Journal of Chemical & Engineering Data最新文献

{"title":"Bridging the Gap in Cancer Clinical Trial Funding.","authors":"Yara Abdou, Norman E Sharpless","doi":"10.1200/JCO-24-01484","DOIUrl":"10.1200/JCO-24-01484","url":null,"abstract":"","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3887-3890"},"PeriodicalIF":42.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data.","authors":"Georgina V Long, Evan J Lipson, F Stephen Hodi, Paolo A Ascierto, James Larkin, Christopher Lao, Jean-Jacques Grob, Flavia Ejzykowicz, Andriy Moshyk, Viviana Garcia-Horton, Zheng-Yi Zhou, Yiqiao Xin, Jennell Palaia, Laura McDonald, Sarah Keidel, Anthony Salvatore, Divya Patel, Leon A Sakkal, Hussein Tawbi, Dirk Schadendorf","doi":"10.1200/JCO.24.01125","DOIUrl":"10.1200/JCO.24.01125","url":null,"abstract":"<p><strong>Purpose: </strong>Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial.</p><p><strong>Methods: </strong>Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory.</p><p><strong>Results: </strong>After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, <i>BRAF</i>-mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% <i>v</i> 61%) and any-grade TRAEs leading to discontinuation (17% <i>v</i> 41%).</p><p><strong>Conclusion: </strong>Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.</p>","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3926-3934"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Access to Patient-Focused, Decentralized Clinical Trials Requires Streamlined Regulatory Requirements: An ASCO Research Statement.","authors":"Ramya Thota, Patricia A Hurley, Therica M Miller, Suanna S Bruinooge, Craig Lipset, R Donald Harvey, Lora J Black, Amanda Dinsdale, Janette K Merrill, Teri Pollastro, Sheila A Prindiville, Mujahid A Rizvi, Shimere Sherwood, Grzegorz S Nowakowski","doi":"10.1200/JCO.24.00961","DOIUrl":"10.1200/JCO.24.00961","url":null,"abstract":"<p><p>Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders. ASCO held multistakeholder meetings with leaders in oncology research and concluded that research-related regulatory and administrative requirements and burdens present critical barriers to decentralizing trials. One example is sponsor and contract research organization (CRO) use of US Food and Drug Administration (FDA)'s Statement of Investigator (Form 1572), which was found to exceed FDA's stated intent and used in conservative ways disproportionate to potential risks to participants and scientific integrity. As a result, research sites experience an avalanche of downstream administrative and regulatory activities that consume considerable resources. This statement recommends four key solutions to address such barriers and recalibrate regulatory and administrative expectations for decentralizing trials: (1) FDA should engage the research community in a public-private partnership to modernize standards and enable local access to trials; (2) sponsors and CROs should develop standards and protocols that accommodate flexible approaches, enable local participation, provide clarity around roles and requirements, and promote consistency; (3) research centers, networks, and sites should update policies and procedures to implement decentralized trial elements; and (4) research community should develop a streamlined, uniform mechanism to simplify regulatory data collection and documentation and use it consistently across trials. We can and must prioritize a concerted commitment to simplify and streamline regulatory requirements and practices to broaden access to and participation in cancer clinical trials.</p>","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3986-3995"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extent of Lymphadenectomy for Surgical Management of Right-Sided Colon Cancer: The Randomized Phase III RELARC Trial.","authors":"Junyang Lu, Jiadi Xing, Lu Zang, Chenghai Zhang, Lai Xu, Guannan Zhang, Zirui He, Yueming Sun, Yifei Feng, Xiaohui Du, Shidong Hu, Pan Chi, Ying Huang, Ziqiang Wang, Ming Zhong, Aiwen Wu, Anlong Zhu, Fei Li, Jianmin Xu, Liang Kang, Jian Suo, Haijun Deng, Yingjiang Ye, Kefeng Ding, Tao Xu, Yuelun Zhang, Zhongtao Zhang, Minhua Zheng, Xiangqian Su, Yi Xiao","doi":"10.1200/JCO.24.00393","DOIUrl":"10.1200/JCO.24.00393","url":null,"abstract":"<p><strong>Purpose: </strong>Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME.</p><p><strong>Methods: </strong>This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS).</p><p><strong>Results: </strong>Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] <i>v</i> D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; <i>P</i> = .06; 86.1% in the CME group <i>v</i> 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; <i>P</i> = .17; 94.7% in the CME group <i>v</i> 92.6% in the D2 group).</p><p><strong>Conclusion: </strong>This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.</p>","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3957-3966"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for <i>PIK3CA</i>-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer.","authors":"Komal L Jhaveri, Melissa K Accordino, Philippe L Bedard, Andrés Cervantes, Valentina Gambardella, Erika Hamilton, Antoine Italiano, Kevin Kalinsky, Ian E Krop, Mafalda Oliveira, Peter Schmid, Cristina Saura, Nicholas C Turner, Andrea Varga, Sravanthi Cheeti, Stephanie Hilz, Katherine E Hutchinson, Yanling Jin, Stephanie Royer-Joo, Ubong Peters, Noopur Shankar, Jennifer L Schutzman, Dejan Juric","doi":"10.1200/JCO.24.00110","DOIUrl":"10.1200/JCO.24.00110","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of inavolisib, a potent and selective small-molecule inhibitor of p110α that promotes the degradation of mutated p110α, in combination with palbociclib and endocrine therapy (ET), in a phase I/Ib study in patients with <i>PIK3CA</i>-mutated, hormone receptor-positive/human epidermal growth factor receptor 2-negative locally advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT03006172).</p><p><strong>Methods: </strong>Women ≥18 years of age received inavolisib, palbociclib, and letrozole (Inavo + Palbo + Letro arm) or fulvestrant (Inavo + Palbo + Fulv arm) until unacceptable toxicity or disease progression. The primary objective was to evaluate safety or tolerability.</p><p><strong>Results: </strong>Fifty-three patients were included, 33 in the Inavo + Palbo + Letro arm and 20 in the Inavo + Palbo + Fulv arm. Median duration of inavolisib treatment was 15.7 and 20.8 months (cutoff: March 27, 2023), respectively. Treatment-related adverse events (TRAEs) occurred in all patients; the most frequent were stomatitis, hyperglycemia, and diarrhea; grade ≥3 any TRAE rates were 87.9% and 85.0%; 6.1% and 10.0% discontinued any treatment due to TRAEs in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. No PK drug-drug interactions (DDIs) were observed among the study treatments when administered. Confirmed objective response rates were 52.0% and 40.0% in patients with measurable disease, and median progression-free survival was 23.3 and 35.0 months in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. Available paired pre- and on-treatment tumor tissue and circulating tumor DNA analyses confirmed the effects of study treatment on pharmacodynamic and pathophysiologic biomarkers of response.</p><p><strong>Conclusion: </strong>Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity.</p>","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3947-3956"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to B. Tombal et al.","authors":"David J Einstein, Meredith M Regan, Julia S Stevens, David F McDermott, Ravi A Madan","doi":"10.1200/JCO-24-01595","DOIUrl":"10.1200/JCO-24-01595","url":null,"abstract":"","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3997-3998"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility of Circulating Tumor DNA Assays.","authors":"Steven Sorscher","doi":"10.1200/JCO.24.01175","DOIUrl":"10.1200/JCO.24.01175","url":null,"abstract":"","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3998-3999"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlative Science in the Cooperative Group System: Re-Engineering for Success.","authors":"Peter J O'Dwyer, Norman Wolmark, Douglas S Hawkins, Mitchell Schnall, Janet Dancey, Charles Blanke, Robert Mannel, Evanthia Galanis, Quynh-Thu Le","doi":"10.1200/JCO.24.00527","DOIUrl":"10.1200/JCO.24.00527","url":null,"abstract":"","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3905-3910"},"PeriodicalIF":42.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma.","authors":"Pedro Barata, Catherine Tangen, Melissa Plets, Ian M Thompson, Vivek Narayan, Daniel J George, Daniel Y C Heng, Brian Shuch, Mark Stein, Shuchi Gulati, Maria Tretiakova, Abhishek Tripathi, Georg A Bjarnason, Peter Humphrey, Adebowale Adeniran, Ulka Vaishampayan, Ajjai Alva, Tian Zhang, Scott Cole, Primo N Lara, Seth P Lerner, Naomi Balzer-Haas, Sumanta K Pal","doi":"10.1200/JCO.24.00767","DOIUrl":"10.1200/JCO.24.00767","url":null,"abstract":"<p><p><i>Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in</i> JCO <i>or elsewhere, for which the primary end point has already been reported.</i>Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized phase II, open-label trial, 147 patients with advanced PRCC who have received up to one previous therapy (excluding vascular endothelial growth factor-directed agents) were assigned to sunitinib, cabozantinib, crizotinib, or savolitinib. Ultimately, savolitinib and crizotinib arms were closed because of futility. With a median follow-up of 17.5 months, the median OS was 21.5 months (95% CI, 12.0 to 28.1) with cabozantinib and 17.3 months (95% CI, 12.8 to 21.8) with sunitinib (hazard ratio, 0.83; 95% CI, 0.51 to 1.36; <i>P</i> = .46). The OS landmark estimates for cabozantinib and sunitinib were 50% versus 39% at 24 months and 32% versus 28% at 36 months. In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease.</p>","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3911-3916"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease.","authors":"Vijaya Raj Bhatt, Valerie K Shostrom, Hannah K Choe, Betty K Hamilton, Krishna Gundabolu, Lori J Maness, Virender Kumar, Ram I Mahato, Lynette M Smith, Taiga Nishihori, Stephanie J Lee","doi":"10.1200/JCO.24.00205","DOIUrl":"10.1200/JCO.24.00205","url":null,"abstract":"<p><strong>Purpose: </strong>Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD.</p><p><strong>Patients and methods: </strong>In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria.</p><p><strong>Results: </strong>Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals.</p><p><strong>Conclusion: </strong>The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.</p>","PeriodicalId":42,"journal":{"name":"Journal of Chemical & Engineering Data","volume":" ","pages":"3977-3985"},"PeriodicalIF":2.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}