Journal of Clinical Oncology最新文献

{"title":"Lorlatinib Versus Crizotinib in Patients With Advanced <i>ALK</i>-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study.","authors":"Benjamin J Solomon, Geoffrey Liu, Enriqueta Felip, Tony S K Mok, Ross A Soo, Julien Mazieres, Alice T Shaw, Filippo de Marinis, Yasushi Goto, Yi-Long Wu, Dong-Wan Kim, Jean-François Martini, Rossella Messina, Jolanda Paolini, Anna Polli, Despina Thomaidou, Francesca Toffalorio, Todd M Bauer","doi":"10.1200/JCO.24.00581","DOIUrl":"10.1200/JCO.24.00581","url":null,"abstract":"<p><strong>Purpose: </strong>Lorlatinib improved progression-free survival (PFS) and intracranial activity versus crizotinib in patients with previously untreated, advanced, <i>ALK</i>-positive non-small cell lung cancer (NSCLC) in the phase III CROWN study. Here, we report long-term outcomes from CROWN after 5 years of follow-up.</p><p><strong>Methods: </strong>Two hundred ninety-six patients with <i>ALK</i>-positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses.</p><p><strong>Results: </strong>With a median follow-up for PFS of 60.2 and 55.1 months, respectively, median PFS was not reached (NR [95% CI, 64.3 to NR]) with lorlatinib and 9.1 months (95% CI, 7.4 to 10.9) with crizotinib (hazard ratio [HR], 0.19 [95% CI, 0.13 to 0.27]); 5-year PFS was 60% (95% CI, 51 to 68) and 8% (95% CI, 3 to 14), respectively. Median time to intracranial progression was NR (95% CI, NR to NR) with lorlatinib and 16.4 months (95% CI, 12.7 to 21.9) with crizotinib (HR, 0.06 [95% CI, 0.03 to 0.12]). Safety profile was consistent with that in prior analyses. Emerging new <i>ALK</i> resistance mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment.</p><p><strong>Conclusion: </strong>After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced <i>ALK</i>-positive NSCLC and set a new benchmark for targeted therapies in cancer.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179612","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":"Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer.","authors":"Alessandro D Santin, Bradley R Corr, Alexander Spira, Lyndsay Willmott, James Butrynski, Ka Yu Tse, Jilpa Patel, Sabeen Mekan, Tia Wu, Kai-Wen Lin, Peiwen Kuo, Ecaterina E Dumbrava","doi":"10.1200/JCO.23.02767","DOIUrl":"10.1200/JCO.23.02767","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with advanced endometrial cancer (EC) who progress on or after platinum-based therapy and immunotherapy have poor prognosis. We report efficacy and safety of sacituzumab govitecan (SG), a trophoblast cell-surface antigen 2 (Trop-2)-directed antibody-drug conjugate, in patients with advanced EC.</p><p><strong>Methods: </strong>TROPiCS-03 (ClinicalTrials.gov identifier: NCT03964727) is a multicohort, open-label, phase II basket study in patients with metastatic solid tumors. Eligible patients in the EC cohort received SG 10 mg/kg once on days 1 and 8 every 3 weeks. Primary end point was objective response rate (ORR) by investigator's assessment per RECIST v1.1. Secondary end points included clinical benefit rate (CBR; complete and partial response, and stable disease ≥6 months), duration of response (DOR), and progression-free survival (PFS) per investigator assessment, overall survival, and safety. Trop-2 expression of archival or baseline tumor specimens was analyzed by immunohistochemistry.</p><p><strong>Results: </strong>At data extraction date, 41 patients were enrolled. Median follow-up was 5.8 months (range, 0.7-19.3); median previous therapies was three (range, 1-6); and 85% of patients received previous chemotherapy and immunotherapy. ORR was 22% (95% CI, 11 to 38); CBR was 32% (95% CI, 18 to 48). Median DOR was 8.8 months (95% CI, 2.8 to not estimable); median PFS was 4.8 months (95% CI, 2.8 to 9.8). Trop-2 exploratory analysis was conducted retrospectively for 39 patients. Tumor Trop-2 protein was highly expressed in EC, showing limited correlation with efficacy. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 73% of patients. Study drug discontinuation due to TRAEs was 5%. Two deaths occurred, deemed unrelated to SG.</p><p><strong>Conclusion: </strong>Findings from TROPiCS-03 showed encouraging efficacy of SG with a manageable toxicity profile in a heavily pretreated population with advanced EC. Safety findings were consistent with the known SG safety profile.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859917","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":"Results From First-in-Human Phase I Dose-Escalation Study of a Novel Bicycle Toxin Conjugate Targeting EphA2 (BT5528) in Patients With Advanced Solid Tumors.","authors":"Babar Bashir, Judy S Wang, Gerald Falchook, Elisa Fontana, Hendrik-Tobias Arkenau, Louise Carter, Rachel Galot, Bristi Basu, Alastair Greystoke, Vivek Subbiah, Debra L Richardson, Hanna Orr, Gavin Bennett, Rajiv Sharma, Hongmei Xu, Paola Paganoni, Cong Xu, Carly Campbell, Meredith McKean","doi":"10.1200/JCO.23.01107","DOIUrl":"10.1200/JCO.23.01107","url":null,"abstract":"<p><strong>Purpose: </strong>BT5528 is a Bicycle Toxin Conjugate, a novel class of chemically synthesized molecules, comprising a bicyclic peptide targeting EphA2 tumor antigen, linked to a cytotoxin (monomethyl auristatin E [MMAE]). EphA2 is overexpressed in many solid tumors and contributes to oncogenesis, tumor-associated angiogenesis, and metastasis.</p><p><strong>Materials and methods: </strong>The primary objectives were to investigate the safety and tolerability of BT5528 and to define the maximum-tolerated dose, if observed, and recommended phase II dose (RP2D)/expansion dose. Dose escalation exploring once every week or once every 2 weeks administration of BT5528 employed a 3 + 3 dose-escalation design for the first two dose levels, followed by a Bayesian logistic regression model. Secondary and exploratory end points included preliminary efficacy and the pharmacokinetics of BT5528 and MMAE.</p><p><strong>Results: </strong>Forty-five patients were enrolled and received BT5528 doses between 2.2 mg/m² once every week to 10.0 mg/m² once every 2 weeks within the dose-escalation stage of the study. The most frequent BT5528-related adverse events (AEs) were nausea (44.4%), diarrhea (35.6%), and fatigue (33.3%), and the most common grade ≥3 BT5528-related AE was neutropenia/neutrophil count decrease (22.2%). Dose level 6.5 mg/m² once every 2 weeks was selected as a RP2D. At 6.5 mg/m² once every 2 weeks, the overall response rate was 6.7%, and the disease control rate was 20.0%. BT5528 and MMAE pharmacokinetics are generally dose proportional. BT5528 has a short half-life (0.4-0.7 hours), and the half-life of MMAE is longer (35-47 hours).</p><p><strong>Conclusion: </strong>BT5528 was well tolerated and demonstrated favorable and preliminary antitumor activity. We believe these data provide preliminary validation of a Bicycle Toxin Conjugate approach to EphA2 tumor antigen. The study is ongoing and is evaluating BT5528 as monotherapy at a RP2D of 6.5 mg/m² once every 2 weeks.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132866","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":"Safety, Efficacy, and Pharmacokinetics of SHR-A1811, a Human Epidermal Growth Factor Receptor 2-Directed Antibody-Drug Conjugate, in Human Epidermal Growth Factor Receptor 2-Expressing or Mutated Advanced Solid Tumors: A Global Phase I Trial.","authors":"Herui Yao, Min Yan, Zhongsheng Tong, Xinhong Wu, Min-Hee Ryu, John J Park, Jee Hyun Kim, Yahua Zhong, Yiming Zhao, Mark Voskoboynik, Yongmei Yin, Kan Liu, Andreas Kaubisch, Caigang Liu, Jian Zhang, Shouman Wang, Seock-Ah Im, Vinod Ganju, Minal Barve, Hui Li, Changsheng Ye, Amitesh C Roy, Li-Yuan Bai, Chia-Jui Yen, Shanzhi Gu, Yung-Chang Lin, Lingying Wu, Lequn Bao, Kaijing Zhao, Yu Shen, Shangyi Rong, Xiaoyu Zhu, Erwei Song","doi":"10.1200/JCO.23.02044","DOIUrl":"10.1200/JCO.23.02044","url":null,"abstract":"<p><strong>Purpose: </strong>SHR-A1811 is an antibody-drug conjugate composed of an anti-human epidermal growth factor receptor 2 (HER2) antibody trastuzumab, a cleavable linker, and a topoisomerase I inhibitor payload. We assessed the safety, tolerability, antitumor activity, and pharmacokinetics of SHR-A1811 in heavily pretreated HER2-expressing or mutated advanced solid tumors.</p><p><strong>Methods: </strong>This global, multi-center, first-in-human, phase I trial was conducted at 33 centers. Patients who had HER2-expressing or mutated unresectable, advanced, or metastatic solid tumors and were refractory or intolerant to standard therapies were enrolled. SHR-A1811 was administered intravenously at doses ranging from 1.0 to 8.0 mg/kg once every 3 weeks. The primary end points were dose-limiting toxicity, safety, and the recommended phase II dose.</p><p><strong>Results: </strong>From September 7, 2020, to February 27, 2023, 307 patients who had undergone a median of three (IQR, 2-5) previous treatment regimens in the metastatic setting received SHR-A1811 treatment. As of data cutoff (February 28, 2023), one patient from the 6.4 mg/kg group experienced dose-limiting toxicities (pancytopenia and colitis). The most common grade 3 or higher adverse events (AEs) included decreased neutrophil count (119 [38.8%]) and decreased WBC count (70 [22.8%]). Interstitial lung disease occurred in only eight (2.6%) patients. Serious AEs and deaths occurred in 70 (22.8%) and 13 (4.2%) patients, respectively. SHR-A1811 led to objective responses in 59.9% (184/307) of all patients, 76.3% (90/118) of HER2-positive breast cancer, 60.4% (55/91) of HER2 low-expressing breast cancer, and 45.9% (39/85 with evaluable tumor responses) of the 98 nonbreast tumors.</p><p><strong>Conclusion: </strong>SHR-A1811 exhibited acceptable tolerability, promising antitumor activity, and a favorable pharmacokinetic profile in heavily pretreated advanced solid tumors. The recommended phase II dose of 4.8 or 6.4 mg/kg was selected for various tumor types.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432059","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 C.T. Matava et al.","authors":"Sarah Alexander, John A Kairalla, Sumit Gupta, Emily Hibbitts, Hannah Weisman, Doralina Anghelescu, Naomi J Winick, Kevin R Krull, Wanda L Salzer, Michael J Burke, Lia Gore, Meenakshi Devidas, Leanne Embry, Elizabeth A Raetz, Stephen P Hunger, Mignon L Loh, Kristina K Hardy","doi":"10.1200/JCO-24-01244","DOIUrl":"10.1200/JCO-24-01244","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758973","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":"Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia.","authors":"Ti-Cheng Chang, Wenan Chen, Chunxu Qu, Zhongshan Cheng, Dale Hedges, Abdelrahman Elsayed, Stanley B Pounds, Mary Shago, Karen R Rabin, Elizabeth A Raetz, Meenakshi Devidas, Cheng Cheng, Anne Angiolillo, Pradyuamna Baviskar, Michael Borowitz, Michael J Burke, Andrew Carroll, William L Carroll, I-Ming Chen, Richard Harvey, Nyla Heerema, Ilaria Iacobucci, Jeremy R Wang, Sima Jeha, Eric Larsen, Leonard Mattano, Kelly Maloney, Ching-Hon Pui, Nilsa C Ramirez, Wanda Salzer, Cheryl Willman, Naomi Winick, Brent Wood, Stephen P Hunger, Gang Wu, Charles G Mullighan, Mignon L Loh","doi":"10.1200/JCO.23.02238","DOIUrl":"10.1200/JCO.23.02238","url":null,"abstract":"<p><strong>Purpose: </strong>Although cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 90%, ALL remains a leading cause of cancer death in children. Half of relapses arise in children initially classified with standard-risk (SR) disease.</p><p><strong>Materials and methods: </strong>To identify genomic determinants of relapse in children with SR ALL, we performed genome and transcriptome sequencing of diagnostic and remission samples of children with SR (n = 1,381) or high-risk B-ALL with favorable cytogenetic features (n = 115) enrolled on Children's Oncology Group trials. We used a case-control study design analyzing 439 patients who relapsed and 1,057 who remained in complete remission for at least 5 years.</p><p><strong>Results: </strong>Genomic subtype was associated with relapse, which occurred in approximately 50% of cases of <i>PAX5</i>-altered ALL (odds ratio [OR], 3.31 [95% CI, 2.17 to 5.03]; <i>P =</i> 3.18 × 10^-8). Within high-hyperdiploid ALL, gain of chromosome 10 with disomy of chromosome 7 was associated with favorable outcome (OR, 0.27 [95% CI, 0.17 to 0.42]; <i>P</i> = 8.02 × 10^-10; St Jude Children's Research Hospital validation cohort: OR, 0.22 [95% CI, 0.05 to 0.80]; <i>P</i> = .009), and disomy of chromosomes 10 and 17 with gain of chromosome 6 was associated with relapse (OR, 7.16 [95% CI, 2.63 to 21.51]; <i>P</i> = 2.19 × 10^-5; validation cohort: OR, 21.32 [95% CI, 3.62 to 119.30]; <i>P</i> = .0004). Genomic alterations were associated with relapse in a subtype-dependent manner, including alterations of <i>INO80</i> in <i>ETV6::RUNX1</i> ALL, <i>IKZF1</i>, and <i>CREBBP</i> in high-hyperdiploid ALL and <i>FHIT</i> in <i>BCR::ABL1</i>-like ALL. Genomic alterations were also associated with the presence of minimal residual disease, including <i>NRAS</i> and <i>CREBBP</i> in high-hyperdiploid ALL.</p><p><strong>Conclusion: </strong>Genetic subtype, patterns of aneuploidy, and secondary genomic alterations determine risk of relapse in childhood ALL. Comprehensive genomic analysis is required for optimal risk stratification.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909803","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":"Propofol, Anesthesia, and Neurocognitive Outcomes in Patients With Pediatric Leukemia: Are We Missing the Forest for the Trees?","authors":"Clyde T Matava, James Peyton, Britta S von Ungern-Sternberg, Caleb Ing","doi":"10.1200/JCO.24.00856","DOIUrl":"10.1200/JCO.24.00856","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758972","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":"New Benchmark for Targeted Therapies in Lung Cancer: Median Progression-Free Survival for Lorlatinib in Advanced ALK+ Non-Small Cell Lung Cancer Surpasses 5 years.","authors":"Christine M Lovly","doi":"10.1200/JCO.24.01147","DOIUrl":"10.1200/JCO.24.01147","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132865","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 Y.-Y. Qiu et al.","authors":"Huabin Hu, Jianwei Zhang, Lishuo Shi, Meijin Huang, Jianping Wang, Yanhong Deng","doi":"10.1200/JCO-24-01217","DOIUrl":"10.1200/JCO-24-01217","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758996","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":"Evaluation of CD3 and CD8 T-Cell Immunohistochemistry for Prognostication and Prediction of Benefit From Adjuvant Chemotherapy in Early-Stage Colorectal Cancer Within the QUASAR Trial.","authors":"Christopher J M Williams, Richard Gray, Robert K Hills, Michael Shires, Liping Zhang, Zuo Zhao, Tracie Gardner, Nancy Sapanara, Xiao-Meng Xu, Isaac Bai, Dongyao Yan, Andrea Muranyi, Sarah Dance, Faranak Aghaei, Gemma Hemmings, Michael Hale, Uday Kurkure, Christoph Guetter, Susan D Richman, Gordon Hutchins, Jenny F Seligmann, Nicholas P West, Shalini Singh, Kandavel Shanmugam, Philip Quirke","doi":"10.1200/JCO.23.02030","DOIUrl":"10.1200/JCO.23.02030","url":null,"abstract":"<p><strong>Purpose: </strong>High densities of tumor infiltrating CD3 and CD8 T-cells are associated with superior prognosis in colorectal cancer (CRC). Their value as predictors of benefit from adjuvant chemotherapy is uncertain.</p><p><strong>Patients and methods: </strong>Tumor tissue from 868 patients in the QUASAR trial (adjuvant fluorouracil/folinic acid <i>v</i> observation in stage II/III CRC) was analyzed by CD3 and CD8 immunohistochemistry. Pathologists, assisted by artificial intelligence, calculated CD3 and CD8 cell densities (cells/mm²) in the core tumor (CT) and invasive margin (IM). Participants were randomly partitioned into training and validation sets. The primary outcome was recurrence-free interval (RFI), 2-year RFI for assessment of biomarker-treatment interactions. Maximum-likelihood methods identified optimal high-risk/low-risk group cutpoints in the training set. Prognostic analyses were repeated in the validation set.</p><p><strong>Results: </strong>In the training set, the recurrence rate in the high-risk group was twice that in the low-risk group for all measures (CD3-CT: rate ratio [RR], 2.00, <i>P</i> = .0008; CD3-IM: 2.38, <i>P</i> < .00001; CD8-CT: 2.17, <i>P</i> = .0001; CD8-IM: 2.13, <i>P</i> = .0001). This was closely replicated in the validation set (RR, 1.96, 1.79, 1.72, 1.72, respectively). In multivariate analyses, prognostic effects were similar in colon and rectal cancers, and in stage II and III disease. Proportional reductions in recurrence with adjuvant chemotherapy were of similar magnitude in the high- and low-recurrence risk groups. Combining information from CD3-IM and CD3-CT (CD3 Score) generated high-, intermediate-, and low-risk groups with numbers needed to treat (NNTs) to prevent one disease recurrence being 11, 21, and 36, respectively.</p><p><strong>Conclusion: </strong>Recurrence rates in the high-risk CD3/CD8 groups are twice those in the low-risk groups. Proportional reductions with chemotherapy are similar, allowing NNTs derived in QUASAR to be updated using contemporary, nonrandomized data sets.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859919","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}