Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study.

IF 4.4 3区医学 Q2 ONCOLOGY Targeted Oncology Pub Date : 2025-01-14 DOI:10.1007/s11523-024-01126-0

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":"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":"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).","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}

引用次数: 0

Abstract

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).

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

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

背景：BERIL-1是一项随机2期研究，研究了紫杉醇与泛I类PIK3抑制剂buparisib或安慰剂在复发或转移（R/M）头颈部鳞状细胞癌（HNSCC）患者中的应用。考虑到免疫检查点抑制剂（ICIs）治疗模式的转变，我们提出了BERIL-1患者的最新免疫基因组学分析，包括免疫浸润性肿瘤患者。目的：本研究的目的是确定在ici后治疗环境下预测治疗效果的生物标志物。患者和方法：在基线时对肿瘤和/或血浆循环DNA （ctDNA）样本进行基因组分析，并对肿瘤样本进行免疫组织化学（IHC）研究，包括免疫浸润[肿瘤浸润淋巴细胞（TILs）和CD8表达]。免疫基因组生物标志物与总生存期（OS）相关。结果：在158例BERIL-1患者中，任一肿瘤（53.2%）；n = 84)或ctDNA样本(70.8%；N = 112)，占85.4% （N = 135）。最常见的突变基因是TP53（57.0%）、NOTCH1（23.7%）和PIK3CA（22.2%）。在免疫组化研究中，buparisib组98.6% （n = 68/69）的患者TILs阳性，而安慰剂组94.4% （n = 68/72）的患者TILs阳性。在tils阳性肿瘤患者中，PIK3通路激活的患者buparisib组的临床获益增加[25.0% (n = 17/68)]，死亡风险比（HR）为0.43[95%置信区间（CI） 0.21-0.87, p = 0.016]。同样，buparisib组患者的OS改善，NOTCH通路激活[20.5% (n = 14/68)]，死亡风险比为0.40 （95% CI 0.18-0.90, p = 0.022）。这两种关联在安慰剂组中都不存在。在布帕利西布组和安慰剂组中，TP53和肿瘤突变负荷（TMB）与OS无关。结论：在BERIL-1的免疫基因组分析中，在肿瘤免疫浸润和选择性致癌改变（包括PIK3和NOTCH通路激活（NCT01852292））的患者中，OS的hr得到改善。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

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.