Programmed cell death-Ligand 1 (PD-L1) expression and outcome in patients with squamous cell cancer of anal canal (SCCAC).

Gujja, Swetha; Williamson, Stephen K.; Batra, Anu; Saeed, Anwaar; Lai, Keith; Fogel, B.; James, Justin; Siegel, Eric; Govindarajan, Rangaswamy

doi:10.1200/jco.2015.33.15_suppl.3523

Cited by 4 publications

(3 citation statements)

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“…No evaluations of the use of anti-PD-1 therapy in the management of anal squamous cell carcinoma are currently reported in the literature. However, while not therapeutically evaluated, a retrospective study of PD-L1 positivity was associated with a non-statistically significant trend towards a poorer RFS in ASCC, consistent with what has been observed with other cancer types [ 24 ]. Finally, there were additionally a small subset of tumors found to have HER2 amplification by ISH, and when identified, these tumors could potentially be candidates for therapy with HER2-targeting agents.…”

Section: Discussionsupporting

confidence: 73%

Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas

et al. 2015

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Anal squamous cell carcinoma (ASCC) is a rare, HPV-associated malignancy typically diagnosed in early stages and definitively treated with chemoradiation. In situations where patients exhibit metastatic or recurrent disease, treatment options are severely limited. In this study, molecular alterations were identified that could be used to aid in therapeutic decisions for patients with metastatic or recurrent anal squamous cell carcinoma. Specimens from patients with this cancer were tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing, protein expression by immunohistochemistry, and gene amplification with in situ hybridization. Utilizing these techniques, novel treatment strategies that could be explored were identified, including potential benefit with anti-EGFR therapies, immune checkpoint inhibitors, topoisomerase inhibitors, and taxanes. The frequency of overexpression of proteins that mark resistance to chemotherapeutic drugs, such as MRP1 (chemotherapy efflux pump), ERCC1 (resistance to platinum-based chemotherapy), and thymidylate synthase (resistance to fluoropyrimidines) were also identified, suggesting a lack of benefit. This multiplatform strategy could be explored for its potential to generate a personalized treatment selection for patients with advanced ASCC, provide a guide for future therapeutic development for this cancer, and be extended to other rare cancer types as well.

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Section: Discussionsupporting

confidence: 73%

Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas

et al. 2015

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“…The tumors also had high immunohistochemistry (IHC) expression of EGFR (89%), TOP2A (85%), TOPO1 (67%) and low ERCC1 (49%), potentially conferring sensitivity to anti-EGFR antibodies, anthracyclines, irinotecan and platinum-based chemotherapies, respectively (16). Few tumors in this study were tested for PD-1 or PD-L1, and PD-L1 expression is known to correlate with a worse prognosis in SCCA (17). Another study preformed comprehensive genomic profiling on 574 SCCA tumors to analyze the prevalence as well as mutational profiling details of tumor suppressor gene CYLD (18).…”

Section: Introductionmentioning

confidence: 96%

Molecular characterization of squamous cell carcinoma of the anal canal

Armstrong

Malley

Wang

et al. 2021

J Gastrointest Oncol

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Background: Squamous cell carcinoma of the anal canal (SCCA) is an uncommon malignancy with limited therapeutic options. Nivolumab and pembrolizumab show promising results in patients with SCCA. Human papillomavirus (HPV)-negative tumors are frequently TP53-mutated (TP53-MT) and often resistant to therapy. Methods:We present a large molecularly-profiled cohort of SCCA, exploring the underlying biology of SCCA, differences between TP53-wild type (TP53-WT) and TP53-MT tumors, and differences between local and metastatic tumors. SCCA specimens (n=311) underwent multiplatform testing with immunohistochemistry (IHC), in situ hybridization (ISH) and next-generation sequencing (NGS). Tumor mutational burden (TMB) was calculated using only somatic nonsynonymous missense mutations. Chisquare testing was used for comparative analyses.Results: The most frequently mutated genes included PIK3CA (28.1%), KMT2D (19.5%), FBXW7 (12%), TP53 (12%) and PTEN (10.8%). The expression of PD-1 was seen in 68.8% and PD-L1 in 40.5% of tumors. High TMB was present in 6.7% of specimens. HER2 IHC was positive in 0.9%, amplification by chromogenic in situ hybridization (CISH) was seen 1.3%, and mutations in ERBB2 were present in 1.8% of tumors. The latter mutation has not been previously described in SCCA. When compared with TP53-WT tumors, TP53-MT tumors had higher rates of CDKN2A, EWSR1, JAK1, FGFR1 and BRAF mutations.PD-1 and PD-L1 expression were similar, and high TMB did not correlate with PD-1 (P=0.50) or PD-L1 (P=0.52) expression.Conclusions: Molecular profiling differences between TP53-MT and TP53-WT SCCA indicate different carcinogenic pathways which may influence response to therapy. Low frequency mutations in several druggable genes may provide therapeutic opportunities for patients with SCCA.

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“…A retrospective study (Gujja et al, 2015) of 41 patients with SCAC reported a prevalence of programmed death-ligand 1 (PD-L1) expression of 56%. No significant differences in survival were noted between patients with varying levels of PD-L1 expression.…”

Section: Role Of Immunotherapy In the Treatment Of Metastatic Scacmentioning

confidence: 99%

Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy

Casadei-Gardini

Passardi

Fornaro

et al. 2018

Critical Reviews in Oncology/Hematology

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The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However, interesting data have recently emerged on the use of anti-epidermal growth factor receptor (EGFR) agents and immunotherapy in advanced disease. Thus, new avenues of research are opening up that will hopefully lead to more effective therapeutic strategies. We provide an overview of the latest studies published on this tumor and discuss the possible future therapeutic options for combination therapy, anti-EGFR treatment and radiotherapy.

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Programmed cell death-Ligand 1 (PD-L1) expression and outcome in patients with squamous cell cancer of anal canal (SCCAC).

Cited by 4 publications

References 0 publications

Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas

Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas

Molecular characterization of squamous cell carcinoma of the anal canal

Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy

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