Journal of Clinical Oncology最新文献

{"title":"Total Neoadjuvant Therapy With Long-Course Radiotherapy Versus Chemoradiotherapy in High-Risk Locally Advanced Rectal Cancer (TNTCRT): A Multicenter, Randomized, Phase III Trial.","authors":"Xin Wang, Yuanling Tang, Junyang Lu, Wenjian Meng, Ping Liu, Jitao Zhou, Feng Wen, Peirong Ding, Jun Li, Biao Wang, Qing Guo, Jian Qiu, Hao Sun, Xiangbing Deng, Yali Shen, Hanjiang Zeng, Dan Jiang, Di Wang, Yunfeng Li, Yi Xiao, Ziqiang Wang","doi":"10.1200/JCO-25-03110","DOIUrl":"10.1200/JCO-25-03110","url":null,"abstract":"<p><strong>Purpose: </strong>High-risk locally advanced rectal cancer (LARC) carries a substantial risk of distant recurrence, which limits disease-free survival (DFS). We compared total neoadjuvant therapy (TNT) integrating long-course radiotherapy (LCRT) with uninterrupted doublet chemotherapy (doublet-LC TNT) versus conventional neoadjuvant chemoradiotherapy (nCRT).</p><p><strong>Methods: </strong>In this multicenter, randomized, phase III trial, patients with stage II/III LARC and at least 1 high-risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion) were enrolled. Patients were assigned to doublet-LC TNT (induction, concurrent, and consolidation capecitabine plus oxaliplatin with LCRT) before surgery or nCRT (capecitabine with LCRT) followed by surgery and adjuvant chemotherapy. The primary end point was DFS (ClinicalTrials.gov identifier: NCT03177382).</p><p><strong>Results: </strong>Between June 6, 2017, and December 27, 2023, 458 patients were randomly assigned to doublet-LC TNT (n = 232) or nCRT (n = 226). At a median follow-up of 51 months, doublet-LC TNT improved 3-year DFS (74.8% <i>v</i> 66.0%; hazard ratio [HR], 0.674 [95% CI, 0.489 to 0.929]; <i>P</i> = .016). Metastasis-free survival (MFS; 77.7% <i>v</i> 67.6%; HR, 0.655 [95% CI, 0.469 to 0.915]) and pathologic complete response rates (pCR; 26.37% <i>v</i> 9.80%; <i>P</i> < .001) were higher with doublet-LC TNT, whereas locoregional failure remained low and comparable (6.03% <i>v</i> 6.19%; <i>P</i> = .943). Although grade ≥3 adverse events during the neoadjuvant phase were more frequent with doublet-LC TNT (27.59% <i>v</i> 8.56%; <i>P</i> < .001), severe toxicities during the entire treatment course (28.02% <i>v</i> 24.32%; <i>P</i> = .371) and major postoperative complications (3.98% <i>v</i> 2.94%; <i>P</i> = .567) were comparable.</p><p><strong>Conclusion: </strong>Compared with conventional nCRT, doublet-LC TNT improved DFS, MFS, and pCR rates with manageable toxicity. These findings support this intensified, doublet-based regimen as a standard option within the modern TNT paradigm. Further comparative studies are warranted to evaluate these results against other short-course radiotherapy‑based or nondoublet-concurrent TNT regimens.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2409-2421"},"PeriodicalIF":44.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578760","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":"Reduced/No Dexamethasone With Netupitant/Palonosetron and Olanzapine for Chemotherapy‑Induced Nausea/Vomiting in Highly Emetogenic Chemotherapy: Phase III Noninferiority Trial.","authors":"Yanchun Meng, Yingying Liu, Mingxi Lin, Lili Wang, Yuxin Mu, Ling Yang, Yiqun Du, Xiaojun Liu, Yong Chen, Shaodong Tian, Qin Zhou, Xiaojie Zhuang, Zikang Li, Jinsong Liu, Shencun Fang, Weifei Fan, Yu Mao, Ling Zhang, Hao Wu, Fei Yan, Jie Weng, Jianhua Zhao, Xiangyu Long, Lianfang Liu, Jianbo Zhou, Jian Zhang","doi":"10.1200/JCO-26-01029","DOIUrl":"10.1200/JCO-26-01029","url":null,"abstract":"<p><strong>Purpose: </strong>Guideline-recommended 4-day dexamethasone (DEX) for highly emetogenic chemotherapy (HEC) raises toxicity and immunotherapy interference concerns. We tested whether DEX reduction or omission with netupitant/palonosetron (NEPA) plus olanzapine (OLZ) is noninferior to standard DEX.</p><p><strong>Patients and methods: </strong>In this open-label, randomized phase III noninferiority trial across 28 Chinese centers, adults receiving HEC received NEPA (day 1) plus OLZ (days 1-4) and were randomly assigned to standard DEX (12 mg day 1, 8 mg days 2-4), DEX-sparing (6 mg day 1 only), or DEX-free (no DEX). The primary end point was complete response (CR; no emesis/no rescue medication) from 0 to 120 h. Noninferiority margin was -12% (one-sided α = .025).</p><p><strong>Results: </strong>Of 644 randomly assigned patients (median age 54.9 years; 66.0% female), stratified analysis showed overall CR rates of 72.4% for standard, 72.2% for DEX-sparing (stratified risk difference [RD], -0.2% [95% CI, -8.7 to 8.5]; <i>P</i>_{noninferiority} = .005), and 70.1% for DEX-free (stratified RD, -2.2% [95% CI, -10.7 to 6.4]; <i>P</i>_{noninferiority} = .014). Both met noninferiority, confirmed in per-protocol analysis. Steroid-related toxicities were significantly lower with DEX-sparing and DEX-free regimens versus standard.</p><p><strong>Conclusion: </strong>NEPA plus OLZ with reduced (6 mg day 1 only) or no DEX is noninferior to standard 4-day DEX for chemotherapy-induced nausea and vomiting prevention in HEC, supporting steroid-sparing strategies particularly relevant in the chemo-immunotherapy era.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2390-2399"},"PeriodicalIF":44.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163256","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":"Erratum: Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Myelofibrosis: Phase III SENTRY Trial.","authors":"Prithviraj Bose, Haris Ali, Haifa Kathrin Al-Ali, Valentin Garcia-Gutierrez, Sebastian Grosicki, Zhanet Grudeva-Popova, Claire Harrison, Junshik Hong, Hsin-An Hou, Michal Kwiatek, Michael Loschi, Francesco Passamonti, Nikolai Podoltsev, Raajit Rampal, Srinivas Tantravahi, Laura Gabriela Urian, Yi Chai, Pietro Taverna, Tomer Mark, Amama Sadiq, Reshma Rangwala, Pankit Vachhani, John Mascarenhas","doi":"10.1200/JCO-26-01827","DOIUrl":"10.1200/JCO-26-01827","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2465"},"PeriodicalIF":44.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630231","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":"Perioperative Durvalumab for Resectable Non-Small Cell Lung Cancer: Updated Outcomes From the Phase III AEGEAN Trial.","authors":"John V Heymach, Jie He, David Harpole, Tetsuya Mitsudomi, Janis M Taube, Shugeng Gao, Laszlo Urban, Jin Hyoung Kang, Francisco J Orlandi, Jeronimo Rodriguez-Cid, Bartomeu Massuti, Luis Leon Mateos, Giulia Pasello, Quincy Chu, Jaroslaw Kolb-Sielecki, Masao Nakata, Gabriella Galffy, Maximilian Hochmair, Thomas Winder, Ruslan Zukov, Gabriel Garbaos, Yoshitsugu Horio, Gyula Ostoros, Tho V Tran, Jian You, Kang-Yun Lee, Lorenzo Antonuzzo, Hiroaki Akamatsu, Bivas Biswas, Alexander Spira, Jeffrey Crawford, Ha T Le, Mike Aperghis, Helen Mann, Tamer M Fouad, Gary J Doherty, Martin Reck","doi":"10.1200/JCO-25-02659","DOIUrl":"https://doi.org/10.1200/JCO-25-02659","url":null,"abstract":"<p><p>In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (EFS) and pathologic complete response in patients with resectable non-small cell lung cancer (R-NSCLC), with a safety profile consistent with the individual agents. We report EFS from a second planned interim analysis, interim disease-free survival (DFS) and overall survival (OS), and safety, after all patients completed/discontinued treatment. In this phase III, double-blind, placebo-controlled study, patients with treatment-naïve R-NSCLC (stage II-IIIB [N2]) were randomly assigned (1:1) to neoadjuvant platinum-based chemotherapy plus durvalumab/placebo (once every 3 weeks, four cycles) presurgery and then adjuvant durvalumab/placebo (once every 4 weeks, 12 cycles). Efficacy was analyzed in the modified intention-to-treat population (n = 740; for DFS, its resected subpopulation), which excluded patients with documented <i>EGFR</i>/<i>ALK</i> aberrations. As of May 10, 2024 (median follow-up, 25.9 months [censored patients]), EFS benefit favoring the durvalumab arm remained consistent (hazard ratio [HR], 0.69 [95% CI, 0.55 to 0.88]). Numerical improvement in DFS (HR, 0.66 [95% CI, 0.47 to 0.92]) and OS (HR, 0.89 [95% CI, 0.70 to 1.14]) favored the durvalumab arm. Maximum grade 3/4 adverse events occurred in 15.4% and 10.6% of the durvalumab and placebo arms, respectively, during adjuvant treatment. These results further support perioperative durvalumab plus neoadjuvant chemotherapy as a new treatment option.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2502659"},"PeriodicalIF":44.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850619","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":"Targeting ErbB-Family Receptors in Small Cell Lung Cancer: Clinical Activity and an Unresolved Mechanism.","authors":"Junko Tanizaki","doi":"10.1200/JCO-26-01469","DOIUrl":"https://doi.org/10.1200/JCO-26-01469","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601469"},"PeriodicalIF":44.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840535","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":"Reply to: Prior BRAF Inhibitor Exposure Is Not Enough to Define Resistance in the Phase I Mosperafenib Study.","authors":"Maria Vieito, Elisa Fontana, Gabriel Schnetzler, David Dejardin, Florian Renner, Andreas Roller, Nino Keshelava","doi":"10.1200/JCO-26-01636","DOIUrl":"https://doi.org/10.1200/JCO-26-01636","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601636"},"PeriodicalIF":44.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840519","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":"Long-Term Survival Outcomes of Modified-FOLFOXIRI Plus Cetuximab Versus Bevacizumab in <i>RAS</i>/<i>BRAF</i> Wild-Type Metastatic Colorectal Cancer: Final Analysis of the DEEPER Trial.","authors":"Yu Sunakawa, Manabu Shiozawa, Takanori Watanabe, Hirofumi Ota, Hisateru Yasui, Taichi Yabuno, Mitsuyoshi Tei, Mitsugu Kochi, Dai Manaka, Hisatsugu Ohori, Tatsuro Yamaguchi, Tamotsu Sagawa, Masahito Kotaka, Yutaro Kubota, Takashi Sekikawa, Masato Nakamura, Masahiro Takeuchi, Wataru Ichikawa, Masashi Fujii, Akihito Tsuji","doi":"10.1200/JCO-26-00355","DOIUrl":"https://doi.org/10.1200/JCO-26-00355","url":null,"abstract":"<p><p>The randomized phase II DEEPER trial (jRCTs061180022) previously reported superior depth of response with modified 5-fluorouracil, leucovorin, oxaliplatin and irinotecan (m-FOLFOXIRI) plus cetuximab versus bevacizumab in patients with <i>RAS</i> wild-type metastatic colorectal cancer (mCRC). Here, we report updated final survival outcomes and exploratory subgroup analyses focusing on <i>RAS</i>/<i>BRAF</i> wild-type and left-sided tumors. Final overall survival (OS) and progression-free survival (PFS) were analyzed in the per-protocol set (PPS) with exploratory subgroup analyses according to the presence of liver-limited disease and sex, using extended follow-up data. There were no differences in PFS and OS in the PPS. In patients with <i>RAS</i>/<i>BRAF</i> wild-type and left-sided tumors, median PFS was longer with cetuximab than with bevacizumab (14.8 <i>v</i> 11.9 months; hazard ratio [HR], 0.71 [95% CI, 0.52 to 0.97]; <i>P</i> = .029). The median OS was 50.2 months for cetuximab and 40.2 months for bevacizumab (HR, 0.74 [95% CI, 0.53 to 1.05]). In the exploratory analyses, cetuximab-based therapy was associated with longer OS in male patients (HR, 0.59; <i>P</i> = .016) and in patients with extrahepatic disease (HR, 0.60; <i>P</i> = .014). In conclusion, the DEEPER trial suggests that m-FOLFOXIRI plus cetuximab achieves superior tumor shrinkage and may be associated with favorable outcomes in selected patients with <i>RAS</i>/<i>BRAF</i> wild-type and left-sided mCRC, with exploratory signals of benefit in male patients and those with extrahepatic disease.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600355"},"PeriodicalIF":44.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840465","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":"Refined Continuous Risk Index for Accurately Predicting Outcomes of Patients With Chronic Lymphocytic Leukemia After Limited-Duration Therapy.","authors":"Othman Al-Sawaf, Can Zhang, Mohammad S Esfahani, Chih Long Liu, Sandra Robrecht, Eugen Tausch, Anke Schilhabel, Matthias Ritgen, Christof Schneider, Martin Peifer, Moritz Fürstenau, Carsten Utoft Niemann, Arnon P Kater, John F Seymour, Brenda Chyla, Yanwen Jiang, Barbara Eichhorst, Stephan Stilgenbauer, Michael Hallek, Ash A Alizadeh, David M Kurtz, Kirsten Fischer","doi":"10.1200/JCO-26-00161","DOIUrl":"https://doi.org/10.1200/JCO-26-00161","url":null,"abstract":"<p><strong>Purpose: </strong>Measurable residual disease (MRD) status after limited-duration treatment for chronic lymphocytic leukemia (CLL) strongly predicts survival times and is considered a surrogate end point. However, most prognostic indices, including the International Prognostic Index (CLL-IPI), rely solely on pretreatment features. To incorporate dynamic MRD data in prognostic models, the continuous individualized risk index (CIRI) was proposed in 2019. Since developed in the context of chemoimmunotherapy, we here propose a refined version of CIRI, in the context of fixed-duration targeted therapy, which includes MRD status at interim, end-of-treatment (EoT) and, in addition, 12-month post-EoT (CIRI2-CLL).</p><p><strong>Methods: </strong>After developing model parameters from the CLL8/10/11 and MURANO trials, we applied CIRI2-CLL to independent validation sets from the CLL14 (venetoclax-obinutuzumab <i>v</i> chlorambucil-obinutuzumab) and CLL13 (venetoclax-obinutuzumab with or without ibrutinib <i>v</i> chemoimmunotherapy) trials and assessed model calibration, stratification, and performance.</p><p><strong>Results: </strong>We compared CIRI2-CLL with individual indices and found good calibration with an approximately 5% difference between observed and predicted event probabilities for progression-free survival (PFS). CIRI2-CLL demonstrated superior performance compared with individual indices as measured by C-statistics between 0.82 and 0.98 at all time points, including MRD and CLL-IPI, improving PFS prediction by 14%-37% from 2 to 5 years. When stratifying patients by CIRI2-CLL into low-, intermediate-, and high-risk groups, the corresponding 3-year PFS rates were 100.0%, 70.2%, and 10.8%. Performance was maintained for overall survival.</p><p><strong>Conclusion: </strong>These results validate CIRI2-CLL in the context of limited-duration CLL therapy. Our approach suggests the models' adaptability to emerging additional longitudinal MRD and/or outcome data. By introducing CIRI2-CLL, we offer a dynamic tool for investigators to reliably identify patients with increased risk of disease relapse after limited-duration therapy with venetoclax and obinutuzumab, freely accessible at CIRI2 (Stanford University), with important implications for informed decision making and for future risk-adapted CLL trial design.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600161"},"PeriodicalIF":44.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840476","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":"Speeding to a Stop: Postapproval Barriers to Accessing New Lung Cancer Therapies.","authors":"Ibiayi Dagogo-Jack","doi":"10.1200/JCO-26-01480","DOIUrl":"https://doi.org/10.1200/JCO-26-01480","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601480"},"PeriodicalIF":44.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840554","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":"Prior BRAF Inhibitor Exposure Is Not Enough to Define Resistance in the Phase I Mosperafenib Study.","authors":"Changjiang Zhao, Ruiyu Luo, He Yan, Yufei Li","doi":"10.1200/JCO-26-00996","DOIUrl":"https://doi.org/10.1200/JCO-26-00996","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600996"},"PeriodicalIF":44.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840479","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}