Cancer最新文献

{"title":"Hypofractionated preoperative radiotherapy for extremity soft tissue sarcoma: Are we racing ahead of the toxicity data?","authors":"Kilian E. Salerno MD,&nbsp;Denise Reinke MS, NP, MBA,&nbsp;Kathrin Schuster,&nbsp;B. Ashleigh Guadagnolo MD, MPH","doi":"10.1002/cncr.70542","DOIUrl":"10.1002/cncr.70542","url":null,"abstract":"<p>For patients who have localized, high-risk soft tissue sarcoma of the extremity, combined-modality local treatment with radiation therapy (RT) and surgery offers high rates of local control. When RT is used, preoperative RT is recommended. The current standard of care dosing is 50 Gray (Gy) conventionally fractionated, delivered as 2 Gy per fraction for 25 fractions. Recent interest in shorter courses of preoperative RT has led to several investigations, mostly phase 2 trials, of various ultrahypofractionated and moderately hypofractionated regimens. Those studies demonstrated that, when the preoperative RT dose is estimated to be radiobiologically equivalent to or higher than the 50 Gy conventional standard, local control is commensurate. Major wound complication rates are also acceptable. Differences in toxicities with hypofractionation emerge when the daily fractional dose increases, particularly with regard to delayed wound closure beyond 180 days from surgery and amputations for treatment-related complications. Long-term assessment of bone toxicity is also warranted. A randomized controlled trial of hypofractionation versus the conventionally fractionated standard is needed and must include a composite toxicity co-primary endpoint that includes not only fibrosis, edema, and joint limitation but also delayed wound closure, fracture, and limb loss. Because local control is excellent with the current standard RT and surgery, functional and quality-of-life outcomes are paramount when assessing potential changes in RT approaches. To ensure a patient-centered approach to investigating hypofractionation for soft tissue sarcoma, patient and patient advocate perspectives should be included in clinical trial design and the selection of outcomes measures.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The weight of the enemy: Tumor burden as a tumor-agnostic prognostic marker and the limits of immunotherapy","authors":"Vivek Subbiah MD,&nbsp;Elad Sharon MD, MPH","doi":"10.1002/cncr.70556","DOIUrl":"10.1002/cncr.70556","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardization of postoperative adverse event reporting: A critical opportunity for improvement within the National Clinical Trials Network","authors":"Beth Helmink MD, PhD,&nbsp;Matthew H. G. Katz MD,&nbsp;Chandrajit P. Raut MD, MSc,&nbsp;Sumithra J. Mandrekar PhD,&nbsp;Kristina Laumann BA,&nbsp;Allison Booth MS,&nbsp;Laura Hoffman MA,&nbsp;Eric A. Singer MD, MA, MS,&nbsp;Isabelle Bedrosian MD,&nbsp;Rebecca A. Snyder MD, MPH","doi":"10.1002/cncr.70555","DOIUrl":"10.1002/cncr.70555","url":null,"abstract":"&lt;p&gt;Structured reporting of adverse events (AEs) is a central component of clinical trials, allowing for accurate evaluation of the safety and tolerability of tested therapies in patients with cancer. Currently, AEs are recorded using the Common Terminology Criteria for Adverse Events (CTCAE), a standard lexicon that provides clear definitions of discrete AEs with an associated grading system.&lt;/p&gt;&lt;p&gt;In 1979, the World Health Organization recognized the need to develop a reproducible, consistent, and readily usable AE reporting system for use in clinical trials. In response, the US National Cancer Institute (NCI) published its first version of the Common Toxicity in Cancer criteria in 1982 and a second version in 1998.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The program was then revised by the Cancer Therapy Evaluation Program of the NCI to generate the CTCAE (version 3), first published in 2003. Development of the CTCAE involved academic, governmental, and pharmaceutical industry clinical investigators, and drafts were reviewed more than twice by more than 400 reviewers. CTCAE became the new standard for all NCI-sponsored clinical trials as of October 2003 and has since been revised to its current version (version 6).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;CTCAE v.6 contains 850 discrete event items that are graded for severity on a 5-point scale according to clearly delineated clinical criteria. In addition to being required in all NCI-sponsored trials, CTCAE is now consistently used in industry-sponsored cancer trials and in clinical practice to document the extent of treatment-related toxicities. In CTCAE, AEs are categorized as: (1) laboratory-based events; (2) observable/measurable events; and (3) symptomatic events.&lt;/p&gt;&lt;p&gt;In parallel, the Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996 with the aim of standardizing and improving published reports of randomized controlled trials (RCTs). Revisions in 2001 added a single item to require reporting of AEs, which was then expanded in 2003 to include a discrete checklist of items that should be included when reporting harms in RCTs. Importantly, this checklist made a specific recommendation that trial publications should clearly document a list of AEs with standardized definitions for each; if no such definition exists, a clear description should be provided for any new definitions used in the study. When available, trial publications should also give attention to AE grading, severity, and attribution. It was also recommended that expected versus unexpected events should be reported separately. Together, the CONSORT statement and CTCAE have improved standardized reporting of treatment-related toxicities across clinical trials.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Although many clinical trials focus solely on pharmaceutical therapies, others test multidisciplinary interventions, including locoregional therapies, such as transcutaneous therapy (e.g., radiation, histotripsy), percutaneou","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70555","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early neural signatures of cancer-related fatigue: A longitudinal magnetic resonance imaging study of cortical micro- and macrostructural changes during breast cancer chemotherapy","authors":"Yanfei Zhou MS,&nbsp;Jin Liu PhD,&nbsp;Xiao Fu MS,&nbsp;Jian Fan MS,&nbsp;Zong Cao MS,&nbsp;Jing Li MS,&nbsp;Ruiping Ye PhD,&nbsp;Hongzhi Wang MS,&nbsp;Lizhuang Yang PhD,&nbsp;Hai Li PhD","doi":"10.1002/cncr.70558","DOIUrl":"10.1002/cncr.70558","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer-related fatigue is a prevalent and debilitating symptom in patients with breast cancer (BC) undergoing chemotherapy (CTx), yet its early neural correlates remain incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This longitudinal study included 61 female patients with BC and 41 healthy female controls assessed before CTx and after two cycles of CTx, or at matched intervals. Assessments included 3T brain magnetic resonance imaging, patient-reported fatigue and quality-of-life measures, clinician-rated affective symptom scales, and an objective cognitive screening measure. Surface-based analyses were used to extract cortical microstructural measures, including cortical mean diffusivity (cMD), and macrostructural measures. Linear mixed-effects models were used to examine longitudinal changes and group-by-time interaction effects in clinical, patient-reported, cognitive, and cortical structural outcomes, as well as their associations during early CTx.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During early CTx, patients with BC showed worsening fatigue and worsened emotional well-being, and changes in these outcomes were positively associated. cMD decreased over time in the left isthmus cingulate cortex, and the magnitude of this decrease was associated with worsening fatigue and worsened emotional well-being. Mediation analysis suggested an indirect association between cMD changes in this region and fatigue through worsened emotional well-being.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that early increases in fatigue during CTx are linked to worsening emotional well-being and region-specific cortical microstructural changes. The results highlight a potentially informative neural-affective pathway in the early emergence of fatigue, while requiring replication and further validation before clinical translation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Where does histotripsy fit into hepatocellular carcinoma care?","authors":"Kelsey S. Lau-Min MD, MSCE,&nbsp;Jiping Wang MD, PhD","doi":"10.1002/cncr.70547","DOIUrl":"10.1002/cncr.70547","url":null,"abstract":"<div>\u0000 \u0000 <p>Histotripsy is a novel ultrasound-guided ablation technique that has been approved by the US Food and Drug Administration as a medical device for the noninvasive destruction of liver tumors. The noninvasive, nonthermal, nonionizing mechanical mechanism by which it destroys tumor tissues makes it an appealing local therapy option in the treatment of patients with early-stage hepatocellular carcinoma (HCC). In this article, the authors review the current evidence base for histotripsy in HCC and explore its potential role in routine care based on technical, safety, and clinical considerations. They then describe the evidence gaps that remain with respect to histotripsy’s treatment efficacy, comparative effectiveness, and safety relative to established local therapy options including thermal ablation, transarterial chemoembolization and radioembolization, and stereotactic body radiotherapy. Although the current body of evidence supports the technical feasibility, short-term safety, and early local tumor control of histotripsy in the treatment of patients with HCC, standardized response assessments, rigorous prospective evaluations of durable oncologic outcomes, and direct comparisons with existing therapies in well-defined patient populations are still needed before histotripsy can be fully integrated into standard HCC care.</p>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Not all methods for identifying high-risk smoldering myeloma measure up","authors":"Leah Lawrence","doi":"10.1002/cncr.70490","DOIUrl":"10.1002/cncr.70490","url":null,"abstract":"&lt;p&gt;In comparison with the 2/20/20 model, use of the AQUILA criteria resulted in a 3-fold greater number of patients with smoldering multiple myeloma (SMM) who were classified as high risk by capturing a group of patients with a lower risk of progression to multiple myeloma according to a retrospective study published in &lt;i&gt;JAMA Oncology&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In 2025, the US Food and Drug Administration (FDA) approved the first treatment for SMM—anti-CD38 monoclonal antibody daratumumab and hyaluronidase-fihj—for patients with high-risk disease.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In its approval of daratumumab, the FDA did not define “high-risk” but rather mentioned that 41% of patients had two or more of the criteria defined in the 2/20/20 model for high-risk SMM.&lt;/p&gt;&lt;p&gt;The approval was based on the results of the phase 3 AQUILA trial, which defined high-risk SMM by the presence of immunoparesis, a monoclonal protein (M-protein) level greater than 3.0 g/dL, an immunoglobin A isotype, a bone marrow plasma cell infiltration greater than 50%, or a free light chain ratio of 8 or greater.&lt;/p&gt;&lt;p&gt;However, in the time since the AQUILA trial was initiated, methods for defining SMM have evolved to more commonly use the 2/20/20 model, in which high-risk SMM is defined as the presence of more than one of three risk factors: an M-protein level greater than 2.0 g/dL, a bone marrow plasma cell infiltration greater than 20%, or a free light chain ratio greater than 20.&lt;/p&gt;&lt;p&gt;In this retrospective study, Cecilie V. Maeng, MD, a clinical researcher at Copenhagen University Hospital in Denmark, and her colleagues compared the AQUILA and 2/20/20 definitions of high-risk SMM.&lt;/p&gt;&lt;p&gt;In a screening cohort, 34% of participants had high-risk SMM according to AQUILA data versus 8% of participants with the 2/20/20 model. In a clinical cohort, 55% of patients met the high-risk criteria with AQUILA versus 19% of patients with the 2/20/20 model. The 2-year progression risk was 27.0% with the AQUILA definition and 44.1% with the 2/20/20 model.&lt;/p&gt;&lt;p&gt;Commenting on the analysis, Ajay K. Nooka, MD, MPH, a professor at Emory University School of Medicine in Atlanta, Georgia, explains that the results are a criticism of the AQUILA model.&lt;/p&gt;&lt;p&gt;“When they looked at these different criteria for high-risk SMM, the AQUILA model included more patients as high risk who, in fact, may not be high risk,” Dr Nooka says. However, he adds that the 2/20/20 model is also not an optimal model for defining high risk because it is a static model.&lt;/p&gt;&lt;p&gt;“The 2/20/20 model does not include an evolving serum M-protein,” Dr Nooka says. Studies have shown that defining risk with the inclusion of an evolving pattern versus a nonevolving one has a higher positive predictive value for high-risk SMM.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;“The gold standard for identifying high-risk SMM is the use of gene signatures that clearly differentiate between those that behave like multiple myeloma and those that behave","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New data inform decision-making for breast cancer surgeries","authors":"Leah Lawrence","doi":"10.1002/cncr.70488","DOIUrl":"10.1002/cncr.70488","url":null,"abstract":"&lt;p&gt;Patients diagnosed with breast cancer often have options when it comes to determining the best surgical management of their disease, with the potential risks and benefits of each approach discussed during shared decision-making conversations.&lt;/p&gt;&lt;p&gt;Two studies presented at the American Society of Breast Surgeons Annual Meeting compared outcomes related to different surgical approaches and provided patients and clinicians with more data to inform these decisions.&lt;/p&gt;&lt;p&gt;In the first study, researcher Jennifer Tseng, MD, an associate clinical professor and the medical director of breast surgery at the City of Hope Orange County in California, and her colleagues evaluated the trends and outcomes in the surgical management of women aged 45 years or younger with locoregionally advanced, high-risk breast cancer from the I-SPY2 clinical trial.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The study included 1737 patients, 40.2% of whom were aged 45 years or younger. Breast-conserving surgery (BCS) was performed less frequently in this younger group than in patients older than 45 years (36.8% vs. 48.5%; &lt;i&gt;p&lt;/i&gt; &lt; .001).&lt;/p&gt;&lt;p&gt;The analysis found that the extent of breast surgery—BCS versus mastectomy—was not associated with differences in overall survival or locoregional recurrence among women aged 45 years or younger with locoregionally advanced, high-risk breast cancer.&lt;/p&gt;&lt;p&gt;“Young women come to see me and automatically think they need a bilateral mastectomy to do better from a surgical perspective and a cancer control perspective,” Dr Tseng says. “These data highlight that the extent of surgery is important as far as making sure you get all the cancer out after systemic therapy, but removing the entire breast is not necessarily more helpful.”&lt;/p&gt;&lt;p&gt;Commenting on these results, Clara R. Farley, MD, FACS, an assistant professor in the Breast Surgical Oncology Division within the Winship Cancer Institute of Emory University in Atlanta, Georgia, says that the results shed light on overall risk and will help clinicians to better counsel patients.&lt;/p&gt;&lt;p&gt;“Work like this is helpful to inform shared decision-making conversations, particularly in young women who often feel that being more aggressive means better outcomes,” Dr Farley says. Instead of focusing on oncologic outcomes, these conversations can instead focus on other factors that may be important to the patient.&lt;/p&gt;&lt;p&gt;“Once a woman understands she can be safely managed with a mastectomy or breast conservation, we can then better discuss how those options may differ from a radiation, surgical recovery, cosmetic, and/or surveillance perspective. This ultimately helps guide our patients towards the right option for them.”&lt;/p&gt;&lt;p&gt;Katherine Kopkash, MD, the director of oncoplastic breast surgery at Endeavor Health and a clinical professor of surgery at the University of Chicago Pritzker School of Medicine in Illinois, and her colleagues presented data comparing nipple-sparing mastectomies performed with open surgery","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2-targeting zongertinib shows early activity in untreated advanced HER2-mutant NSCLC","authors":"Leah Lawrence","doi":"10.1002/cncr.70489","DOIUrl":"10.1002/cncr.70489","url":null,"abstract":"&lt;p&gt;The &lt;i&gt;HER2&lt;/i&gt;-targeting tyrosine kinase inhibitor (TKI) zongertinib showed benefit in patients with advanced &lt;i&gt;HER2&lt;/i&gt;-mutant non–small cell lung cancer (NSCLC) according to data from cohort 2 of the Beamion LUNG-1 trial published in &lt;i&gt;The New England Journal of Medicine&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Zongertinib received accelerated approval for adults with unresectable or metastatic NSCLC who have previously received systemic therapy based on results from cohort 1 of the Beamion LUNG-1 trial.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Cohort 2 included 74 patients with previously untreated advanced or metastatic nonsquamous &lt;i&gt;HER2&lt;/i&gt;-mutant NSCLC who received 120 mg of zongertinib once daily. The primary endpoint was objective response by independent central review.&lt;/p&gt;&lt;p&gt;As of August 2025, 76% of patients who received 120 mg of zongertinib had a confirmed objective response, with 11% of patients achieving a complete response. The median duration of response was 15.2 months. Median progression-free survival was 14.4 months.&lt;/p&gt;&lt;p&gt;Adverse events of any grade occurred in 99% of patients, with grade 3 or higher events reported in 45% of patients. The most common grade 3 or higher adverse events were increased alanine aminotransferase levels and decreased ejection fraction.&lt;/p&gt;&lt;p&gt;Treatment-related adverse events (TRAEs) occurred in 91% of patients, with grade 3 or higher TRAEs occurring in 19% of patients. There were two cases of interstitial lung disease or pneumonitis, both considered treatment-related.&lt;/p&gt;&lt;p&gt;Published data also included outcomes from an exploratory cohort 4, which evaluated 30 patients with active brain metastases. Here, the confirmed intracranial objective response rate was 47%, with TRAEs occurring in 17% of patients.&lt;/p&gt;&lt;p&gt;Daniel Morgensztern, MD, a professor of medicine at the Washington University School of Medicine in St. Louis, Missouri, described the results as remarkable.&lt;/p&gt;&lt;p&gt;“The objective response of 76% and median progression-free survival of 14.4 months achieved with zongertinib compares favorably with trastuzumab deruxtecan, adding the convenience of oral administration,” Dr Morgensztern says.&lt;/p&gt;&lt;p&gt;The antibody–drug conjugate trastuzumab deruxtecan, which is given as an intravenous infusion, was the first &lt;i&gt;HER2&lt;/i&gt;-directed therapy approved by the US Food and Drug Administration in 2022 for patients with previously treated metastatic &lt;i&gt;HER2&lt;/i&gt;-mutant NSCLC.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; In late 2025, another &lt;i&gt;HER2&lt;/i&gt;-targeting TKI, sevabertinib, was approved for patients with locally advanced or metastatic &lt;i&gt;HER2&lt;/i&gt;-mutant NSCLC who have received prior systemic therapy.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;“Because [&lt;i&gt;HER2&lt;/i&gt;] is an uncommon mutation in NSCLC, the 74 patients enrolled into cohort 2 of this phase 1 trial was sufficient to establish the role for zongertinib in the first-line setting,” Dr Morgensztern says. “The preferred treatment for patients with &lt;i&gt;HER2&lt;/i&gt;-mutant NSCLC should be with a TKI.","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"36 is the new 18: Functional high-risk multiple myeloma in the modern era","authors":"Swetha Reddi MD,&nbsp;Rahul Banerjee MD","doi":"10.1002/cncr.70548","DOIUrl":"10.1002/cncr.70548","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vobramitamab duocarmazine, an anti–B7-H3 antibody–drug conjugate, in patients with advanced solid tumors: Final results of a phase 1 cohort expansion","authors":"Eugene Shenderov MD, PhD,&nbsp;Manish R. Sharma MD,&nbsp;Elena Garralda MD,&nbsp;John Powderly MD,&nbsp;Iwona Ługowska MD,&nbsp;Alexander Spira MD, PhD,&nbsp;Marc Cucurull Salamero MD,&nbsp;Sekwon Jang MD,&nbsp;Rasha Cosman BMedSc, MBBS, FRACP,&nbsp;John Shen MD,&nbsp;Wen Xu BMedSc, MBBS, FRACP,&nbsp;Piotr J. Wysocki MD, PhD,&nbsp;Rodryg Ramlau MD, PhD,&nbsp;Emmanuel S. Antonarakis MD,&nbsp;Andrew J. Weickhardt MBBS, FRACP, DMedSc,&nbsp;Jakub Żołnierek MD, PhD,&nbsp;Emiliano Calvo MD, PhD,&nbsp;Enxu Zhao MS,&nbsp;Chet Bohac MD,&nbsp;Ashley Ward MD,&nbsp;Girish Mallesara MBBS, MD, DM, FRACP","doi":"10.1002/cncr.70544","DOIUrl":"10.1002/cncr.70544","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Vobramitamab duocarmazine is an investigational antibody–drug conjugate (ADC) targeting B7 homolog 3 (B7-H3) with a cytotoxic duocarmycin-based DNA-alkylating payload. This study evaluated its safety and antitumor activity in advanced solid tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this phase 1/2 trial (CP-MGC-018-01/NCT03729596), vobramitamab duocarmazine was evaluated at 0.5–4.0 mg/kg intravenously every 3 weeks. The multicohort tumor-expansion phase focused on metastatic castration-resistant prostate cancer (mCRPC), lung, breast, melanoma, and squamous head and neck carcinomas. Primary end points were safety and tolerability. Secondary end points included pharmacokinetics, immunogenicity, and antitumor activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across vobramitamab duocarmazine–treated patients, 97.9% (140 of 143) experienced treatment-related adverse events (TRAEs) of all grades; the grade ≥3 TRAE rate was 65.0% (93 of 143). With two dose-limiting toxicities in patients receiving 4.0 mg/kg (grade 4 afebrile neutropenia and grade 3 fatigue), the recommended dose for expansion was 3.0 mg/kg. Among all patients treated at 3.0 mg/kg, the rate of grade ≥3 TRAEs was 65.3% (79 of 121) and the confirmed objective response rate (ORR) was 7.2% (seven of 97), with a 6.3-month median duration of response (DOR). Among patients with mCRPC receiving 3.0 mg/kg, the confirmed ORR was 8.3% (two of 24), with a 5.3-month median DOR; the confirmed prostate-specific antigen with a ≥50% decline from the baseline response rate was 43.9% (18 of 41), with a 6.2-month median DOR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Vobramitamab duocarmazine demonstrated modest antitumor activity across tumor types, with the most pronounced activity in mCRPC. Treatment was limited by toxicity, particularly pleural effusions and fatigue, which restricted dosing duration. Study treatment was discontinued to refocus on mCRPC in a randomized phase 2 study (TAMARACK/NCT05551117), which was later discontinued after assessment of the vobramitamab duocarmazine safety and efficacy profile.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 15","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}