Journal of Clinical Oncology最新文献

{"title":"DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish.","authors":"Samuel J Klempner, Mohamad Bassam Sonbol, Zev A Wainberg, Hope Elizabeth Uronis, Vi K Chiu, Aaron James Scott, Syma Iqbal, Mohamedtaki Abdulaziz Tejani, Vincent Chung, Melissa C Stilian, Mathis Thoma, Ying Zhang, Michael H Kagey, Jason Baum, Cynthia A Sirard, Rachel A Altura, Jaffer A Ajani","doi":"10.1200/JCO.24.00410","DOIUrl":"https://doi.org/10.1200/JCO.24.00410","url":null,"abstract":"<p><strong>Purpose: </strong>The outcomes of anti-PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study.</p><p><strong>Patients and methods: </strong>Patients had untreated human epidermal growth factor receptor 2-negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m² once every 3 weeks, and capecitabine 1,000 mg/m² twice daily on days 1-15 of each 21-day cycle. The primary end point was safety and tolerability. Key secondary end points included objective response rate (ORR) by RECISTv1.1, progression-free survival (PFS), and overall survival (OS).</p><p><strong>Results: </strong>Between September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%.</p><p><strong>Conclusion: </strong>DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801).</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466553","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":"How to Test <i>HER2</i> for Predicting Resistance to Anti-Epidermal Growth Factor Receptor Therapy in Metastatic Colorectal Cancer? Evidence From the Secondary Analysis of Biomarkers of CALGB/SWOG 80405.","authors":"Andrea Sartore-Bianchi, Silvia Marsoni, Alessio Amatu, Valter Torri, Emanuela Bonoldi, Alberto Bardelli, Livio Trusolino, Salvatore Siena","doi":"10.1200/JCO.24.00805","DOIUrl":"10.1200/JCO.24.00805","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855580","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":"Academic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer.","authors":"Marleen Kok, Robbert-Jan Gielen, Sylvia Adams, Jochen K Lennerz, Priyanka Sharma, Sibylle Loibl, Erin Reardon, Gabe Sonke, Sabine Linn, Suzette Delaloge, Denis Lacombe, Tim Robinson, Sunil Badve, Miguel Martin, Justin M Balko, Michail Ignatiadis, Giuseppe Curigliano, Antonio C Wolff, Elizabeth A Mittendorf, Sherene Loi, Lajos Pusztai, Sara M Tolaney, Roberto Salgado","doi":"10.1200/JCO.24.00372","DOIUrl":"10.1200/JCO.24.00372","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748333","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":"Utility of the 70-Gene MammaPrint Assay for Prediction of Benefit From Extended Letrozole Therapy in the NRG Oncology/NSABP B-42 Trial.","authors":"Priya Rastogi, Hanna Bandos, Peter C Lucas, Laura J van 't Veer, Jia-Perng J Wei, Charles E Geyer, Louis Fehrenbacher, Stephen K L Chia, Adam M Brufsky, Janice M Walshe, Gamini S Soori, Shaker R Dakhil, Soonmyung Paik, Sandra M Swain, Andrea R Menicucci, M William Audeh, Norman Wolmark, Eleftherios P Mamounas","doi":"10.1200/JCO.23.01995","DOIUrl":"10.1200/JCO.23.01995","url":null,"abstract":"<p><strong>Purpose: </strong>MammaPrint (MP) determines distant metastatic risk and may improve patient selection for extended endocrine therapy (EET). This study examined MP in predicting extended letrozole therapy (ELT) benefit in patients with early-stage breast cancer (BC) from the NSABP B-42 trial.</p><p><strong>Patients and methods: </strong>MP was tested in 1,866 patients randomly assigned to receive ELT or placebo. The primary end point was distant recurrence (DR). Secondary end points were disease-free survival (DFS) and BC-free interval (BCFI). Tumors were classified as MP high risk (MP-HR) or low risk (MP-LR). MP-LR tumors were further classified as ultralow risk (MP-UL) or low non-ultralow risk (MP-LNUL).</p><p><strong>Results: </strong>There was no statistically significant difference in ELT benefit on DR between MP-HR and MP-LR (interaction <i>P =</i> .38). MP-LR tumors (n = 1,160) exhibited a statistically significant 10-year benefit of 3.7% for DR (hazard ratio [HR], 0.43 [95% CI, 0.25 to 0.74]; <i>P</i> = .002), whereas MP-HR tumors (n = 706) exhibited a nonsignificant 2.4% benefit (HR, 0.65 [95% CI, 0.34 to 1.24]; <i>P</i> = .19). The 10-year ELT benefit was significant for DFS (7.8%) and BCFI (7.0%) for MP-LR tumors, whereas MP-HR tumors did not significantly benefit (interaction DFS: <i>P</i> = .015, BCFI: <i>P</i> = .006). In exploratory analysis, the 10-year ELT benefit was significant and more pronounced in MP-LNUL (n = 908) tumors: 4.0% for DR, 9.5% for DFS, and 7.9% for BCFI; the benefit in MP-UL (n = 252) tumors was not significant: 3% for DR, 1.8% for DFS, and 4.1% for BCFI.</p><p><strong>Conclusion: </strong>The primary hypothesis of predictive ability of MP on DR was not confirmed. However, the secondary outcomes demonstrated MP was predictive of ELT response and identified a subset of patients with early-stage hormone receptor-positive BC (MP-LR) with improved outcomes from ELT. These data could have important clinical implications in patient selection beyond clinical risk assessment for EET.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758999","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 A. Sartore-Bianchi et al.","authors":"Francesca Battaglin, Fang-Shu Ou, Federico Innocenti, Heinz-Josef Lenz","doi":"10.1200/JCO.24.01086","DOIUrl":"10.1200/JCO.24.01086","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855583","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":"Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.","authors":"Michael D Jain, Jay Y Spiegel, Loretta J Nastoupil, John Tamaresis, Armin Ghobadi, Yi Lin, Lazaros Lekakis, Patrick Reagan, Olalekan Oluwole, Joseph McGuirk, Abhinav Deol, Kathleen A Dorritie, Alison R Sehgal, Andre Goy, Brian T Hill, Charalambos Andreadis, Javier Munoz, Matthew Ulrickson, Jason Westin, Julio C Chavez, Dilan Patel, Miriam T Jacobs, Radhika Bansal, N Nora Bennani, Vivek G Patel, Aaron P Rapoport, Julie M Vose, David B Miklos, Sattva S Neelapu, Frederick L Locke, Matthew Lunning, Saurabh Dahiya","doi":"10.1200/JCO.23.02786","DOIUrl":"10.1200/JCO.23.02786","url":null,"abstract":"<p><strong>Purpose: </strong>Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy.</p><p><strong>Methods: </strong>We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events.</p><p><strong>Results: </strong>Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (<i>P</i> = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; <i>P</i> < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2).</p><p><strong>Conclusion: </strong>In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878772","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":"Erratum: Surveillance Imaging After Curative-Intent Treatment for Cancer: Benefits, Harms, and Evidence.","authors":"","doi":"10.1200/JCO-24-01942","DOIUrl":"10.1200/JCO-24-01942","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288214","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":"Is Histopathology Deep Learning Artificial Intelligence the Future of Precision Oncology?","authors":"Vincent M Wagner","doi":"10.1200/JCO-24-01271","DOIUrl":"10.1200/JCO-24-01271","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288221","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":"Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From <i>EGFR</i> and <i>ALK</i> Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC).","authors":"Luke R G Pike, Emily Miao, Lillian A Boe, Tejas Patil, Brandon S Imber, Nathaniel J Myall, Erqi L Pollom, Caressa Hui, Vera Qu, Jacob Langston, Veronica Chiang, Michael Grant, Sarah B Goldberg, Joshua D Palmer, Rahul N Prasad, Tony J C Wang, Albert Lee, Catherine A Shu, Lanyi Nora Chen, Nicholas J Thomas, Steve E Braunstein, Brian D Kavanagh, D Ross Camidge, Chad G Rusthoven","doi":"10.1200/JCO.23.02668","DOIUrl":"10.1200/JCO.23.02668","url":null,"abstract":"<p><strong>Purpose: </strong>Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (<i>EGFR</i>) mutations and anaplastic lymphoma kinase (<i>ALK</i>) rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.</p><p><strong>Materials and methods: </strong>Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States. Time-to-CNS progression and overall survival (OS) were analyzed, with multivariable adjustment in Fine & Gray and Cox proportional hazards models for clinically relevant factors.</p><p><strong>Results: </strong>From 2013 to 2022, 317 patients were identified (200 TKI-only and 117 TKI + SRS). Two hundred fifty (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients receiving TKI + SRS were more likely to have BM ≥1 cm (<i>P</i> < .001) and neurologic symptoms (<i>P</i> < .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41 <i>v</i> 40 months, respectively; <i>P</i> = .5). On multivariable analysis, TKI + SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR], 0.63 [95% CI, 0.42 to 0.96]; <i>P</i> = .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55]; <i>P</i> < .001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI + SRS in patients with BM ≥1 cm in diameter for time-to-CNS progression and CNS progression-free survival.</p><p><strong>Conclusion: </strong>The addition of up-front SRS to CNS-penetrant TKI improved time-to-CNS progression and local CNS control, but not OS, in patients with BM from EGFR<i>-</i> and ALK-driven NSCLC. Patients with larger BM (≥1 cm) may benefit the most from up-front SRS.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758997","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":"Just Humor Me.","authors":"Stacey A Hubay","doi":"10.1200/JCO.24.00791","DOIUrl":"10.1200/JCO.24.00791","url":null,"abstract":"<p><p>Cancer isn't funny but sometimes a cancer clinic can be a surprisingly funny place.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288222","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}