Antoine Desilets, Justin Lucas, Lisa F Licitra, Sunny Lu, Archie Tse, Tom Tang, Kevin Dreyer, Nanhai He, Lars E Birgerson, Sandrine Faivre, Denis Soulières
{"title":"布帕利西布和紫杉醇治疗头颈部鳞状细胞癌：BERIL-1研究中疗效的免疫基因组生物标志物","authors":"Antoine Desilets, Justin Lucas, Lisa F Licitra, Sunny Lu, Archie Tse, Tom Tang, Kevin Dreyer, Nanhai He, Lars E Birgerson, Sandrine Faivre, Denis Soulières","doi":"10.1007/s11523-024-01126-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>BERIL-1 was a randomized phase 2 study that studied paclitaxel with either buparlisib, a pan-class I PIK3 inhibitor, or placebo in patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Considering the therapeutic paradigm shift with immune checkpoint inhibitors (ICIs) now approved in the first-line setting, we present an updated immunogenomic analysis of patients enrolled in BERIL-1, including patients with immune-infiltrated tumors.</p><p><strong>Objective: </strong>The objective of this study was to identify biomarkers predictive of treatment efficacy in the context of the post-ICI therapeutic landscape.</p><p><strong>Patients and methods: </strong>Genomic analyses were performed at baseline on tumor and/or plasma circulating DNA (ctDNA) samples, and immunohistochemistry (IHC) studies, including immune infiltration [tumor-infiltrating lymphocytes (TILs) and CD8 expression], were performed on tumor samples. Immunogenomic biomarkers were correlated to overall survival (OS).</p><p><strong>Results: </strong>Among 158 patients enrolled in BERIL-1, either tumor (53.2%; n = 84) or ctDNA samples (70.8%; n = 112) were available in 85.4% (n = 135). The most commonly mutated genes were TP53 (57.0%), NOTCH1 (23.7%), and PIK3CA (22.2%). In the IHC studies, 98.6% (n = 68/69) of patients were TILs positive in the buparlisib arm versus 94.4% (n = 68/72) in the placebo arm. In patients with TILs-positive tumors, enrichment for clinical benefit on the buparlisib arm was seen in those with PIK3 pathway activation [25.0% (n = 17/68)] with a hazard ratio (HR) for death of 0.43 [95% confidence interval (CI) 0.21-0.87, p = 0.016]. Similarly, improved OS was seen in patients on the buparlisib arm and NOTCH pathway activation [20.5% (n = 14/68)] with a HR for death of 0.40 (95% CI 0.18-0.90, p = 0.022). Both associations were absent in the placebo group. TP53 and tumor mutational burden (TMB) did not correlate with OS in the buparlisib or placebo arms.</p><p><strong>Conclusions: </strong>In this immunogenomic analysis of BERIL-1, improved HRs for OS were seen in patients with tumor immune infiltration and selected oncogenic alterations, including PIK3 and NOTCH pathway activation (NCT01852292).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study.\",\"authors\":\"Antoine Desilets, Justin Lucas, Lisa F Licitra, Sunny Lu, Archie Tse, Tom Tang, Kevin Dreyer, Nanhai He, Lars E Birgerson, Sandrine Faivre, Denis Soulières\",\"doi\":\"10.1007/s11523-024-01126-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>BERIL-1 was a randomized phase 2 study that studied paclitaxel with either buparlisib, a pan-class I PIK3 inhibitor, or placebo in patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Considering the therapeutic paradigm shift with immune checkpoint inhibitors (ICIs) now approved in the first-line setting, we present an updated immunogenomic analysis of patients enrolled in BERIL-1, including patients with immune-infiltrated tumors.</p><p><strong>Objective: </strong>The objective of this study was to identify biomarkers predictive of treatment efficacy in the context of the post-ICI therapeutic landscape.</p><p><strong>Patients and methods: </strong>Genomic analyses were performed at baseline on tumor and/or plasma circulating DNA (ctDNA) samples, and immunohistochemistry (IHC) studies, including immune infiltration [tumor-infiltrating lymphocytes (TILs) and CD8 expression], were performed on tumor samples. Immunogenomic biomarkers were correlated to overall survival (OS).</p><p><strong>Results: </strong>Among 158 patients enrolled in BERIL-1, either tumor (53.2%; n = 84) or ctDNA samples (70.8%; n = 112) were available in 85.4% (n = 135). The most commonly mutated genes were TP53 (57.0%), NOTCH1 (23.7%), and PIK3CA (22.2%). In the IHC studies, 98.6% (n = 68/69) of patients were TILs positive in the buparlisib arm versus 94.4% (n = 68/72) in the placebo arm. In patients with TILs-positive tumors, enrichment for clinical benefit on the buparlisib arm was seen in those with PIK3 pathway activation [25.0% (n = 17/68)] with a hazard ratio (HR) for death of 0.43 [95% confidence interval (CI) 0.21-0.87, p = 0.016]. Similarly, improved OS was seen in patients on the buparlisib arm and NOTCH pathway activation [20.5% (n = 14/68)] with a HR for death of 0.40 (95% CI 0.18-0.90, p = 0.022). Both associations were absent in the placebo group. TP53 and tumor mutational burden (TMB) did not correlate with OS in the buparlisib or placebo arms.</p><p><strong>Conclusions: </strong>In this immunogenomic analysis of BERIL-1, improved HRs for OS were seen in patients with tumor immune infiltration and selected oncogenic alterations, including PIK3 and NOTCH pathway activation (NCT01852292).</p>\",\"PeriodicalId\":22195,\"journal\":{\"name\":\"Targeted Oncology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-01-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Targeted Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11523-024-01126-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Targeted Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11523-024-01126-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study.
Background: BERIL-1 was a randomized phase 2 study that studied paclitaxel with either buparlisib, a pan-class I PIK3 inhibitor, or placebo in patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Considering the therapeutic paradigm shift with immune checkpoint inhibitors (ICIs) now approved in the first-line setting, we present an updated immunogenomic analysis of patients enrolled in BERIL-1, including patients with immune-infiltrated tumors.
Objective: The objective of this study was to identify biomarkers predictive of treatment efficacy in the context of the post-ICI therapeutic landscape.
Patients and methods: Genomic analyses were performed at baseline on tumor and/or plasma circulating DNA (ctDNA) samples, and immunohistochemistry (IHC) studies, including immune infiltration [tumor-infiltrating lymphocytes (TILs) and CD8 expression], were performed on tumor samples. Immunogenomic biomarkers were correlated to overall survival (OS).
Results: Among 158 patients enrolled in BERIL-1, either tumor (53.2%; n = 84) or ctDNA samples (70.8%; n = 112) were available in 85.4% (n = 135). The most commonly mutated genes were TP53 (57.0%), NOTCH1 (23.7%), and PIK3CA (22.2%). In the IHC studies, 98.6% (n = 68/69) of patients were TILs positive in the buparlisib arm versus 94.4% (n = 68/72) in the placebo arm. In patients with TILs-positive tumors, enrichment for clinical benefit on the buparlisib arm was seen in those with PIK3 pathway activation [25.0% (n = 17/68)] with a hazard ratio (HR) for death of 0.43 [95% confidence interval (CI) 0.21-0.87, p = 0.016]. Similarly, improved OS was seen in patients on the buparlisib arm and NOTCH pathway activation [20.5% (n = 14/68)] with a HR for death of 0.40 (95% CI 0.18-0.90, p = 0.022). Both associations were absent in the placebo group. TP53 and tumor mutational burden (TMB) did not correlate with OS in the buparlisib or placebo arms.
Conclusions: In this immunogenomic analysis of BERIL-1, improved HRs for OS were seen in patients with tumor immune infiltration and selected oncogenic alterations, including PIK3 and NOTCH pathway activation (NCT01852292).
期刊介绍：
Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes:
Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches.
Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways.
Current Opinion articles that place interesting areas in perspective.
Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations.
Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement.
Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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