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Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238. CheckMate 238 中已切除黑色素瘤辅助检查点抑制剂治疗后的复发后系统治疗效果。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-05 DOI: 10.1200/JCO.23.01448
Jeffrey Weber, Michele Del Vecchio, Mario Mandalá, Helen Gogas, Ana M Arance, Stephane Dalle, C Lance Cowey, Michael Schenker, Jean-Jacques Grob, Vanna Chiarion-Sileni, Iván Márquez-Rodas, Marcus O Butler, Anna Maria Di Giacomo, Luis de la Cruz-Merino, Petr Arenberger, Victoria Atkinson, Andrew Hill, Leslie A Fecher, Michael Millward, Nikhil I Khushalani, Paola Queirolo, Georgina V Long, Maurice Lobo, Margarita Askelson, Paolo A Ascierto, James Larkin

Purpose: In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy.

Patients and methods: Patients 15 years or older with resected stage IIIB-C/IV melanoma were stratified by stage and tumor PD-L1 status and randomly assigned to receive nivolumab 3 mg/kg every 2 weeks, or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks for 1 year or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Patients with recurrence in each group were assessed for PFS and OS from subsequent systemic therapy (SST) initiation per recurrence timing (≤12 months [early] v >12 months [late] from initial therapy).

Results: Recurrences occurred in 198 (44%) of 453 nivolumab-treated patients (122 early, 76 late) and 232 (51%) of 453 ipilimumab-treated patients (160 early, 72 late). Median PFS on next-line systemic therapy for nivolumab-treated patients recurring early versus late was 4.7 versus 12.4 months (24-month rates, 16% v 31%); median OS was 19.8 versus 42.8 months (24-month rates: 37% v 73%). In response to subsequent therapy, patients on nivolumab with late versus early recurrence were more likely to benefit from anti-PD-1 monotherapy. Nivolumab-treated patients with either an early or late recurrence benefitted from an ipilimumab-based therapy or targeted therapy, each with similar OS.

Conclusion: Postrecurrence survival was longer for patients who recurred >12 months. Patients on nivolumab who recurred early benefitted from SST but had better survival with ipilimumab-based regimens or targeted therapy compared with anti-PD-1 monotherapy.

目的:在III期CheckMate 238中,在切除的IIIB-C/IV期黑色素瘤患者中,与伊匹单抗相比,nivolumab辅助治疗可显著改善无复发生存期,但总生存期(OS)无明显差异。在此,我们研究了复发后系统治疗后的无进展生存期(PFS)和OS:15岁或15岁以上切除的IIIB-C/IV期黑色素瘤患者按分期和肿瘤PD-L1状态进行分层,随机分配接受尼妥珠单抗3 mg/kg,每2周一次,或伊匹单抗10 mg/kg,每3周一次,共4次,然后每12周一次,持续1年或直到疾病复发、出现不可接受的毒性或撤回同意。根据复发时间(初始治疗后≤12个月[早期]v >12个月[晚期])评估各组复发患者自后续系统治疗(SST)开始的PFS和OS:453名接受过尼伐单抗治疗的患者中有198人(44%)复发(122人早期复发,76人晚期复发),453名接受过伊匹单抗治疗的患者中有232人(51%)复发(160人早期复发,72人晚期复发)。早期复发与晚期复发的nivolumab治疗患者接受下一步系统治疗的中位PFS分别为4.7个月和12.4个月(24个月的比例为16%和31%);中位OS分别为19.8个月和42.8个月(24个月的比例为37%和73%)。在后续治疗方面,接受尼妥珠单抗治疗的晚期复发患者比早期复发患者更有可能从抗PD-1单药治疗中获益。接受尼妥珠单抗治疗的早期或晚期复发患者均可从基于伊匹单抗的治疗或靶向治疗中获益,两者的OS相似:结论:复发时间大于12个月的患者的复发后生存期更长。接受尼妥珠单抗治疗的早期复发患者可从SST中获益,但与抗PD-1单药治疗相比,以伊匹单抗为基础的治疗方案或靶向治疗的生存率更高。
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引用次数: 0
Avoiding Delays in Reporting Time-to-Event Randomized Trials: Calendar Backstops and Other Approaches. 避免事件时间随机试验报告的延迟:日历逆止器及其他方法。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-05-17 DOI: 10.1200/JCO.24.00025
Megan Othus, Boris Freidlin, Edward L Korn

New oncology therapies that extend patients' lives beyond initial expectations and improving later-line treatments can lead to complications in clinical trial design and conduct. In particular, for trials with event-based analyses, the time to observe all the protocol-specified events can exceed the finite follow-up of a clinical trial or can lead to much delayed release of outcome data. With the advent of multiple classes of oncology therapies leading to much longer survival than in the past, this issue in clinical trial design and conduct has become increasingly important in recent years. We propose a straightforward prespecified backstop rule for trials with a time-to-event analysis and evaluate the impact of the rule with both simulated and real-world trial data. We then provide recommendations for implementing the rule across a range of oncology clinical trial settings.

新的肿瘤疗法能延长患者的生命,超出最初的预期,并能改善后期治疗,这可能会导致临床试验的设计和实施复杂化。特别是对于基于事件分析的试验,观察所有方案指定事件的时间可能会超过临床试验的有限随访时间,或导致结果数据的发布大大延迟。随着多类肿瘤疗法的出现,患者的生存期比过去大大延长,近年来临床试验设计和实施中的这一问题变得越来越重要。我们为采用时间到事件分析的试验提出了一个简单明了的预设后备规则,并通过模拟和实际试验数据评估了该规则的影响。然后,我们提出了在一系列肿瘤临床试验中实施该规则的建议。
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引用次数: 0
Battle of the Sexes in the Clonal World. 克隆世界的性别之战
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-01 DOI: 10.1200/JCO-24-01758
Theodoros Karantanos, Tania Jain
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引用次数: 0
Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT. 人类表皮生长因子受体 2 阳性乳腺癌 I 期曲妥珠单抗 Emtansine 与紫杉醇加曲妥珠单抗的辅助治疗:ATEMPT 的 5 年结果和相关分析。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-27 DOI: 10.1200/JCO.23.02170
Paolo Tarantino, Nabihah Tayob, Guillermo Villacampa, Chau Dang, Denise A Yardley, Steven J Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Douglas Weckstein, Antonio C Wolff, Katherine Reeder-Hayes, Hope S Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna K Gadi, Michael Constantine, Kit Cheng, Audrey Merrill Garrett, P Kelly Marcom, Kathy Albain, Patricia DeFusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel C Jankowitz, Mothaffar Rimawi, Vandana Abramson, Paula R Pohlmann, Catherine Van Poznak, Andres Forero-Torres, Minetta C Liu, Kathryn J Ruddy, Adrienne G Waks, Michelle DeMeo, Harold J Burstein, Ann H Partridge, Patrizia Dell'Orto, Leila Russo, Emma Krause, Daniel J Newhouse, Busem Binboğa Kurt, Elizabeth A Mittendorf, Bryan Schneider, Aleix Prat, Eric P Winer, Ian E Krop, Sara M Tolaney

Purpose: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

Methods: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia.

Results: After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). At 5 years, the recurrence-free interval (RFI) was 98.3% (95% CI, 97.0 to 99.7), the overall survival was 97.8% (95% CI, 96.3 to 99.3), and the breast cancer-specific survival was 99.4% (95% CI, 98.6 to 100). Comparable iDFS was observed with T-DM1 irrespective of tumor size, hormone receptor status, centrally determined HER2 immunohistochemical score, and receipt of T-DM1 for more or less than 6 months. Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%. Among patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes significantly differed according to HER2DX risk score, with better RFI (98.1% v 81.8%, hazard ratio [HR], 0.10, P = .01) and iDFS (96.3% v 81.8%, HR, 0.20, P = .047) among patients with HER2DX low-risk versus high-risk tumors, respectively.

Conclusion: Adjuvant T-DM1 for 1 year leads to outstanding long-term outcomes for patients with stage I HER2-positive breast cancer. A high HER2DX risk score predicted a higher risk of recurrence in ATEMPT.

目的:I期人类表皮生长因子受体2(HER2)阳性乳腺癌患者接受曲妥珠单抗依姆坦辛(T-DM1)辅助治疗后的长期预后仍未确定,预后预测指标是一项尚未满足的需求:在ATEMPT II期试验中,经中心确诊为HER2阳性的I期乳腺癌患者以3:1的比例随机分配接受为期一年的T-DM1辅助治疗或紫杉醇加曲妥珠单抗(TH)治疗。主要目的是比较两组患者临床相关毒性反应的发生率,并评估T-DM1的侵袭性无病生存期(iDFS)。相关分析包括HER2DX基因组工具、HER2异质性的多组学评估以及血小板减少的预测因素:中位随访5.8年后,T-DM1组观察到11例iDFS事件,5年iDFS为97.0%(95% CI,95.2-98.7)。5年无复发间隔(RFI)为98.3%(95% CI,97.0至99.7),总生存率为97.8%(95% CI,96.3至99.3),乳腺癌特异性生存率为99.4%(95% CI,98.6至100)。无论肿瘤大小、激素受体状态、中心测定的HER2免疫组化评分以及接受T-DM1治疗的时间长于或短于6个月,都能观察到与T-DM1相似的iDFS。虽然 ATEMPT 没有为这一终点提供动力,但 TH 治疗组的 5 年 iDFS 为 91.1%。在有足够组织进行HER2DX检测的患者(n = 187)中,根据HER2DX风险评分,5年结果有显著差异,HER2DX低风险与高风险肿瘤患者的RFI(98.1% v 81.8%,危险比[HR],0.10,P = .01)和iDFS(96.3% v 81.8%,HR,0.20,P = .047)分别更好:结论:对I期HER2阳性乳腺癌患者进行为期1年的T-DM1辅助治疗可获得良好的长期疗效。高HER2DX风险评分预示着ATEMPT的复发风险较高。
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引用次数: 0
Targeting EWS::FLI1 to Advance Ewing Sarcoma Therapy. 靶向 EWS::FLI1 推进尤文肉瘤治疗
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-11 DOI: 10.1200/JCO-24-01323
Caterina Mancarella, Katia Scotlandi
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引用次数: 0
Sex-Based Differences in Risk of Therapy-Related Myeloid Neoplasms. 治疗相关髓细胞肿瘤风险的性别差异
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-02 DOI: 10.1200/JCO-24-01487
Melissa A Richard, Chengcheng Yan, Yanjun Chen, Christopher J Gibson, Rashi Kalra, Alysia Bosworth, David K Crossman, Purnima Singh, Lindsey Hageman, Jianbo He, Saro H Armenian, Julie Vose, Daniel J Weisdorf, Benjamin L Ebert, Yutaka Yasui, Changde Cheng, Stephen J Forman, Smita Bhatia, Ravi Bhatia

Purpose: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell (PBSC) transplantation for non-Hodgkin lymphoma (NHL). Previous studies report an association between clonal hematopoiesis (CH) in PBSC and risk of t-MN, but small samples precluded examination of risk within specific subpopulations.

Methods: Targeted DNA sequencing was performed to identify CH mutations in PBSC from a retrospective cohort of 984 patients with NHL (median age at transplant, 57 years; range, 18-78). Fine-Gray proportional subdistribution hazard regression models estimated association between number of CH mutations and t-MN, adjusting for demographic, clinical, and therapeutic variables. Secondary analyses evaluated the association between CH and t-MN among males and females.

Results: CH was identified in PBSC from 366 patients (37.2%). t-MN developed in 60 patients after a median follow-up of 5 years. Presence of ≥2 mutations conferred increased t-MN risk (adjusted hazard ratio [aHR], 2.10; 95% CI [1.08 to 4.11]; P = .029). CH was associated with increased t-MN risk among males (aHR, 1.83 [95% CI, 1.01 to 3.31]) but not females (aHR, 0.56 [95% CI, 0.15 to 2.09]). Although the prevalence and type of CH mutations in PBSC were comparable, the 8-year cumulative incidence of t-MN was higher among males vs. females with CH (12.4% v 3.6%) but was similar between males and females without CH (4.9% v 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males.

Conclusion: presence of CH mutations in PBSC confers increased risk of t-MN after autologous transplantation in male but not female patients with NHL. Factors underlying sex-based differences in risk of CH progression to t-MN merit further investigation.

背景:治疗相关髓样肿瘤(t-MN)是自体外周血干细胞(PBSC)移植治疗非霍奇金淋巴瘤(NHL)的一种威胁生命的并发症。先前的研究报告称,PBSC中的克隆造血(CH)与t-MN风险之间存在关联,但由于样本较少,无法对特定亚人群的风险进行检测:方法:对984名NHL患者(移植时中位年龄为57岁;范围:18-78岁)的PBSC进行靶向DNA测序,以确定CH突变。细灰比例亚分布危险回归模型估计了CH突变数量与t-MN之间的关系,并对人口统计学、临床和治疗变量进行了调整。二次分析评估了CH与男性和女性t-MN之间的关系:中位随访5年后,60名患者出现了t-MN。出现≥2个突变会增加t-MN风险(调整后危险比[aHR]=2.10,95%置信区间[CI]=1.08-4.11,P=0.029)。CH与男性(aHR=1.83,95%CI=1.01-3.31)而非女性(aHR=0.56,95%CI=0.15-2.09)的t-MN风险增加有关。虽然PBSC中CH突变的发生率和类型相当,但男性与女性CH患者8年的t-MN累积发生率更高(12.4% vs. 3.6%),但男性与女性无CH患者的t-MN累积发生率相似(4.9% vs. 3.9%)。PBSC中的CH克隆扩增到t-MN仅见于男性:结论:PBSC中存在CH突变会增加男性NHL患者自体移植后出现t-MN的风险,但不会增加女性NHL患者自体移植后出现t-MN的风险。CH进展为t-MN风险的性别差异因素值得进一步研究。
{"title":"Sex-Based Differences in Risk of Therapy-Related Myeloid Neoplasms.","authors":"Melissa A Richard, Chengcheng Yan, Yanjun Chen, Christopher J Gibson, Rashi Kalra, Alysia Bosworth, David K Crossman, Purnima Singh, Lindsey Hageman, Jianbo He, Saro H Armenian, Julie Vose, Daniel J Weisdorf, Benjamin L Ebert, Yutaka Yasui, Changde Cheng, Stephen J Forman, Smita Bhatia, Ravi Bhatia","doi":"10.1200/JCO-24-01487","DOIUrl":"10.1200/JCO-24-01487","url":null,"abstract":"<p><strong>Purpose: </strong>Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell (PBSC) transplantation for non-Hodgkin lymphoma (NHL). Previous studies report an association between clonal hematopoiesis (CH) in PBSC and risk of t-MN, but small samples precluded examination of risk within specific subpopulations.</p><p><strong>Methods: </strong>Targeted DNA sequencing was performed to identify CH mutations in PBSC from a retrospective cohort of 984 patients with NHL (median age at transplant, 57 years; range, 18-78). Fine-Gray proportional subdistribution hazard regression models estimated association between number of CH mutations and t-MN, adjusting for demographic, clinical, and therapeutic variables. Secondary analyses evaluated the association between CH and t-MN among males and females.</p><p><strong>Results: </strong>CH was identified in PBSC from 366 patients (37.2%). t-MN developed in 60 patients after a median follow-up of 5 years. Presence of ≥2 mutations conferred increased t-MN risk (adjusted hazard ratio [aHR], 2.10; 95% CI [1.08 to 4.11]; <i>P</i> = .029). CH was associated with increased t-MN risk among males (aHR, 1.83 [95% CI, 1.01 to 3.31]) but not females (aHR, 0.56 [95% CI, 0.15 to 2.09]). Although the prevalence and type of CH mutations in PBSC were comparable, the 8-year cumulative incidence of t-MN was higher among males vs. females with CH (12.4% <i>v</i> 3.6%) but was similar between males and females without CH (4.9% <i>v</i> 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males.</p><p><strong>Conclusion: </strong>presence of CH mutations in PBSC confers increased risk of t-MN after autologous transplantation in male but not female patients with NHL. Factors underlying sex-based differences in risk of CH progression to t-MN merit further investigation.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878776","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
On the Strength of a Recommendation. 建议的力量
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-24 DOI: 10.1200/JCO.24.01054
Michael Sanatani

Can an oncologist doing shared decision making connect with patients via treatment recommendations?

进行共同决策的肿瘤医生能否通过治疗建议与患者建立联系?
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引用次数: 0
Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Rapid Recommendation Update. 177Lutetum-PSMA-617治疗转移性Castion-耐药前列腺癌症的系统治疗更新:ASCO指南快速推荐更新。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2023-11-06 DOI: 10.1200/JCO.23.02128
Rohan Garje, R Bryan Rumble, Rahul A Parikh

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).

ASCO快速建议更新强调了对ASCO指南建议的修订,以应对新数据和实践变化数据的出现。快速更新得到证据审查的支持,并遵循ASCO指南方法手册中概述的指南制定过程。这些文章的目的是及时传播最新的建议,更好地向卫生从业者和公众提供癌症最佳治疗方案。指南和更新不旨在取代治疗提供者的独立专业判断,也不考虑患者之间的个体差异。免责声明和其他重要信息见附录(附录1和附录2,仅在线)。
{"title":"Systemic Therapy Update on <sup>177</sup>Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Rapid Recommendation Update.","authors":"Rohan Garje, R Bryan Rumble, Rahul A Parikh","doi":"10.1200/JCO.23.02128","DOIUrl":"10.1200/JCO.23.02128","url":null,"abstract":"<p><p><i>ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the</i> <i>ASCO Guideline Methodology Manual</i><i>. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).</i></p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481981","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
Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma. TK216:第一代EWS::FLI1融合蛋白拮抗剂治疗尤文肉瘤。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-02 DOI: 10.1200/JCO.24.00020
Paul A Meyers, Noah Federman, Najat Daw, Peter M Anderson, Lara E Davis, AeRang Kim, Margaret E Macy, Angela Pietrofeso, Ravin Ratan, Richard F Riedel, Matteo Trucco, James B Breitmeyer, Jeffrey A Toretsky, Joseph A Ludwig

Purpose: Ewing Sarcoma (ES), a rare cancer with a pathognomonic translocation resulting in the Ewing sarcoma gene (EWS)::FLI1 oncoprotein, has a poor prognosis in the relapsed/refractory (R/R) setting. Tokalas (TK)216 was designed to bind EWS::FLI1 proteins directly, disrupt protein-protein interactions, and inhibit transcription factor function. TK216 plus vincristine showed synergistic activity in preclinical tumor models. To our knowledge, we report the results of a first-in-class, first-in-human phase I/II trial of TK216 in R/R ES.

Patients and methods: TK216 was administered intravenously as a continuous infusion to patients with R/R ES in 11 cohorts. The dosing duration of 7 days was later extended to 10, 14, and 28 days. Vincristine could be added on day 1 after cycle 2, per investigators' choice. The trial used a 3 + 3 design with an expansion cohort at the recommended phase II dose (RP2D).

Results: A total of 85 patients with a median age of 27 years (range, 11-77) were enrolled. The maximum tolerated dose for the 14-day infusion of TK216, 200 mg/m2 once daily, was determined in cohort 9 and selected as the RP2D. The median previous number of systemic therapies regimens was three (range, 1-10). The most frequent-related adverse events in patients treated at the RP2D included neutropenia (44.7%), anemia (29.4%), leukopenia (29.4%), febrile neutropenia (15.3%), thrombocytopenia (11.8%), and infections (17.6%). In cohorts 9 and 10, two patients had a complete response, one had a partial response, and 14 had stable disease; the 6-month progression-free survival was 11.9%. There were no responses among the eight patients in cohort 11.

Conclusion: TK216 administered as 14-day continuous infusion with or without vincristine was well tolerated and showed limited activity at the RP2D in R/R ES.

目的:尤文肉瘤(ES)是一种罕见的癌症,其病理标志性易位导致尤文肉瘤基因(EWS)::FLI1 肿瘤蛋白,在复发/难治(R/R)情况下预后较差。Tokalas (TK)216旨在直接结合EWS::FLI1蛋白,破坏蛋白与蛋白之间的相互作用,抑制转录因子的功能。TK216 加长春新碱在临床前肿瘤模型中显示出协同活性。据我们所知,我们报告了TK216在R/R ES中的首次同类、首次人体I/II期试验结果:TK216以连续输注的方式静脉给药给11组R/R ES患者。用药时间从 7 天延长至 10 天、14 天和 28 天。根据研究者的选择,长春新碱可在第2周期后的第1天加入。试验采用3+3设计,并按II期推荐剂量(RP2D)扩增队列:共有85名患者入组,中位年龄为27岁(11-77岁)。第9队列确定了14天输注TK216的最大耐受剂量(200 mg/m2,每日一次),并将其选定为RP2D。既往接受过全身治疗方案的中位数为3次(1-10次不等)。在RP2D治疗的患者中,最常见的相关不良事件包括中性粒细胞减少(44.7%)、贫血(29.4%)、白细胞减少(29.4%)、发热性中性粒细胞减少(15.3%)、血小板减少(11.8%)和感染(17.6%)。在第9组和第10组中,2名患者完全应答,1名患者部分应答,14名患者病情稳定;6个月无进展生存率为11.9%。第11组的8名患者没有应答:结论:TK216与长春新碱或不与长春新碱一起连续输注14天,耐受性良好,在R/R ES的RP2D显示出有限的活性。
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引用次数: 0
Rectal Relief: Proton Therapy's Impact on Urgency and Frequency. 直肠舒缓:质子疗法对尿急和尿频的影响
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-30 DOI: 10.1200/JCO.24.01162
Omran Saifi, Albert Attia, Bradford S Hoppe
{"title":"Rectal Relief: Proton Therapy's Impact on Urgency and Frequency.","authors":"Omran Saifi, Albert Attia, Bradford S Hoppe","doi":"10.1200/JCO.24.01162","DOIUrl":"10.1200/JCO.24.01162","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855582","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
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Journal of Clinical Oncology
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