Pub Date : 2024-11-01Epub Date: 2024-08-05DOI: 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.
{"title":"Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238.","authors":"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","doi":"10.1200/JCO.23.01448","DOIUrl":"10.1200/JCO.23.01448","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Patients and methods: </strong>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] <i>v</i> >12 months [late] from initial therapy).</p><p><strong>Results: </strong>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% <i>v</i> 31%); median OS was 19.8 versus 42.8 months (24-month rates: 37% <i>v</i> 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.</p><p><strong>Conclusion: </strong>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.</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/PMC11527380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893516","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}
Pub Date : 2024-11-01Epub Date: 2024-05-17DOI: 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.
{"title":"Avoiding Delays in Reporting Time-to-Event Randomized Trials: Calendar Backstops and Other Approaches.","authors":"Megan Othus, Boris Freidlin, Edward L Korn","doi":"10.1200/JCO.24.00025","DOIUrl":"10.1200/JCO.24.00025","url":null,"abstract":"<p><p>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.</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/PMC11521763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957337","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}
Pub Date : 2024-11-01Epub Date: 2024-10-01DOI: 10.1200/JCO-24-01758
Theodoros Karantanos, Tania Jain
{"title":"Battle of the Sexes in the Clonal World.","authors":"Theodoros Karantanos, Tania Jain","doi":"10.1200/JCO-24-01758","DOIUrl":"10.1200/JCO-24-01758","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":"142365392","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}
Pub Date : 2024-11-01Epub Date: 2024-06-27DOI: 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.
{"title":"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.","authors":"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","doi":"10.1200/JCO.23.02170","DOIUrl":"10.1200/JCO.23.02170","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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% <i>v</i> 81.8%, hazard ratio [HR], 0.10, <i>P</i> = .01) and iDFS (96.3% <i>v</i> 81.8%, HR, 0.20, <i>P</i> = .047) among patients with HER2DX low-risk versus high-risk tumors, respectively.</p><p><strong>Conclusion: </strong>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.</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/PMC11527383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468361","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}
Pub Date : 2024-11-01Epub Date: 2024-08-02DOI: 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}
Pub Date : 2024-11-01Epub Date: 2024-07-24DOI: 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?
{"title":"On the Strength of a Recommendation.","authors":"Michael Sanatani","doi":"10.1200/JCO.24.01054","DOIUrl":"10.1200/JCO.24.01054","url":null,"abstract":"<p><p>Can an oncologist doing shared decision making connect with patients via treatment recommendations?</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":"141758971","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}
Pub Date : 2024-11-01Epub Date: 2023-11-06DOI: 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 theASCO 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).
{"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}
Pub Date : 2024-11-01Epub Date: 2024-07-02DOI: 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.
{"title":"Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.","authors":"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","doi":"10.1200/JCO.24.00020","DOIUrl":"10.1200/JCO.24.00020","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Patients and methods: </strong>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).</p><p><strong>Results: </strong>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/m<sup>2</sup> 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.</p><p><strong>Conclusion: </strong>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.</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/PMC11521759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492179","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}
Pub Date : 2024-11-01Epub Date: 2024-07-30DOI: 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}