Journal of Clinical Oncology最新文献

{"title":"Selpercatinib in <i>RET</i> Fusion-Positive Non-Small Cell Lung Cancer: Final Safety and Efficacy, Including Overall Survival, From the LIBRETTO-001 Phase I/II Trial.","authors":"Oliver Gautschi, Keunchil Park, Benjamin J Solomon, Pascale Tomasini, Herbert H Loong, Filippo De Braud, Koichi Goto, Patrick Peterson, Scott Barker, Katherine Liming, Geoffrey R Oxnard, Bente Frimodt-Moller, Alexander Drilon","doi":"10.1200/JCO-24-02076","DOIUrl":"10.1200/JCO-24-02076","url":null,"abstract":"<p><p>LIBRETTO-001 (ClinicalTrials.gov identifier: NCT03157128) is a registrational phase I/II, single-arm, open-label trial of selpercatinib in RET-dependent cancers. With 19 months of additional follow-up, we report the final efficacy and safety results of selpercatinib in patients with <i>RET</i> fusion-positive non-small cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy (N = 247) or were treatment-naïve (N = 69). The objective response rate (ORR) was 62% for pretreated patients and 83% for treatment-naïve patients. Duration of response (DoR) was 31.6 months for pretreated and 20.3 months for treatment-naïve patients (median follow-up approximately 38 months). Median progression-free survival (PFS) was 26.2 months for pretreated and 22.0 months for treatment-naïve patients (median follow-up approximately 40 months). Median overall survival was 47.6 months in pretreated patients and was not reached in the treatment-naïve group (median follow-up approximately 43 months). At the 3-year landmark estimate, 57% of pretreated and 66% of treatment-naïve patients were alive. Among 26 patients with measurable CNS metastases at baseline, the CNS-ORR was 85% with a CNS-DoR of 9.4 months and CNS-PFS of 11.0 months. The safety profile of selpercatinib was consistent with previous reports. With substantial additional follow-up, selpercatinib continued to show durable responses and intracranial activity, with a manageable safety profile in patients with <i>RET</i> fusion-positive NSCLC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1758-1764"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472417","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}

{"title":"Reply to: Treatment Intensification Based on Residual Disease in Elderly Patients With AML.","authors":"Nigel H Russell, Abin Thomas, Sylvie D Freeman","doi":"10.1200/JCO-25-00198","DOIUrl":"10.1200/JCO-25-00198","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1841-1843"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527813","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":"Challenges in Assessing Response in Clinical Trials for Neurofibromatosis Type 1 Plexiform Neurofibromas.","authors":"Eva Dombi, Andrea M Gross, Brigitte C Widemann, Brian D Weiss, Scott R Plotkin, Shivani Ahlawat","doi":"10.1200/JCO-24-02733","DOIUrl":"10.1200/JCO-24-02733","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1843-1844"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663607","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: Randomized Comparison of Magnetic Resonance Imaging Versus Transurethral Resection for Staging New Bladder Cancers: Results From the Prospective BladderPath Trial.","authors":"Richard T Bryan, Wenyu Liu, Sarah J Pirrie, Rashid Amir, Jean Gallagher, Shaista Hafeez, Ana I Hughes, Kieran P Jefferson, Allen Knight, Veronica Nanton, Harriet P Mintz, Ann M Pope, Jacob Cherian, Kingsley Ekwueme, Lyndon Gommersall, Giles Hellawell, Paul Hunter-Campbell, Gokul Kanda Swamy, Sanjeev Kotwal, Vivekanandan Kumar, David Mak, Amar Mohee, Thiagarajan Nambirajan, Douglas G Ward, Steven J Kennish, James W F Catto, Prashant Patel, Nicholas D James","doi":"10.1200/JCO-25-00779","DOIUrl":"10.1200/JCO-25-00779","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1847"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020182","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":"Entering the Era of Multidimensional Prognostication for Personalized Risk Assessment in Stage III Colon Cancer.","authors":"Benoit Rousseau, Andrea Cercek","doi":"10.1200/JCO-25-00205","DOIUrl":"10.1200/JCO-25-00205","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1751-1754"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994524","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}

{"title":"High-Dose Methotrexate in Children and Young Adults With ALL and Lymphoblastic Lymphoma: Results of the Randomized Phase III Study UKALL 2011.","authors":"Amy A Kirkwood, Nicholas Goulden, John Moppett, Sujith Samarasinghe, Rachael Hough, Clare Rowntree, Sarah Lawson, Pam Kearns, Anna Lawson, Ajay Vora","doi":"10.1200/JCO-24-01851","DOIUrl":"10.1200/JCO-24-01851","url":null,"abstract":"<p><strong>Purpose: </strong>UKALL 2011 randomly assigned children and young adults (younger than 25 years) with ALL or lymphoblastic lymphoma. The aims were to reduce induction toxicity (randomization 1 [R1]), CNS relapse risk (randomization 2 [R2]-interim maintenance [R2IM]), and maintenance morbidity (R2pulses).</p><p><strong>Methods: </strong>R1 compared induction dexamethasone (dex) for 28 days (6 mg/m²; standard) with 14 days (10 mg/m²; short). R2 was a factorial randomization resulting in four arms: high-dose methotrexate (HDM) with pulses, HDM without pulses, standard interim maintenance (SIM) with pulses (standard of care), and SIM without pulses. The primary end points were reduction in steroid-related toxicity (R1), CNS relapse rate (CNSR, R2IM), and bone marrow relapse rate (BMR, R2pulses; ALL only, noninferiority margin 5%). Event-free survival (EFS) was an additional primary end point for both randomizations.</p><p><strong>Results: </strong>Of 2,750 eligible patients registered between April 2012 and December 2018, 1,902 were randomly assigned to R1 and 1,570 to R2. Median follow-up is 99 (R1) and 87 months (R2). There were no differences in steroid-related toxicity between short and standard dex (23.8% <i>v</i> 25.5%; <i>P</i> = .41) and CNSR between SIM and HDM (0.98 [95% CI, 0.65 to 1.49]; <i>P</i> = .94; 5-year rates: SIM 5.3% and HDM 5.5%). EFS was no different between R1 and R2IM arms. BMR in the no pulses arm was noninferior (+1.7% increase at 5 years [95% CI, -1.5 to 4.1]; hazard ratio [HR], 1.19 [95% CI, 0.87 to 1.62]; <i>P</i> = .27). Although the EFS in the no pulses arm was inferior (1.34 [95% CI, 1.05 to 1.73]; <i>P</i> = .021), this was not significant for relapse (HR, 1.24 [95% CI, 0.96 to 1.62]; <i>P</i> = .10).</p><p><strong>Conclusion: </strong>Shorter duration of induction dex does not reduce steroid-related toxicity and HDM does not improve CNSR within a UKALL treatment backbone. Omission of pulses is noninferior for BMR.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1810-1823"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803405","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}

{"title":"Reply to: Challenges in Assessing Response in Clinical Trials for Neurofibromatosis Type 1 Plexiform Neurofibromas.","authors":"Christopher L Moertel, Angela C Hirbe, Laura J Klesse, P Leia Nghiemphu, Dusica Babovic-Vuksanovic, Timothy R Gershon","doi":"10.1200/JCO-25-00308","DOIUrl":"10.1200/JCO-25-00308","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1844-1846"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663609","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":"PRODIGE 29-UCGI 26 (NEOPAN): A Phase III Randomized Trial Comparing Chemotherapy With FOLFIRINOX or Gemcitabine in Locally Advanced Pancreatic Carcinoma.","authors":"Michel Ducreux,Romain Desgrippes,Yves Rinaldi,Frédéric Di Fiore,Rosine Guimbaud,Ludovic Evesque,Jean-Baptiste Bachet,Pierre Vanelslander,Thierry Lecomte,Olivier Capitain,Aurélie Parzy,Marion Bolliet,Pierre-Luc Etienne,Julien Forestier,Farid El Hajbi,Anne-Laure Bignon,Valérie Lebrun-Ly,Nicolas De Sousa Carvalho,Matthieu Texier,Olivier Bouche","doi":"10.1200/jco-24-02210","DOIUrl":"https://doi.org/10.1200/jco-24-02210","url":null,"abstract":"PURPOSEMore than 30% of patients with pancreatic cancer are unresectable because of the local extension with a median overall survival (OS) of <1 year. Combination of fluorouracil (FU), oxaliplatin, and irinotecan (FOLFIRINOX) is superior to gemcitabine in the treatment of metastatic pancreatic cancer, but standard of care remains gemcitabine in locally advanced pancreatic cancer (LAPC).METHODSPatients with histologically proven LAPC not suitable for surgery, Eastern Cooperative Oncology Group WHO performance status (PS) ≤1 were eligible. Random assignment was stratified by center, tumor localization (pancreas head yes/no), WHO PS (0 v 1), and age (≤60 years v >60 years). Patients received FOLFIRINOX or gemcitabine for 6 months. The primary end point was progression-free survival (PFS). Main secondary end points were OS, time to treatment failure, quality of life, and safety. One hundred seventy patients (142 events) were needed to detect an increase of 3 months in PFS with 80% power (log-rank test, 5% two-sided α).RESULTSOne hundred seventy one patients age 35-84 years were included and followed for a maximum of 5 years. With a median follow-up of 59.6 months (95% CI, 42.3 to not reached), 168 events were observed and the median PFS was 9.7 months (95% CI, 7.0 to 11.7) with FOLFIRINOX versus 7.7 months (95% CI, 6.2 to 9.2) with gemcitabine, hazard ratio (HR), 0.7 (95% CI, 0.5 to 1.0), P = .04. The median OS was 15.7 months (95% CI, 11.9 to 20.4) in the FOLFIRINOX group versus 15.4 months (95% CI, 11.7 to 18.6) in the gemcitabine group, HR, 1.02 (95% CI, 0.73 to 1.43), P = .95.CONCLUSIONResults confirm that FOLFIRINOX improves PFS significantly compared with gemcitabine and is well tolerated in LAPC. No significant difference in OS was observed between both groups.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"122 1","pages":"JCO2402210"},"PeriodicalIF":45.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066794","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":"Phase II Study (NO LIMIT, WJOG13320G) of First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High Advanced Gastric or Esophagogastric Junction Cancer.","authors":"Hisato Kawakami,Shigenori Kadowaki,Akitaka Makiyama,Masahiro Tsuda,Kenro Hirata,Naotoshi Sugimoto,Nozomu Machida,Hiroki Hara,Hidekazu Hirano,Taito Esaki,Yoshito Komatsu,Shuichi Hironaka,Yukari Kobayashi,Kazuhiro Kakimi,Yasutaka Chiba,Narikazu Boku,Ichinosuke Hyodo,Kei Muro","doi":"10.1200/jco-24-02463","DOIUrl":"https://doi.org/10.1200/jco-24-02463","url":null,"abstract":"PURPOSEMicrosatellite instability-high (MSI-H) advanced gastric or esophagogastric junction cancer (AGC), accounting for 5%-6% of all AGC cases, has shown an enhanced responsiveness to immunotherapy. We performed a single-arm phase II study to evaluate the combination of nivolumab (NIVO) and low-dose (LD) ipilimumab (IPI) for first-line treatment of MSI-H AGC.PATIENTS AND METHODSPatients with MSI-H AGC received NIVO (240 mg once every 2 weeks) and IPI (1 mg/kg once every 6 weeks). The primary end point was overall response rate (ORR) assessed by blinded independent central review. Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and biomarker analysis. MSI-H status was confirmed with an MSI-IVD Kit (Falco).RESULTSTwenty-nine patients were enrolled. The ORR was 62.1% (95% CI, 42.3 to 79.3), with a complete response rate of 10.3%. The DCR was 79.3% (95% CI, 60.3 to 92.0). Treatment-related adverse events (TRAEs) of any grade occurred in 93.1% of patients, with those of grade ≥3 manifesting in 37.9% of patients. At the data cutoff (median follow-up of 9.0 months), treatment had been discontinued in 21 patients, with such discontinuation being due to TRAEs in 12 (41.4%) patients. However, after exclusion of one patient with progressive disease, the remaining 11 patients showed long-term antitumor efficacy after treatment discontinuation (range of response duration, 0.9+ to 15.6+ months). The median PFS was 13.8 months (95% CI, 13.7 months to not reached [NR]) and the median OS was NR (95% CI, 13.7 months to NR), with a 12-month OS rate of 79.5%.CONCLUSIONNIVO plus LD-IPI showed robust and durable antitumor efficacy as a first-line treatment for MSI-H AGC. Although TRAEs often led to treatment discontinuation, treatment efficacy was subsequently sustained in most patients.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"6 1","pages":"JCO2402463"},"PeriodicalIF":45.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066804","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":"Should We Screen for Malignancies in People With Ataxia Telangiectasia?","authors":"Rob A Dineen, A Ramsay Bowden","doi":"10.1200/JCO-25-00050","DOIUrl":"https://doi.org/10.1200/JCO-25-00050","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500050"},"PeriodicalIF":42.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078306","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}