European Journal of Cancer最新文献

{"title":"16S rRNA target sequencing of human tumors validates findings of Lachnoclostridium abundance in human melanomas that are heavily CD8+ T-cell infiltrated.","authors":"Lingeng Lu, Caroline Johnson, Sajid Khan, Harriet Kluger","doi":"10.1016/j.ejca.2024.115084","DOIUrl":"https://doi.org/10.1016/j.ejca.2024.115084","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544530","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}

{"title":"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.","authors":"Anna Kron, Matthias Scheffler, Juergen Wolf","doi":"10.1016/j.ejca.2024.115086","DOIUrl":"https://doi.org/10.1016/j.ejca.2024.115086","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557480","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}

{"title":"Resection of colorectal liver metastases with second-line aflibercept plus FOLFIRI: Results from the RESECTION prospective French cohort","authors":"David Tougeron ,&nbsp;Frederic Bibeau ,&nbsp;Benoist Chibaudel ,&nbsp;Stefano Kim ,&nbsp;Thierry Nguyen ,&nbsp;Jean-Marc Phelip ,&nbsp;Dominique Mille ,&nbsp;Mohamed Bouattour ,&nbsp;David Tavan ,&nbsp;Yves Rinaldi ,&nbsp;Thierry Lecomte ,&nbsp;Hervé Perrier ,&nbsp;Dominique Spaeth ,&nbsp;François-Xavier Caroli Bosc ,&nbsp;Jean-Philippe Metges ,&nbsp;Marc Ferec ,&nbsp;Vincent Hautefeuille ,&nbsp;Marion Deslandres-Cruchant ,&nbsp;Jerome Danion ,&nbsp;Pascal Hammel ,&nbsp;René Adam","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 &lt;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 &lt; 0.0001) and PFS (median 11.4 vs 4.9 months, p &lt; 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}

{"title":"Classic Hodgkin Lymphoma: The LYSA pragmatic guidelines","authors":"Cédric Rossi ,&nbsp;Guillaume Manson ,&nbsp;Amira Marouf ,&nbsp;Aurélie Cabannes-Hamy ,&nbsp;Emmanuelle Nicolas-Virelizier ,&nbsp;Marie Maerevoet ,&nbsp;Marion Alcantara ,&nbsp;Lysiane Molina ,&nbsp;Antony Ceraulo ,&nbsp;Marilyne Poirée ,&nbsp;Jean Galtier ,&nbsp;Nadia Diop ,&nbsp;Caroline Delette ,&nbsp;Amandine Segot ,&nbsp;Sydney Dubois ,&nbsp;Agathe Waultier ,&nbsp;Sophie Bernard ,&nbsp;Robin Noël ,&nbsp;Stéphanie Guidez ,&nbsp;Milena Kohn ,&nbsp;Hervé Ghesquières","doi":"10.1016/j.ejca.2024.115073","DOIUrl":"10.1016/j.ejca.2024.115073","url":null,"abstract":"<div><div>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.</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":"142593609","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}

{"title":"Assessing the real-world effectiveness of 8 major metastatic breast cancer drugs using target trial emulation","authors":"Alison Antoine ,&nbsp;David Pérol ,&nbsp;Mathieu Robain ,&nbsp;Thomas Bachelot ,&nbsp;Rémy Choquet ,&nbsp;William Jacot ,&nbsp;Béchir Ben Hadj Yahia ,&nbsp;Thomas Grinda ,&nbsp;Suzette Delaloge ,&nbsp;Christine Lasset ,&nbsp;Youenn Drouet","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}

{"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 ,&nbsp;T.G. Steenbruggen ,&nbsp;T.G. Wiersma ,&nbsp;S. Balduzzi ,&nbsp;A. Daletzakis ,&nbsp;M.J. Holtkamp ,&nbsp;M. Delfos ,&nbsp;M. Schot ,&nbsp;K. Beelen ,&nbsp;E.J.M. Siemerink ,&nbsp;J. Heijns ,&nbsp;I.A. Mandjes ,&nbsp;J. Wesseling ,&nbsp;E.H. Rosenberg ,&nbsp;M.J.T. Vrancken Peeters ,&nbsp;S.C. Linn ,&nbsp;G.S. Sonke","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}

{"title":"Immune marker expression and prognosis of early breast cancer expressing HER3","authors":"Dae-Won Lee ,&nbsp;Han Suk Ryu ,&nbsp;Ilias P. Nikas ,&nbsp;Jiwon Koh ,&nbsp;Tae-Yong Kim ,&nbsp;Hong Kyu Kim ,&nbsp;Han-Byoel Lee ,&nbsp;Hyeong-Gon Moon ,&nbsp;Wonshik Han ,&nbsp;Kyung-Hun Lee ,&nbsp;Seock-Ah Im","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}

{"title":"Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival","authors":"Kazumasa Fujitani ,&nbsp;Yukinori Kurokawa ,&nbsp;Ryohei Wada ,&nbsp;Atsushi Takeno ,&nbsp;Ryohei Kawabata ,&nbsp;Takeshi Omori ,&nbsp;Hiroshi Imamura ,&nbsp;Motohiro Hirao ,&nbsp;Shunji Endo ,&nbsp;Junji Kawada ,&nbsp;Jeong Ho Moon ,&nbsp;Shuji Takiguchi ,&nbsp;Masaki Mori ,&nbsp;Hidetoshi Eguchi ,&nbsp;Yuichiro Doki ,&nbsp;on behalf of the Osaka University Clinical Research Group for Gastroenterological Surgery","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}

{"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":"Simeone D’Ambrosio ,&nbsp;Fabio Salomone ,&nbsp;Filippo Vitale ,&nbsp;Annarita Avanzo ,&nbsp;Angela Viggiano ,&nbsp;Luigi Liguori ,&nbsp;Roberto Ferrara ,&nbsp;Antonio Nuccio ,&nbsp;Giuseppe Viscardi ,&nbsp;Fabiana Napolitano ,&nbsp;Antonio Santaniello ,&nbsp;Luigi Formisano ,&nbsp;Roberto Bianco ,&nbsp;Alberto Servetto","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_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.</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; 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.</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}

{"title":"Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study","authors":"Arun A. Azad ,&nbsp;Karim Fizazi ,&nbsp;Nobuaki Matsubara ,&nbsp;Fred Saad ,&nbsp;Ugo De Giorgi ,&nbsp;Jae Young Joung ,&nbsp;Peter C.C. Fong ,&nbsp;Robert J. Jones ,&nbsp;Stefanie Zschäbitz ,&nbsp;Jan Oldenburg ,&nbsp;Neal D. Shore ,&nbsp;Curtis Dunshee ,&nbsp;Joan Carles ,&nbsp;Andre P. Fay ,&nbsp;Xun Lin ,&nbsp;Liza DeAnnuntis ,&nbsp;Nicola Di Santo ,&nbsp;Michael A. Zielinski ,&nbsp;Neeraj Agarwal","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}