European Journal of Cancer最新文献_第2页

16S rRNA target sequencing of human tumors validates findings of Lachnoclostridium abundance in human melanomas that are heavily CD8+ T-cell infiltrated. 人类肿瘤的 16S rRNA 目标测序验证了在 CD8+ T 细胞大量浸润的人类黑色素瘤中大量存在拉氏梭菌的结论。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-24 DOI: 10.1016/j.ejca.2024.115084

Lingeng Lu, Caroline Johnson, Sajid Khan, Harriet Kluger

引用次数: 0

Response to letter entitled: Re: Indirect comparison of capmatinib treatment from GEOMETRY mono-1 trial to SOC in German patients with locally advanced or metastatic NSCLC harboring METex14 skipping mutations. 对题为Re：在德国携带 METex14 跳过突变的局部晚期或转移性 NSCLC 患者中，将 GEOMETRY mono-1 试验中的卡马替尼治疗与 SOC 进行间接比较。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-24 DOI: 10.1016/j.ejca.2024.115086

Anna Kron, Matthias Scheffler, Juergen Wolf

引用次数: 0

Resection of colorectal liver metastases with second-line aflibercept plus FOLFIRI: Results from the RESECTION prospective French cohort 结直肠肝转移灶切除术与二线aflibercept加FOLFIRI疗法：法国前瞻性队列RESECTION的研究结果

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-22 DOI: 10.1016/j.ejca.2024.115082

Aim

To evaluate R0/R1 resection rate in patients with colorectal liver metastases (CLM) treated with aflibercept plus FOLFIRI after failure of a prior oxaliplatin-based regimen in daily clinical practice.

Methods

This French, multicentre, prospective, observational cohort (NCT05178745) included patients with CLM (alone or predominant; up to 5 lung nodules <2 cm allowed) initiating aflibercept plus FOLFIRI every 2 weeks per physician choice. Primary endpoint was R0/R1 resection rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), radiological and pathological responses, and safety.

Results

A total of 137 patients (median age 65 years, RAS/BRAF mutant 57 %/9 %) were enrolled at 22 French sites. CLM (median 4) were synchronous in 82 %, bilobar in 71 % and located in liver only in 54 %. Overall, 17 % of patients had R0/R1 resection (21 % for patients with liver-only disease). A major pathological response per Blazer score was observed in 55 % of resected patients, along with significantly longer OS (median 34.8 vs 9.1 months, p < 0.0001) and PFS (median 11.4 vs 4.9 months, p < 0.0001) compared to non-resected patients. Post-operative complications occurred in 17 % of patients (all Dindo-Clavien grade I-II) and there was no post-operative deaths. Overall, 34 % had grade ≥ 3 adverse events, mainly general health deterioration and diarrhea.

Conclusions

Results suggest that aflibercept plus FOLFIRI, after failure of a prior oxaliplatin-based regimen, allows R0/R1 resection of CLM in almost 20 % of patients with a major pathological response in most cases and a median OS prolonged by more than 3-fold versus non-resected patients.

方法这项法国多中心、前瞻性、观察性队列研究（NCT05178745）纳入了结直肠肝转移（CLM）患者（单独或主要；最多允许5个肺结节<2 cm），根据医生的选择，每2周开始一次aflibercept加FOLFIRI治疗。主要终点是R0/R1切除率。次要终点包括总生存期（OS）、无进展生存期（PFS）、放射学和病理学反应以及安全性。结果共有137名患者（中位年龄65岁，RAS/BRAF突变57%/9%）在22个法国研究机构接受了治疗。82%的CLM（中位数为4）为同步，71%为双叶，54%仅位于肝脏。总体而言，17%的患者进行了R0/R1切除术（21%的患者只切除了肝脏）。根据 Blazer 评分，55% 的切除患者有主要病理反应，与未切除患者相比，OS（中位 34.8 个月 vs 9.1 个月，p < 0.0001）和 PFS（中位 11.4 个月 vs 4.9 个月，p < 0.0001）显著延长。17%的患者出现术后并发症（均为丁多-克拉维恩 I-II 级），无术后死亡病例。总的来说，34%的患者出现了≥3级的不良反应，主要是全身健康状况恶化和腹泻。结论结果表明，在既往奥沙利铂方案治疗失败后，aflibercept加FOLFIRI可使近20%的CLM患者进行R0/R1切除，大多数病例可获得主要病理反应，与未切除患者相比，中位OS延长了3倍以上。

{"title":"Resection of colorectal liver metastases with second-line aflibercept plus FOLFIRI: Results from the RESECTION prospective French cohort","authors":"","doi":"10.1016/j.ejca.2024.115082","DOIUrl":"10.1016/j.ejca.2024.115082","url":null,"abstract":"<div><h3>Aim</h3><div>To evaluate R0/R1 resection rate in patients with colorectal liver metastases (CLM) treated with aflibercept plus FOLFIRI after failure of a prior oxaliplatin-based regimen in daily clinical practice.</div></div><div><h3>Methods</h3><div>This French, multicentre, prospective, observational cohort (NCT05178745) included patients with CLM (alone or predominant; up to 5 lung nodules <2 cm allowed) initiating aflibercept plus FOLFIRI every 2 weeks per physician choice. Primary endpoint was R0/R1 resection rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), radiological and pathological responses, and safety.</div></div><div><h3>Results</h3><div>A total of 137 patients (median age 65 years, <em>RAS/BRAF</em> mutant 57 %/9 %) were enrolled at 22 French sites. CLM (median 4) were synchronous in 82 %, bilobar in 71 % and located in liver only in 54 %. Overall, 17 % of patients had R0/R1 resection (21 % for patients with liver-only disease). A major pathological response per Blazer score was observed in 55 % of resected patients, along with significantly longer OS (median 34.8 vs 9.1 months, p < 0.0001) and PFS (median 11.4 vs 4.9 months, p < 0.0001) compared to non-resected patients. Post-operative complications occurred in 17 % of patients (all Dindo-Clavien grade I-II) and there was no post-operative deaths. Overall, 34 % had grade ≥ 3 adverse events, mainly general health deterioration and diarrhea.</div></div><div><h3>Conclusions</h3><div>Results suggest that aflibercept plus FOLFIRI, after failure of a prior oxaliplatin-based regimen, allows R0/R1 resection of CLM in almost 20 % of patients with a major pathological response in most cases and a median OS prolonged by more than 3-fold versus non-resected patients.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Classic Hodgkin Lymphoma: The LYSA pragmatic guidelines 典型霍奇金淋巴瘤：LYSA 实用指南

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-22 DOI: 10.1016/j.ejca.2024.115073

Classic Hodgkin lymphoma (HL) is a distinct entity among hematological malignancies of B-cell origin. It is characterized by its unique histopathological features and generally favorable prognosis. Over the years, advancements in understanding its pathogenesis, coupled with refined diagnostic and evaluation modalities, as well as therapeutic strategies, have significantly transformed the landscape of HL management. In this article, we present a comprehensive set of recommendations for the management of HL, encompassing various aspects of diagnosis, risk stratification, evaluation, and treatment. These recommendations are based on the latest evidence-based guidelines, expert consensus opinions, and clinical trial data, aiming to provide clinicians with a practical framework for delivering optimal care to patients with HL.

经典霍奇金淋巴瘤（HL）是 B 细胞来源血液恶性肿瘤中的一种独特类型。它具有独特的组织病理学特征，预后一般良好。多年来，随着对其发病机制认识的不断深入、诊断和评估方法的不断完善以及治疗策略的不断改进，HL 的治疗格局发生了显著变化。在本文中，我们为 HL 的治疗提出了一套全面的建议，包括诊断、风险分层、评估和治疗等各个方面。这些建议基于最新的循证指南、专家共识意见和临床试验数据，旨在为临床医生提供一个切实可行的框架，为 HL 患者提供最佳治疗。

引用次数: 0

Assessing the real-world effectiveness of 8 major metastatic breast cancer drugs using target trial emulation 利用靶向试验模拟评估 8 种主要转移性乳腺癌药物的实际疗效。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-22 DOI: 10.1016/j.ejca.2024.115072

Background

Demonstration of trial emulation ability to benchmark randomised controlled trials (RCTs) from real-world data (RWD) is required to increase confidence in the use of routinely collected data for decision making in oncology.

Methods

To assess the frequency with which emulation findings align with RCTs regarding effect size on overall survival (OS) in metastatic breast cancer (MBC), 8 of 13 pre-selected pivotal RCTs in MBC were emulated using data from 32,598 patients enrolled in the French ESME-MBC cohort between January 1, 2008 and December 31, 2021. Adjustment methods and confounders were selected a priori for each emulation; stabilized weight was the reference method to mitigate confounding. Concordance in OS hazard ratios with associated 95 % confidence intervals between RCTs and emulations were assessed used predefined metrics based on statistical significance, estimates, and standardized differences.

Results

The effect sizes were consistent with RCT results in 7 out of the 8 emulations; 4 emulations achieved full statistical significance agreement; 5 emulations had a point estimate included in the RCT CI (estimate agreement); 6 emulations reported no significant differences between RCT and emulation (standardized difference agreement). Discrepancies related to residual confounders and significant shifts in prescription practices post-drug approval may arise in some cases.

Conclusion

Target trial emulation from RWD combined with appropriate adjustment can provide conclusions similar to RCTs in MBC. In oncology, this methodology offers opportunities for confirming the impact on long-term survival, for expanding indications in patients excluded from RCTs and for comparative effectiveness in single-arm trials using external control arms.

背景：需要展示试验仿真能力，以真实世界数据（RWD）作为随机对照试验（RCT）的基准，从而增强人们对使用常规收集的数据进行肿瘤决策的信心：为了评估在转移性乳腺癌（MBC）总生存期（OS）效应大小方面仿真结果与RCT一致的频率，我们利用2008年1月1日至2021年12月31日期间入组法国ESME-MBC队列的32598名患者的数据，对13项预选的MBC关键RCT中的8项进行了仿真。每次模拟都事先选择了调整方法和混杂因素；稳定权重是减轻混杂因素的参考方法。使用基于统计显著性、估计值和标准化差异的预定指标，评估了RCT与模拟之间OS危险比及相关95%置信区间的一致性：在 8 个仿真结果中，有 7 个仿真结果的效应大小与 RCT 结果一致；有 4 个仿真结果的统计显著性完全一致；有 5 个仿真结果的点估计值包含在 RCT CI 中（估计值一致）；有 6 个仿真结果显示 RCT 与仿真结果之间无显著差异（标准化差异一致）。在某些情况下，可能会出现与残余混杂因素和药物批准后处方做法的重大变化有关的差异：结论：RWD 的目标试验仿真结合适当的调整，可以在 MBC 中得出与 RCT 相似的结论。在肿瘤学领域，这种方法可用于确认对长期生存的影响、扩大被 RCT 排除在外的患者的适应症以及在使用外部对照臂的单臂试验中进行疗效比较。

{"title":"Assessing the real-world effectiveness of 8 major metastatic breast cancer drugs using target trial emulation","authors":"","doi":"10.1016/j.ejca.2024.115072","DOIUrl":"10.1016/j.ejca.2024.115072","url":null,"abstract":"<div><h3>Background</h3><div>Demonstration of trial emulation ability to benchmark randomised controlled trials (RCTs) from real-world data (RWD) is required to increase confidence in the use of routinely collected data for decision making in oncology.</div></div><div><h3>Methods</h3><div>To assess the frequency with which emulation findings align with RCTs regarding effect size on overall survival (OS) in metastatic breast cancer (MBC), 8 of 13 pre-selected pivotal RCTs in MBC were emulated using data from 32,598 patients enrolled in the French ESME-MBC cohort between January 1, 2008 and December 31, 2021. Adjustment methods and confounders were selected <em>a priori</em> for each emulation; stabilized weight was the reference method to mitigate confounding. Concordance in OS hazard ratios with associated 95 % confidence intervals between RCTs and emulations were assessed used predefined metrics based on statistical significance, estimates, and standardized differences.</div></div><div><h3>Results</h3><div>The effect sizes were consistent with RCT results in 7 out of the 8 emulations; 4 emulations achieved full statistical significance agreement; 5 emulations had a point estimate included in the RCT CI (estimate agreement); 6 emulations reported no significant differences between RCT and emulation (standardized difference agreement). Discrepancies related to residual confounders and significant shifts in prescription practices post-drug approval may arise in some cases.</div></div><div><h3>Conclusion</h3><div>Target trial emulation from RWD combined with appropriate adjustment can provide conclusions similar to RCTs in MBC. In oncology, this methodology offers opportunities for confirming the impact on long-term survival, for expanding indications in patients excluded from RCTs and for comparative effectiveness in single-arm trials using external control arms.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study 对携带同源重组缺陷的寡转移性乳腺癌患者进行强化烷化化疗：随机III期OLIGO研究的主要结果

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-20 DOI: 10.1016/j.ejca.2024.115083

Background

Oligometastatic breast cancer (OMBC) is a clinical entity with a prospect of long-term survival, but uncertainty remains on its optimal treatment. We studied whether intensified alkylating chemotherapy (IACT) improves long-term outcome compared to conventional-dose chemotherapy (CDCT) as part of a multimodality approach for patients with OMBC harboring homologous recombination deficiency (HRD).

Patients and methods

Eligible patients had HER2-negative OMBC, harboring HRD, with ≤ 3 distant metastases, pathologic proof of distant disease and a favorable response to three cycles CDCT. Participants were randomized 1:1 to continue with either CDCT or IACT. IACT consisted of one mobilization course followed by two cycles of mini-CTC (carboplatin, thiotepa and cyclophosphamide) supported by peripheral blood progenitor cell reinfusion. Primary outcome was event-free survival (EFS). Secondary endpoints included overall survival (OS), quality of life and safety.

Results

Seventy-five patients were randomized to either IACT (n = 36) or CDCT (n = 39). Twenty-three (31 %) patients had hormone receptor-positive disease and 52 (69 %) had triple-negative disease. Median EFS in the IACT-group was 28 months (95 % confidence interval [CI] 21-not reached [NR]) versus 25 months (95 %CI 14-NR) in the CDCT-group (hazard ratio [HR] for recurrence or death 0.78, 95 %CI 0.42–1.42). Median OS was 67 months (95 %CI 37-NR) in the IACT-group and 36 (95 %CI 26-NR) in the CDCT-group (HR 0.74, 95 %CI 0.37–1.48).

Conclusions

The entire study population experienced long-term survival, with median OS well over five years. IACT compared to CDCT did not improve outcome in patients with OMBC harboring study-defined HRD. The optimal therapy for patients with OMBC requires further study.

Trial Registration

ClinicalTrials.gov: NCT01646034

背景转移性乳腺癌（OMBC）是一种具有长期生存前景的临床实体，但其最佳治疗方法仍不确定。我们研究了与常规剂量化疗（CDCT）相比，强化烷化化疗（IACT）作为多模式疗法的一部分，是否能改善携带同源重组缺陷（HRD）的OMBC患者的长期预后。患者和方法符合条件的患者为HER2阴性OMBC，携带HRD，远处转移灶≤3个，病理证明有远处疾病，对三个周期的CDCT有良好反应。参试者按1:1比例随机选择继续接受CDCT或IACT治疗。IACT包括一个动员疗程，然后是两个周期的迷你CTC（卡铂、硫替帕和环磷酰胺），并辅以外周血祖细胞再灌注。主要结果是无事件生存期（EFS）。结果75名患者随机接受了IACT（36人）或CDCT（39人）治疗。23名患者（31%）激素受体阳性，52名患者（69%）三阴性。IACT组的中位生存期为28个月（95%置信区间[CI] 21-未达[NR]），而CDCT组为25个月（95%CI 14-NR）（复发或死亡危险比[HR]0.78，95%CI 0.42-1.42）。IACT 组的中位 OS 为 67 个月（95 %CI 37-NR），CDCT 组为 36 个月（95 %CI 26-NR）（HR 0.74，95 %CI 0.37-1.48）。与CDCT相比，IACT并不能改善研究定义的HRD的OMBC患者的预后。OMBC患者的最佳疗法需要进一步研究：NCT01646034

{"title":"Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study","authors":"","doi":"10.1016/j.ejca.2024.115083","DOIUrl":"10.1016/j.ejca.2024.115083","url":null,"abstract":"<div><h3>Background</h3><div>Oligometastatic breast cancer (OMBC) is a clinical entity with a prospect of long-term survival, but uncertainty remains on its optimal treatment. We studied whether intensified alkylating chemotherapy (IACT) improves long-term outcome compared to conventional-dose chemotherapy (CDCT) as part of a multimodality approach for patients with OMBC harboring homologous recombination deficiency (HRD).</div></div><div><h3>Patients and methods</h3><div>Eligible patients had HER2-negative OMBC, harboring HRD, with ≤ 3 distant metastases, pathologic proof of distant disease and a favorable response to three cycles CDCT. Participants were randomized 1:1 to continue with either CDCT or IACT. IACT consisted of one mobilization course followed by two cycles of mini-CTC (carboplatin, thiotepa and cyclophosphamide) supported by peripheral blood progenitor cell reinfusion. Primary outcome was event-free survival (EFS). Secondary endpoints included overall survival (OS), quality of life and safety.</div></div><div><h3>Results</h3><div>Seventy-five patients were randomized to either IACT (n = 36) or CDCT (n = 39). Twenty-three (31 %) patients had hormone receptor-positive disease and 52 (69 %) had triple-negative disease. Median EFS in the IACT-group was 28 months (95 % confidence interval [CI] 21-not reached [NR]) versus 25 months (95 %CI 14-NR) in the CDCT-group (hazard ratio [HR] for recurrence or death 0.78, 95 %CI 0.42–1.42). Median OS was 67 months (95 %CI 37-NR) in the IACT-group and 36 (95 %CI 26-NR) in the CDCT-group (HR 0.74, 95 %CI 0.37–1.48).</div></div><div><h3>Conclusions</h3><div>The entire study population experienced long-term survival, with median OS well over five years. IACT compared to CDCT did not improve outcome in patients with OMBC harboring study-defined HRD. The optimal therapy for patients with OMBC requires further study.</div></div><div><h3>Trial Registration</h3><div>ClinicalTrials.gov: NCT01646034</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune marker expression and prognosis of early breast cancer expressing HER3 表达 HER3 的早期乳腺癌的免疫标记表达和预后。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-20 DOI: 10.1016/j.ejca.2024.115081

Introduction

There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established.

Methods

The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive.

Results

Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % vs. 85.2 %, p = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor.

Conclusions

This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising.

导言：以 HER3 为靶点有很强的合理性，因为 HER3 会导致肿瘤发生和耐药性。然而，HER3的预后作用及其与免疫调节蛋白表达的关联尚未确定：本研究的主要目的是研究 HER3 表达的预后作用，并根据 HER3 状态确定免疫调节标志物的表达。2008年，在首尔国立大学医院接受根治性手术的320名I-III期乳腺癌患者中，HER3表达和10种免疫调节蛋白（PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4）表达得到了确认。中位随访时间为 88.8 个月。HER3 IHC 的标准采用 HER2 IHC 的评分，只有 3 + 的患者才被视为阳性：在 320 例患者中，213 例（67.2%）为管腔 A 型疾病，30 例（9.5%）为管腔 B 型疾病，28 例（8.8%）为 HER2 阳性疾病，46 例（14.5%）为三阴性疾病。153名患者（47.8%）有HER3表达。与HER3阴性肿瘤相比，HER3表达的肿瘤具有更强的免疫原性肿瘤微环境。此外，与 HER3 阴性患者相比，HER3 表达患者的 5 年无复发生存率更高（5 年 RFS 92.5% 对 85.2%，P = 0.038）。然而，在多变量分析中，HER3表达不是预后因素，但免疫调节蛋白的表达是预后因素：这项研究根据乳腺癌患者的 HER3 状态确定了免疫调节蛋白的表达。由于HER3表达的肿瘤具有更强的免疫原性微环境，研究HER3靶向药物和免疫疗法联合治疗HER3表达的乳腺癌可能很有前景。

{"title":"Immune marker expression and prognosis of early breast cancer expressing HER3","authors":"","doi":"10.1016/j.ejca.2024.115081","DOIUrl":"10.1016/j.ejca.2024.115081","url":null,"abstract":"<div><h3>Introduction</h3><div>There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established.</div></div><div><h3>Methods</h3><div>The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive.</div></div><div><h3>Results</h3><div>Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % <em>vs.</em> 85.2 %, <em>p</em> = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor.</div></div><div><h3>Conclusions</h3><div>This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival 胃癌肝转移手术切除的前瞻性单臂多中心介入研究；3年总生存期和无复发生存期。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-20 DOI: 10.1016/j.ejca.2024.115080

Objective

Potential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study.

Methods

Patients with synchronous or metachronous LMGC received 2–4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis.

Results

Seventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1–71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9–34.0) and 34.9 % (95 % CI 22.2–50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1–3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16–6.35), P = 0.022; pN1–3: HR 9.11 (95 % CI, 1.22–68.2), P = 0.031).

Conclusion

R0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. Clinical trial registration number: UMIN 000011445 (https://www.umin.ac.jp/ctr/).

目的：手术切除胃癌肝转移灶（LMGC）的潜在益处仍存在争议，因为之前的研究多为回顾性研究。我们在一项前瞻性单臂多中心干预研究中评估了化疗后手术切除 LMGC 的疗效：同步或近交LMGC患者接受2-4个周期的标准化疗，如果重新分期显示疾病无进展并有机会进行R0切除，则进行手术切除。主要终点是R0患者的3年OS，RFS为次要终点。R0患者的预后因素通过多变量Cox回归分析进行评估：2011年至2019年期间，共有70名患者入组。2名患者不符合条件，20名患者在手术前中止了治疗。在最终接受手术的48名患者中，43人完成了原发性和/或转移性GC的R0切除，1人完成了R2切除，4人被认为不符合条件。R0患者的中位和3年OS分别为39.8个月（95%置信区间[CI]，26.9至未达到）和58.1%（95% CI，43.1-71.8），而中位和3年RFS分别为14.9个月（95% CI 7.9-34.0）和34.9%（95% CI 22.2-50.1）。多变量分析显示，多发性肝转移和阳性结节状态（pN1-3）与OS呈负相关（多发性肝转移：危险比[HR]2.71（95 % CI，1.16-6.35），P = 0.022；pN1-3：HR 9.11（95 % CI，1.22-68.2），P = 0.031）：结论：LMGC化疗后行R0切除术可获得良好的生存率，多发肝转移和结节阳性是预后不良的重要指标：临床试验注册号：umin 000011445 (https://www.umin.ac.jp/ctr/)。

{"title":"Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival","authors":"","doi":"10.1016/j.ejca.2024.115080","DOIUrl":"10.1016/j.ejca.2024.115080","url":null,"abstract":"<div><h3>Objective</h3><div>Potential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study.</div></div><div><h3>Methods</h3><div>Patients with synchronous or metachronous LMGC received 2–4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis.</div></div><div><h3>Results</h3><div>Seventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1–71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9–34.0) and 34.9 % (95 % CI 22.2–50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1–3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16–6.35), <em>P</em> = 0.022; pN1–3: HR 9.11 (95 % CI, 1.22–68.2), <em>P</em> = 0.031).</div></div><div><h3>Conclusion</h3><div>R0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. Clinical trial registration number: UMIN 000011445 (https://www.umin.ac.jp/ctr/).</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis 晚期癌症免疫疗法 RCT 中对 PFS 的盲法独立中央审查与地方研究者评估：系统回顾与荟萃分析。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-20 DOI: 10.1016/j.ejca.2024.115077

Background

Assessment of Progression-free survival (PFS) events by investigators might be inaccurate in randomized controlled trials (RCTs) with open-label design. We explored differences in PFS evaluated by blinded independent central review (BICR) or local investigator assessment (IA) in trials testing immunotherapy (IO) in advanced cancers.

Methods

We systematically reviewed articles of RCTs investigating IO in advanced tumors, published in PubMed-indexed journals up to December 2023. For each RCT, we collected PFS results by BICR and by local IA. We calculated the discrepancy index (DI) as the ratio of BICR and IA Hazard Ratios (HR_BICR/HR_IA) for PFS. An overall DI and relative confidence interval (CI) were calculated using a fixed-effect model weighted for the inverse of variance.

Findings

Only 32/140 (22.9 %) RCTs reported both BICR and local IA PFS data, including 17,054 patients. PFS was the sole primary endpoint in 19/32 (59.4 %) and a co-primary endpoint 9/32 (28.2 %) trials. The study design was open label or double-blind in 17/32 (53.1 %) and 15/32 (46.9 %) RCTs, respectively. The overall DI was 1.07 (95 % CI 1.01–1.13; I² =0, p = 0.02), revealing a more optimistic analysis of results in favor of local IA. In the 17 open-label trials, the overall DI was 1.09 (95 % CI 1.02–1.17, I2 =0, p = 0.02), revealing a more favorable interpretation of PFS results by local investigators.

Interpretation

We found a statistically significant difference between BICR and local IA of PFS in trials of IO in cancer. These results suggest that the double assessment is recommended in RCTs testing IO, especially in open-label trials.

Funding

This work was supported by the MFAG 27826–2022 grant (Dr. Alberto Servetto).

背景：在采用开放标签设计的随机对照试验（RCT）中，研究者对无进展生存期（PFS）事件的评估可能不准确。我们探讨了在晚期癌症免疫疗法（IO）试验中，通过盲法独立中央审查（BICR）或当地研究者评估（IA）对无进展生存期进行评估的差异：我们系统回顾了截至2023年12月发表在PubMed索引期刊上的研究晚期肿瘤IO的RCT文章。对于每项 RCT，我们都收集了 BICR 和当地 IA 的 PFS 结果。我们计算了差异指数（DI），即 BICR 和 IA 的 PFS 危险比（HRBICR/HRIA）。采用方差倒数加权的固定效应模型计算了总体差异指数和相对置信区间（CI）：只有 32/140 项（22.9%）研究同时报告了 BICR 和局部 IA PFS 数据，包括 17,054 名患者。PFS是19/32（59.4%）项试验的唯一主要终点，也是9/32（28.2%）项试验的共同主要终点。17/32（53.1%）和15/32（46.9%）项RCT的研究设计分别为开放标签或双盲。总体DI为1.07 (95 % CI 1.01-1.13; I2 =0, p = 0.02)，显示出更乐观的结果分析有利于局部IA。在17项开放标签试验中，总的DI为1.09（95 % CI 1.02-1.17，I2 =0，P = 0.02），显示当地研究者对PFS结果的解释更为有利：我们发现，在癌症 IO 试验中，BICR 和当地 IA 对 PFS 的判定在统计学上存在显著差异。这些结果表明，在进行IO试验的RCT中，尤其是在开放标签试验中，建议进行双重评估：这项工作得到了 MFAG27826-2022 基金（Alberto Servetto 博士）的支持。

{"title":"Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.ejca.2024.115077","DOIUrl":"10.1016/j.ejca.2024.115077","url":null,"abstract":"<div><h3>Background</h3><div>Assessment of Progression-free survival (PFS) events by investigators might be inaccurate in randomized controlled trials (RCTs) with open-label design. We explored differences in PFS evaluated by blinded independent central review (BICR) or local investigator assessment (IA) in trials testing immunotherapy (IO) in advanced cancers.</div></div><div><h3>Methods</h3><div>We systematically reviewed articles of RCTs investigating IO in advanced tumors, published in PubMed-indexed journals up to December 2023. For each RCT, we collected PFS results by BICR and by local IA. We calculated the discrepancy index (DI) as the ratio of BICR and IA Hazard Ratios (HR<sub>BICR</sub>/HR<sub>IA</sub>) for PFS. An overall DI and relative confidence interval (CI) were calculated using a fixed-effect model weighted for the inverse of variance.</div></div><div><h3>Findings</h3><div>Only 32/140 (22.9 %) RCTs reported both BICR and local IA PFS data, including 17,054 patients. PFS was the sole primary endpoint in 19/32 (59.4 %) and a co-primary endpoint 9/32 (28.2 %) trials. The study design was open label or double-blind in 17/32 (53.1 %) and 15/32 (46.9 %) RCTs, respectively. The overall DI was 1.07 (95 % CI 1.01–1.13; I<sup>2</sup> =0, p = 0.02), revealing a more optimistic analysis of results in favor of local IA. In the 17 open-label trials, the overall DI was 1.09 (95 % CI 1.02–1.17, I2 =0, p = 0.02), revealing a more favorable interpretation of PFS results by local investigators.</div></div><div><h3>Interpretation</h3><div>We found a statistically significant difference between BICR and local IA of PFS in trials of IO in cancer. These results suggest that the double assessment is recommended in RCTs testing IO, especially in open-label trials.</div></div><div><h3>Funding</h3><div>This work was supported by the <span>MFAG</span> <span><span>27826–2022</span></span> grant (Dr. Alberto Servetto).</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study 他唑帕利联合恩杂鲁胺治疗转移性耐受性前列腺癌：随机、安慰剂对照、III 期 TALAPRO-2 研究的安全性分析

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-20 DOI: 10.1016/j.ejca.2024.115078

Background

This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.

Methods

The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.

Results

In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).

Conclusion

Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.

ClinicalTrials.gov Identifier

NCT03395197

背景这项详细分析进一步描述了正在进行的针对转移性耐受性前列腺癌（mCRPC）患者的随机III期TALAPRO-2研究中，talazoparib联合恩杂鲁胺的安全性特征。在全基因组和同源重组修复（HRR）缺陷人群中，与安慰剂加恩杂鲁胺相比，talazoparib加恩杂鲁胺可显著改善无放射进展生存期。方法TALAPRO-2中的他拉唑帕利+恩杂鲁胺安全人群包括队列1中的398名患者（所有来访者，未选择HRR基因改变者）和合并HRR缺陷人群中的198名患者（所有来访者中HRR基因改变者加上随后入组的HRR基因改变者；队列2）。患者接受塔拉帕利 0.5 毫克（0.35 毫克，中度肾功能损害）和恩扎鲁胺 160 毫克的治疗，每天一次。安全性分析评估了常见的治疗突发不良事件（TEAE）、其类型、严重程度、时间、严重性以及与研究治疗的关系。结果在所有患者（n = 398）和HRR缺陷人群（n = 198）中，分别有71.9%和66.2%的患者报告了使用talazoparib加恩杂鲁胺的全因3/4级（G3/4）TEAE。最常见的G3/4血液学TEAE为贫血（分别为46.7%和40.9%）、中性粒细胞减少（分别为18.3%和18.7%）和血小板减少（分别为7.3%和7.1%）。G3/4贫血症的中位发生时间分别为3.3个月和3.3个月，G3/4中性粒细胞减少症的中位发生时间分别为2.3个月和2.3个月，G3/4血小板减少症的中位发生时间分别为2.3个月和1.5个月。血红蛋白的最大降幅出现在治疗 13 周和 15 周之后。分别有18.8%和10.1%的患者停用了talazoparib。通过中断剂量（62.1%和57.6%）、减少剂量（52.8%和52.0%）、血液学支持治疗（13.1%和10.6%）和输注红细胞（39.2%和35.9%）等方法处理了TEAEs。

{"title":"Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study","authors":"","doi":"10.1016/j.ejca.2024.115078","DOIUrl":"10.1016/j.ejca.2024.115078","url":null,"abstract":"<div><h3>Background</h3><div>This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.</div></div><div><h3>Methods</h3><div>The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.</div></div><div><h3>Results</h3><div>In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).</div></div><div><h3>Conclusion</h3><div>Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.</div></div><div><h3>ClinicalTrials.gov Identifier</h3><div>NCT03395197</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0