{"title":"Pediatric-Friendly Formulations: Critical to Maximizing Benefit of Novel Therapeutics Such as Selumetinib for Children With Neurofibromatosis and Other Neoplasms.","authors":"Brooke Bernhardt,Brenda J Weigel","doi":"10.1200/jco-25-02765","DOIUrl":"https://doi.org/10.1200/jco-25-02765","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"87 1","pages":"JCO2502765"},"PeriodicalIF":45.3,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056773","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}
Bradley J Stish, Gina L Mazza, Jones T Nauseef, Michael Sandon Humeniuk, Thomas J Smith, Cindy Tofthagen, Dayssy Alexandra Diaz Pardo, Christopher Chay, Andrew J Huang, Kushal Naha, Scott T Tagawa, Selina Chow, Kathryn J Ruddy, Maryam B Lustberg, Lucile L Adams-Campbell, Paul J Novotny, Charles L Loprinzi
Purpose: Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer.
Patients and methods: Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline at 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash-Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms.
Results: Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 (P = .02), and 6.89 (P < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 (P = .07), and 13.95 (P = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg (P = .042) and 5 mg (P < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo.
Conclusion: Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.
{"title":"Alliance A222001: Oxybutynin Versus Placebo for the Treatment of Hot Flashes in Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer.","authors":"Bradley J Stish, Gina L Mazza, Jones T Nauseef, Michael Sandon Humeniuk, Thomas J Smith, Cindy Tofthagen, Dayssy Alexandra Diaz Pardo, Christopher Chay, Andrew J Huang, Kushal Naha, Scott T Tagawa, Selina Chow, Kathryn J Ruddy, Maryam B Lustberg, Lucile L Adams-Campbell, Paul J Novotny, Charles L Loprinzi","doi":"10.1200/JCO-25-01486","DOIUrl":"10.1200/JCO-25-01486","url":null,"abstract":"<p><strong>Purpose: </strong>Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer.</p><p><strong>Patients and methods: </strong>Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline at 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash-Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms.</p><p><strong>Results: </strong>Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 (<i>P</i> = .02), and 6.89 (<i>P</i> < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 (<i>P</i> = .07), and 13.95 (<i>P</i> = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg (<i>P</i> = .042) and 5 mg (<i>P</i> < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo.</p><p><strong>Conclusion: </strong>Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501486"},"PeriodicalIF":41.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12871868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052342","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}
PURPOSEThe incidence of young-onset pancreatic cancer has increased rapidly; however, the dose-response relationship between alcohol consumption and the risk of incident young-onset pancreatic cancer remains unclear.METHODSA nationwide cohort of 6,263,770 individuals age 20 to 39 years who underwent national health screening in Korea between 2009 and 2012 was followed until December 2020. Heavy alcohol consumption was defined as ≥30 g/day for men and ≥16 g/day for women. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs.RESULTSA total of 1,515 cases of young-onset pancreatic cancer were identified. The cumulative incidence was consistently higher among heavy drinkers compared with nondrinkers or light-to-moderate drinkers (log-rank P < .001). Heavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer (aHR, 1.19 [95% CI, 1.004 to 1.42]), whereas light-to-moderate consumption was not (aHR, 1.04 [95% CI, 0.92 to 1.17]). In addition, alcohol consumption ≥3 times per week was associated with an increased risk (aHR, 1.23 [95% CI, 1.01 to 1.51]). No significant interactions were observed across most subgroups, including age, sex, obesity, smoking status, diabetes, and pancreatitis (all P for interaction > .05), except for physical activity (P = .011).CONCLUSIONHeavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer in a threshold dose-response manner. These findings suggest that early public health strategies to reduce heavy alcohol consumption among young adults may help mitigate the growing burden of young-onset pancreatic cancer.
{"title":"Threshold Dose-Response Association Between Alcohol Consumption and Risk of Young-Onset Pancreatic Cancer: A Nationwide Korean Cohort Study of Young Adults Age 20-39 Years.","authors":"Joo-Hyun Park,Jung Yong Hong,Kyungdo Han,Jay J Shen,Joon Oh Park,Young Suk Park,Ho Yeong Lim","doi":"10.1200/jco-25-01169","DOIUrl":"https://doi.org/10.1200/jco-25-01169","url":null,"abstract":"PURPOSEThe incidence of young-onset pancreatic cancer has increased rapidly; however, the dose-response relationship between alcohol consumption and the risk of incident young-onset pancreatic cancer remains unclear.METHODSA nationwide cohort of 6,263,770 individuals age 20 to 39 years who underwent national health screening in Korea between 2009 and 2012 was followed until December 2020. Heavy alcohol consumption was defined as ≥30 g/day for men and ≥16 g/day for women. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs.RESULTSA total of 1,515 cases of young-onset pancreatic cancer were identified. The cumulative incidence was consistently higher among heavy drinkers compared with nondrinkers or light-to-moderate drinkers (log-rank P < .001). Heavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer (aHR, 1.19 [95% CI, 1.004 to 1.42]), whereas light-to-moderate consumption was not (aHR, 1.04 [95% CI, 0.92 to 1.17]). In addition, alcohol consumption ≥3 times per week was associated with an increased risk (aHR, 1.23 [95% CI, 1.01 to 1.51]). No significant interactions were observed across most subgroups, including age, sex, obesity, smoking status, diabetes, and pancreatitis (all P for interaction > .05), except for physical activity (P = .011).CONCLUSIONHeavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer in a threshold dose-response manner. These findings suggest that early public health strategies to reduce heavy alcohol consumption among young adults may help mitigate the growing burden of young-onset pancreatic cancer.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"21 1","pages":"JCO2501169"},"PeriodicalIF":45.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033571","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}
PURPOSEThe neoCARHP aimed to investigate the efficacy and safety of investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) plus trastuzumab and pertuzumab, with carboplatin (TCbHP) or without carboplatin (THP), in stage II and III human epidermal growth factor receptor 2 (HER2)-positive breast cancer.METHODSThe neoCARHP was a multicenter, randomized, phase III, noninferiority study. Eligible patients were women age 18 years or older with previously untreated, stage II and III, HER2-positive invasive breast cancer. Patients were randomly assigned (1:1) to receive six 3-week cycles of TCbHP or THP. The primary end point was pathologic complete response (pCR) rate in the breast and axilla (ypT0/is ypN0) in the modified intention-to-treat (mITT) population (all randomly assigned patients receiving at least one dose of study treatment). Safety was evaluated in all patients who received any study treatment.RESULTSBetween April 30, 2021, and August 27, 2024, 774 patients were randomly assigned and 766 were included in the mITT population (382 in THP and 384 in TCbHP). pCR was achieved in 245 (64.1% [95% CI, 59.1 to 69.0]) patients in the THP group and 253 (65.9% [60.9-70.6]) in the TCbHP group (absolute difference, -1.8% [95% CI, -8.5 to 5.0]; odds ratio, 0.93 [95% CI, 0.69 to 1.25]; Pnoninferiority = .0089). The THP group had fewer grade 3 and 4 adverse events (20.7% v 34.6%) and serious adverse events (1.3% v 4.7%) than the TCbHP group. The most common grade 3 and 4 adverse events with THP were neutropenia (6.8% v 16.4% with TCbHP), leukopenia (5.5% v 14.8%), and diarrhea (2.6% v 4.2%). No treatment-associated deaths occurred.CONCLUSIONTHP provided noninferior pCR rates and improved tolerability compared with TCbHP. Omitting carboplatin may be applicable in HER2-positive breast cancer.
neoCARHP旨在研究研究者选择的紫杉醇（多西紫杉醇、紫杉醇或nab-紫杉醇）联合曲妥珠单抗和帕妥珠单抗，联合卡铂（TCbHP）或不联合卡铂（THP）治疗II期和III期人表皮生长因子受体2 （HER2）阳性乳腺癌的疗效和安全性。方法neoCARHP是一项多中心、随机、III期、非劣效性研究。符合条件的患者是年龄在18岁或以上的未接受治疗的II期和III期her2阳性浸润性乳腺癌女性。患者被随机分配（1:1）接受6个3周周期的TCbHP或THP治疗。主要终点是修改意向治疗（mITT）人群中乳腺和腋窝的病理完全缓解（pCR）率（ypT0/is ypN0）（所有随机分配的患者接受至少一个剂量的研究治疗）。对所有接受任何研究治疗的患者进行安全性评估。结果在2021年4月30日至2024年8月27日期间，774名患者被随机分配，766名患者被纳入mITT人群（382名THP患者和384名TCbHP患者）。在245例THP组（64.1% [95% CI, 59.1 ~ 69.0]）和253例TCbHP组（65.9%[60.9 ~ 70.6]）患者中进行了pCR检测（绝对差异为-1.8% [95% CI, -8.5 ~ 5.0]；优势比为0.93 [95% CI, 0.69 ~ 1.25]；非劣效性= 0.0089）。与TCbHP组相比，THP组3级和4级不良事件（20.7% vs 34.6%）和严重不良事件（1.3% vs 4.7%）较少。THP最常见的3级和4级不良事件是中性粒细胞减少（6.8% vs 16.4% TCbHP），白细胞减少（5.5% vs 14.8%）和腹泻（2.6% vs 4.2%）。无治疗相关死亡发生。结论与TCbHP相比，thp具有良好的pCR率和耐受性。省略卡铂可能适用于her2阳性乳腺癌。
{"title":"Neoadjuvant Taxane Plus Trastuzumab and Pertuzumab With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: The Randomized Noninferiority Phase III neoCARHP Trial.","authors":"Hong-Fei Gao,Guo-Lin Ye,Ying Lin,Qin Huang,Jie Dong,Yin Cao,Yan-Xia Zhao,Qian-Jun Chen,Shi-Hui Ma,Jie Ouyang,Jin-Hui Ye,Hua-Wei Yang,Yuan-Qi Zhang,Yong-Cheng Zhang,Gang-Ling Zhang,Wei Li,Yunjian Zhang,Zhi-Yong Wu,Ying-Yi Lin,Teng Zhu,Liu-Lu Zhang,Ci-Qiu Yang,Mei Yang,Hao Peng,Bo Chen,Yi-Tian Chen,Fei Ji,Min-Yi Cheng,Jie-Qing Li,Zefei Jiang,Kun Wang","doi":"10.1200/jco-25-02176","DOIUrl":"https://doi.org/10.1200/jco-25-02176","url":null,"abstract":"PURPOSEThe neoCARHP aimed to investigate the efficacy and safety of investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) plus trastuzumab and pertuzumab, with carboplatin (TCbHP) or without carboplatin (THP), in stage II and III human epidermal growth factor receptor 2 (HER2)-positive breast cancer.METHODSThe neoCARHP was a multicenter, randomized, phase III, noninferiority study. Eligible patients were women age 18 years or older with previously untreated, stage II and III, HER2-positive invasive breast cancer. Patients were randomly assigned (1:1) to receive six 3-week cycles of TCbHP or THP. The primary end point was pathologic complete response (pCR) rate in the breast and axilla (ypT0/is ypN0) in the modified intention-to-treat (mITT) population (all randomly assigned patients receiving at least one dose of study treatment). Safety was evaluated in all patients who received any study treatment.RESULTSBetween April 30, 2021, and August 27, 2024, 774 patients were randomly assigned and 766 were included in the mITT population (382 in THP and 384 in TCbHP). pCR was achieved in 245 (64.1% [95% CI, 59.1 to 69.0]) patients in the THP group and 253 (65.9% [60.9-70.6]) in the TCbHP group (absolute difference, -1.8% [95% CI, -8.5 to 5.0]; odds ratio, 0.93 [95% CI, 0.69 to 1.25]; Pnoninferiority = .0089). The THP group had fewer grade 3 and 4 adverse events (20.7% v 34.6%) and serious adverse events (1.3% v 4.7%) than the TCbHP group. The most common grade 3 and 4 adverse events with THP were neutropenia (6.8% v 16.4% with TCbHP), leukopenia (5.5% v 14.8%), and diarrhea (2.6% v 4.2%). No treatment-associated deaths occurred.CONCLUSIONTHP provided noninferior pCR rates and improved tolerability compared with TCbHP. Omitting carboplatin may be applicable in HER2-positive breast cancer.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"32 1","pages":"JCO2502176"},"PeriodicalIF":45.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033568","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}
Emily Alger,Olalekan Lee Aiyegbusi,Amylou C Dueck,Anna Minchom,Madeline Pe,John D Peipert,Claire Snyder,Stefan N Symeonides,Roger Wilson,Ethan Basch,Yu Qiao,Susan E Bates,Helen Bulbeck,Lizzie Dean,Massimo Di Maio,Aaron R Hansen,Olga Kholmanskikh,Ken Kobayashi,Dónal Landers,Christophe Le Tourneau,J Jack Lee,Brigette B Y Ma,Lynley V Marshall,Sheetal Patel,Joan Petrie,Gregory R Pond,Kieran Prior,Khadija R Rantell,John F Reeve,Olga Solovyeva,Nolan A Wages,Harald A Weber,Melanie J Calvert,Christina Yap
PURPOSEThere is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs.METHODSUsing the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion.RESULTSConsensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies.CONCLUSIONThis foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation-ultimately contributing to the development of safer, more effective therapies.
{"title":"International Consensus-Driven Recommendations for Patient-Reported Outcome Research Objectives in Early Phase Dose-Finding Oncology Trials: OPTIMISE-ROR.","authors":"Emily Alger,Olalekan Lee Aiyegbusi,Amylou C Dueck,Anna Minchom,Madeline Pe,John D Peipert,Claire Snyder,Stefan N Symeonides,Roger Wilson,Ethan Basch,Yu Qiao,Susan E Bates,Helen Bulbeck,Lizzie Dean,Massimo Di Maio,Aaron R Hansen,Olga Kholmanskikh,Ken Kobayashi,Dónal Landers,Christophe Le Tourneau,J Jack Lee,Brigette B Y Ma,Lynley V Marshall,Sheetal Patel,Joan Petrie,Gregory R Pond,Kieran Prior,Khadija R Rantell,John F Reeve,Olga Solovyeva,Nolan A Wages,Harald A Weber,Melanie J Calvert,Christina Yap","doi":"10.1200/jco-25-01625","DOIUrl":"https://doi.org/10.1200/jco-25-01625","url":null,"abstract":"PURPOSEThere is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs.METHODSUsing the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion.RESULTSConsensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies.CONCLUSIONThis foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation-ultimately contributing to the development of safer, more effective therapies.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"17 1","pages":"JCO2501625"},"PeriodicalIF":45.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rise and Fall of Neoadjuvant Carboplatin for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.","authors":"Paolo Tarantino","doi":"10.1200/jco-25-02855","DOIUrl":"https://doi.org/10.1200/jco-25-02855","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"39 1","pages":"JCO2502855"},"PeriodicalIF":45.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Windows of Opportunity in Breast Cancer: Learning More From Fewer Patients in a Shorter Time.","authors":"Susan G Hilsenbeck,Alastair M Thompson","doi":"10.1200/jco-25-02714","DOIUrl":"https://doi.org/10.1200/jco-25-02714","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"75 1","pages":"JCO2502714"},"PeriodicalIF":45.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BR.31 Trial: Adjuvant Durvalumab as the Third Contender in Resected Non-Small Cell Lung Cancer.","authors":"Jordi Remon,Tina Cascone,Solange Peters","doi":"10.1200/jco-25-02696","DOIUrl":"https://doi.org/10.1200/jco-25-02696","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"8 1","pages":"JCO2502696"},"PeriodicalIF":45.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021565","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}
Martin Wermke,Valentina Gambardella,Yasutoshi Kuboki,Enriqueta Felip,Miguel F Sanmamed,Olatunji B Alese,Cyrus M Sayehli,Edurne Arriola,Jürgen Wolf,Liza C Villaruz,Julia Bertulis,Matus Studeny,Mohamed Bouzaggou,Xiaoyan Fang,Daniel Morgensztern
{"title":"Reply to: Delta-Like Ligand 3 Expression Across Lung Neuroendocrine Subtypes: Interpreting Response in Small Cell Lung Cancer and Beyond.","authors":"Martin Wermke,Valentina Gambardella,Yasutoshi Kuboki,Enriqueta Felip,Miguel F Sanmamed,Olatunji B Alese,Cyrus M Sayehli,Edurne Arriola,Jürgen Wolf,Liza C Villaruz,Julia Bertulis,Matus Studeny,Mohamed Bouzaggou,Xiaoyan Fang,Daniel Morgensztern","doi":"10.1200/jco-25-02654","DOIUrl":"https://doi.org/10.1200/jco-25-02654","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"69 1","pages":"JCO2502654"},"PeriodicalIF":45.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021567","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}
PURPOSEPatients with human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) and advanced stage and/or significant smoking history are at higher risk of relapse. Induction immunotherapy before chemoradiation (CRT) may improve outcomes. This randomized phase II trial assessed the feasibility and safety of induction nivolumab before CRT in this high-risk population.METHODSEligible patients had HPV-positive OPC with either T4 and/or N2/N3 disease or a smoking history >10 pack-years. Patients were randomly assigned 1:2 to receive either standard CRT (70 Gy with cisplatin, control arm [CA], n = 20) or two infusions of nivolumab followed by CRT (experimental arm [EA], n = 41). The primary end point was the rate of patients who received full treatment in due time (FTDT), defined as (1) two nivolumab infusions on days 1 and 13-17, (2) CRT started between days 27-37 after the first nivolumab infusion, (3) no radiotherapy break ≥7 days, (4) >95% of theoretical/prescribed RT dose, and (5) cisplatin dose received ≥200 mg/m2. If two patients or less in the EA failed FTDT, the strategy would be considered feasible. Secondary end points included oncologic outcomes and toxicity.RESULTSBetween July 2019 and September 2021, 62 patients were randomly assigned. Median follow-up was 37.5 months. The primary end point was not met: four of 41 patients in EA received <200 mg/m2 cisplatin. Grade 4 to 5 acute adverse events occurred only in EA, in seven patients. The 2-year cumulative incidence (95% CI) of relapse was 7.3% (1.9 to 18.0) in EA versus 15.0% (3.6 to 34.0) in CA.CONCLUSIONInduction nivolumab before CRT did not meet the predefined feasibility threshold because of reduced cisplatin dosing after toxicity in 10% of patients. The relapse incidence was numerically lower in the EA but this finding is exploratory and requires confirmation.
目的人乳头瘤病毒（HPV）阳性口咽癌（OPC）晚期和/或有明显吸烟史的患者复发风险较高。放化疗前诱导免疫治疗（CRT）可能改善预后。这项随机II期试验评估了高危人群在CRT前使用诱导纳武单抗的可行性和安全性。方法hpv阳性OPC患者合并T4和/或N2/N3疾病或吸烟史≥10包年。患者按1:2随机分配，接受标准CRT （70 Gy顺铂，对照组[CA]， n = 20）或两次输注纳沃单抗后再接受CRT（实验组[EA]， n = 41）。主要终点是按时接受充分治疗的患者比率（FTDT），定义为(1)第1天和第13-17天两次纳武单抗输注，(2)第一次纳武单抗输注后27-37天开始CRT，(3)放疗无中断≥7天，(4)理论/处方RT剂量的95%，(5)顺铂剂量≥200mg /m2。如果EA中有两个或更少的患者FTDT失败，则认为该策略是可行的。次要终点包括肿瘤预后和毒性。结果在2019年7月至2021年9月期间，随机分配了62例患者。中位随访时间为37.5个月。主要终点未达到：41例EA患者中有4例接受了< 200mg /m2的顺铂治疗。4 - 5级急性不良事件仅发生在EA患者中，7例。EA组的2年累积复发发生率（95% CI）为7.3%(1.9 ~ 18.0)，而ca组为15.0%（3.6 ~ 34.0）。结论在CRT前诱导纳沃单抗未达到预先设定的可行性阈值，因为10%的患者毒性后顺铂剂量减少。EA的复发率在数字上较低，但这一发现是探索性的，需要证实。
{"title":"Induction Nivolumab Before Chemoradiation in High-Risk Human Papillomavirus-Driven Oropharynx Cancers: IMMUNEBOOST-HPV, a Multicenter Randomized Phase II Trial.","authors":"Haitham Mirghani,Anne Aupérin,Caroline Even,Alicia Larive,Jerome Fayette,Lionnel Geoffrois,Florian Clatot,Benoit Calderon,Yungan Tao,France Nguyen,Emmanuelle Fabiano,Sarah Kreps,Anne-Laure Gaultier,Francois Bidault,Julien Puech,Benjamin Morin,Lea Picavet,Eric Tartour,Aicha Ben Hariz,Michael Chevrot,Laure Monard,David Veyer,Cecile Badoual,Helene Péré,Pierre Blanchard","doi":"10.1200/jco-25-00835","DOIUrl":"https://doi.org/10.1200/jco-25-00835","url":null,"abstract":"PURPOSEPatients with human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) and advanced stage and/or significant smoking history are at higher risk of relapse. Induction immunotherapy before chemoradiation (CRT) may improve outcomes. This randomized phase II trial assessed the feasibility and safety of induction nivolumab before CRT in this high-risk population.METHODSEligible patients had HPV-positive OPC with either T4 and/or N2/N3 disease or a smoking history >10 pack-years. Patients were randomly assigned 1:2 to receive either standard CRT (70 Gy with cisplatin, control arm [CA], n = 20) or two infusions of nivolumab followed by CRT (experimental arm [EA], n = 41). The primary end point was the rate of patients who received full treatment in due time (FTDT), defined as (1) two nivolumab infusions on days 1 and 13-17, (2) CRT started between days 27-37 after the first nivolumab infusion, (3) no radiotherapy break ≥7 days, (4) >95% of theoretical/prescribed RT dose, and (5) cisplatin dose received ≥200 mg/m2. If two patients or less in the EA failed FTDT, the strategy would be considered feasible. Secondary end points included oncologic outcomes and toxicity.RESULTSBetween July 2019 and September 2021, 62 patients were randomly assigned. Median follow-up was 37.5 months. The primary end point was not met: four of 41 patients in EA received <200 mg/m2 cisplatin. Grade 4 to 5 acute adverse events occurred only in EA, in seven patients. The 2-year cumulative incidence (95% CI) of relapse was 7.3% (1.9 to 18.0) in EA versus 15.0% (3.6 to 34.0) in CA.CONCLUSIONInduction nivolumab before CRT did not meet the predefined feasibility threshold because of reduced cisplatin dosing after toxicity in 10% of patients. The relapse incidence was numerically lower in the EA but this finding is exploratory and requires confirmation.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"57 1","pages":"JCO2500835"},"PeriodicalIF":45.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021564","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}
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