Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study

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

A. van Ommen-Nijhof , T.G. Steenbruggen , T.G. Wiersma , S. Balduzzi , A. Daletzakis , M.J. Holtkamp , M. Delfos , M. Schot , K. Beelen , E.J.M. Siemerink , J. Heijns , I.A. Mandjes , J. Wesseling , E.H. Rosenberg , M.J.T. Vrancken Peeters , S.C. Linn , G.S. Sonke

{"title":"Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study","authors":"A. van Ommen-Nijhof , T.G. Steenbruggen , T.G. Wiersma , S. Balduzzi , A. Daletzakis , M.J. Holtkamp , M. Delfos , M. Schot , K. Beelen , E.J.M. Siemerink , J. Heijns , I.A. Mandjes , J. Wesseling , E.H. Rosenberg , M.J.T. Vrancken Peeters , S.C. Linn , G.S. Sonke","doi":"10.1016/j.ejca.2024.115083","DOIUrl":null,"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":"213 ","pages":"Article 115083"},"PeriodicalIF":7.6000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804924012140","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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

查看原文本刊更多论文

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

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

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分钟内获得全文求助全文

来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.