. In this study, we performed a retrospective analysis of children with ACT treated at our institution by examining clinical and genetic disease features, treatment strategies, and outcomes. Methods: We retrospectively analyzed a cohort of 13 children treated at the Bambino Gesù Children's Hospital from November 2010 to March 2020. Results: The median age at diagnosis was 17 months (range = 0-82 months). The female: male ratio was 3.3/1. Mixed symptomatology (>1 hormone abnormality) was the most common presentation (46.1%). In three cases, the tumor was detected during prenatal or perinatal echographic screening. All patients presented with localized disease at diagnosis and underwent total adrenalectomy. Six patients were identified as having malignancies according to the Wieneke scoring system, five benign, and two undetermined. Seven patients underwent mitotane adjuvant therapy for 12 months. There was metastatic disease in three patients, with no correlation with age or Wieneke score. The most common sites of metastases were the liver and lungs. Metastatic patients were treated with surgery (n = 2), mitotane (n = 1), chemotherapy (n = 2) associated with anti-EGFR (n = 1), or immunotherapy with anti-PD1 (pembrolizumab) (n = 1); two patients achieved complete disease remission. Overall 2-and 5-year survival rates were 100%, with a median follow-up of 5 years (range = 2-9.5 years). Two-and 5-year disease free survival was 76.9 and 84.6%, respectively (95% confidence interval = −66.78-114.76 months). All patients are alive, 12 without disease, and one with stable disease. Genetic analyses showed TP53 germline mutations in six of eight patients analyzed (five inherited, one de novo). One patient had Beckwith-Wiedemann syndrome, with mosaic paternal uniparental disomy of chromosome 11, in both neoplastic and healthy adrenal tissue. Miele et al. Adrenocortical Tumors in Children Conclusion: We report the cases of 13 patients treated for ACT, including 12 aged <4 years at diagnosis, with a relative short time from symptoms onset. Our cohort experienced an excellent prognosis. TP53 mutation was found in 75% of tested patients (6/8) confirming the need to perform genetic tests and familial counseling in this disease.

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Section: Discussionmentioning

confidence: 99%

Clinical, Genetic, and Prognostic Features of Adrenocortical Tumors in Children: A 10-Year Single-Center Experience

et al. 2020

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“…Over the past years, the applications of PD-1/PD-L1 checkpoint blockades in cancer have revolutionized oncology (28,29). Particularly, these approaches have guided immunotherapy strategies against multiple cancers, such as melanoma (30), lung cancer (31), glioblastoma (32) and liver cancer (33). However, the efficacy and responsiveness of immunotherapeutic agents significantly varies across GC patients, largely due to high tumor heterogeneity and molecular complexity (34).…”

Section: Discussionmentioning

confidence: 99%

Identification of TYROBP and C1QB as Two Novel Key Genes With Prognostic Value in Gastric Cancer by Network Analysis

Jiang

Ding

et al. 2020

Front. Oncol.

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Background: Gastric cancer (GC) is the fifth most frequently diagnosed malignancy, and the third leading cause of tumor-related mortalities worldwide. Due to a high heterogeneity in GC, its treatment and prognosis are challenging, necessitating urgent identification of novel prognostic predictors for GC patients. Methods: We downloaded RNA sequence data, from the Cancer Genome Atlas and microarray data from Gene Expression Omnibus database, then identified common differentially-expressed genes (DEGs) between GC and normal gastric tissues across four datasets. We then used a combination of protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) to identify key genes with prognostic value in GC. Thereafter, we used quantitative real time polymerase chain reaction (qRT-PCR) to validate expression of the identified key genes in the Zhejiang University (ZJU) cohort. Finally, we evaluated the relationships between gene expression and immune factors, including immune cells and biomarkers of immunotherapy. Results: Among 426 common DEGs screened, 333 and 93 were upregulated and downregulated, respectively. PPI network and WGCNA successfully identified the top 30 hub genes, among which PTPRC, TYROBP, CCR1, CYBB, LCP2, and C1QB were common. Furthermore, TYROBP and C1QB were negatively associated with prognosis of GC patients, implying that they were key GC predictors. Interestingly, TYROBP and C1QB were positively correlated with predictive biomarkers for GC immunotherapy, including PD-L1 expression, CD8 + T cells infiltration, and EBV status. Conclusions: TYROBP and C1QB were identified as two novel key genes with prognostic value in GC by network analysis.

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“…Two hundred and fifty-one patients have been recruited into three early phase trials of single agent immune checkpoint inhibitors which have been completed, including the PD-1 inhibitors pembrolizumab (155 enrolled, 154 treated) [12] and nivolumab (20 enrolled and treated) [13] and the PD-L1 inhibitor atezolizumab (90 enrolled, 87 treated) [14].…”

Section: Completed Early Phase Trials Of Single Agent Checkpoint Inhimentioning

confidence: 99%

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients

Pearson¹,

Rössig

Lesa

et al. 2020

European Journal of Cancer

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Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1–2 trial

Cited by 205 publications

References 31 publications

Clinical, Genetic, and Prognostic Features of Adrenocortical Tumors in Children: A 10-Year Single-Center Experience

Clinical, Genetic, and Prognostic Features of Adrenocortical Tumors in Children: A 10-Year Single-Center Experience

Identification of TYROBP and C1QB as Two Novel Key Genes With Prognostic Value in Gastric Cancer by Network Analysis

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients

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