Clinical Cancer Research最新文献

{"title":"INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab Plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma","authors":"Jérôme Fayette, Lisa Licitra, Kevin Harrington, Robert Haddad, Lillian L. Siu, Yi-Chun Liu, Makoto Tahara, Jean-Pascal Machiels, Danny Rischin, Tanguy Y. Seiwert, Robert L. Ferris, Ulrich Keilholz, Amanda Psyrri, Bhumsuk Keam, Paolo Bossi, Robert Metcalf, Ching-Yun Hsieh, Paul M.J. Clement, Pavel Isaev, Ali Mudunov, José Dinis, Ann Hoeben, Stefan Kasper, Konrad Klinghammer, Michael Hwang, Jorge Blando, Olivier Serrano, Dario Ruscica, Roger B. Cohen","doi":"10.1158/1078-0432.ccr-25-0073","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0073","url":null,"abstract":"Purpose: Treatment options for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) after failure of immune checkpoint inhibitor (ICI) treatment and platinum-based chemotherapy are limited. Preliminary data suggested monalizumab plus cetuximab had clinical activity in R/M HNSCC. Participants and methods: INTERLINK-1 (NCT04590963) was a double-blind, phase III study. Participants with R/M HNSCC who had received ICI therapy and progressed despite platinum-based chemotherapy were randomized 2:1 to monalizumab (750 mg, fortnightly) or placebo, plus cetuximab (400 mg/m2 loading dose, then 250 mg/m2, weekly). The primary endpoint was overall survival (OS) in participants with non-oropharyngeal cancer (OPC) or human papillomavirus (HPV)-negative OPC (HPV-unrelated analysis set). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). Results: At data cut-off, 216 participants were randomized in the HPV-unrelated analysis set; 145 to monalizumab plus cetuximab and 71 to placebo plus cetuximab. Median OS was 8.8 months for monalizumab plus cetuximab versus 8.6 months for placebo plus cetuximab (hazard ratio [HR], 1.00; 95% CI, 0.66–1.54); median PFS was 3.6 versus 3.8 months, respectively (HR, 1.11; 95% CI, 0.79–1.57); and ORR was 15.2% versus 23.9%, respectively. INTERLINK-1 was terminated after a preplanned interim analysis showed futility criteria were met (predetermined futility HR >0.874). Grade 3–4 treatment-related adverse events were reported in 18.3% and 17.2% of participants treated in the monalizumab and placebo arms, respectively. Conclusions: Monalizumab plus cetuximab did not improve OS compared with placebo plus cetuximab. The safety profile of the combination was consistent with safety observations for cetuximab monotherapy.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"9 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889622","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":"Clinical Implications of The Cancer Genome Atlas Molecular Classification System in Esophagogastric Cancer","authors":"Henry S. Walch, Raktim Borpatragohain, Justin Jee, Waleed Chatila, Christopher Fong, Steven B. Maron, Geoffrey Y. Ku, David H. Ilson, Yelena Y. Janjigian, Abraham J. Wu, Pari Shah, Daniel G. Coit, Manjit S. Bains, Valerie W. Rusch, Bernard J. Park, Matthew J. Bott, Katherine Gray, David R. Jones, Michael Berger, Nikolaus Schultz, Vivian E. Strong, Daniela Molena, Smita Sihag","doi":"10.1158/1078-0432.ccr-24-3473","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3473","url":null,"abstract":"Purpose: The Cancer Genome Atlas (TCGA) project defined four distinct molecular subtypes of esophagogastric adenocarcinoma: microsatellite instable (MSI), Epstein–Barr virus (EBV)–associated, genomically stable (GS), and chromosomally instable (CIN). However, an association between molecular subtypes and clinical outcomes has not been clearly demonstrated. Given few actionable biomarkers, we investigated the clinical relevance of TCGA classification system. Experimental Design: We identified all patients with esophagogastric adenocarcinoma whose tumors underwent prospective next-generation sequencing using the Memorial Sloan Kettering–IMPACT assay from 2014 to 2023. We classified all tumors in accordance with TCGA methodology and correlated molecular subtypes with high-quality clinicopathologic data. Results: Among 1,438 included patients, 941 had CIN, 344 had GS, 103 had MSI, and 50 had EBV tumors. Accounting for the clinical stage and tumor grade, molecular classification was independently associated with overall cancer-specific survival (P < 0.001) on Cox multivariable analysis. Furthermore, genomic signatures, patient demographics, pathologic responses to neoadjuvant therapy, patterns of recurrence, and metastatic organotropism differed significantly by molecular subtype. Although most distal esophageal and gastroesophageal junction tumors were CIN, up to 25% of these included GS, MSI, or EBV subtypes in contrast to TCGA. Random forest machine learning demonstrated that the molecular subtype is more influential in predicting response to treatment than tumor location. Conclusions: Molecular classification is independently prognostic and may warrant inclusion in future staging and treatment guidelines. Routine molecular profiling is clinically feasible and may play a role in the management of patients to help guide appropriate treatment selection and clinical trial enrollment in the place of tumor location.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"72 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889592","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":"Spatial heterogeneity, stromal phenotypes, and therapeutic vulnerabilities in colorectal cancer peritoneal metastasis","authors":"Johnny Chin-Ann. Ong, Joseph J. Zhao, Ying Liu, Supriya Srivastava, Daryl K. A. Chia, Ying En Quek, Xiaonan Fan, Haoran Ma, Kie Kyon Huang, Taotao Sheng, Qiu Xuan Tan, Gillian Ng, Joey W. S. Tan, Jia-Ying Joey. Lee, Lit-Hsin Loo, Li Yen Chong, Xue Wen. Ong, Su Ting Tay, Takeshi Hagihara, Angie Tan, Craig Ryan Cecil Joseph, Melissa C. C. Teo, Josephine Hendrikson, Clara Y. L. Chong, Wanyu Guo, Claramae S. Chia, Jolene S.M. Wong, Chin Jin Seo, Mingzhe Cai, Yvonne Tay, Kevin M. S. Sim, Ryan Y. K. Tay, Robert Walsh, Marcello Guaglio, Federica Morano, Ming Teh, Huey Yew Jeffrey Lum, Tony K. H. Lim, Louis Vermeulen, Maarten F. Bijlsma, Kristiaan Lenos, Samuel J. Klempner, Joe P. S. Yeong, Wei Peng Yong, Filippo Pietrantonio, Patrick Tan, Raghav Sundar","doi":"10.1158/1078-0432.ccr-24-3780","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3780","url":null,"abstract":"Purpose: Peritoneal metastases (PM) in colorectal cancer (CRC) portend a poor prognosis. We sought to elucidate molecular features differentiating primary tumors (PTs) from PMs and actionable targets facilitating transcoelomic dissemination and progression. Experimental Design: We performed multi-omic profiling of 227 samples from 136 patients, including 56 primary tumor (PT) and 120 synchronous PMs comprising 34 matched PT-PM pairs. Whole exome, and bulk RNA-seq analysis was conducted to identify underlying genomic aberrations and transcriptomic differences between primary and peritoneal lesions. We spatially characterized the microenvironment of tumor-stroma compartments and studied the roles of stromal phenotypes in promulgating tumorigenesis. Results: Whole exome sequencing found genomic alterations and clonality patterns between PTs and PMs remain broadly similar. Transcriptomic profiles however, suggest a transition as tumors reach the peritoneum towards a more mesenchymal tumor profile and fibrotic tumor microenvironment. Applying spatial profiling, we identify a fibro-collagenous and immune-infiltrated stromal phenotype (stromal cluster [SC] 2) characterized by increased cancer-associated fibroblasts, memory B cells, M2 macrophages and T-cell exhaustion. These findings were orthogonally validated by multiplex immunohistochemistry. Patients with SC2 stroma had poorer survival and were characterized by high SERPINE-1 (PAI-1) expression. PM in patients with SC2 stroma were associated with enriched oncogenic pathways such as TGF-β. PAI-1 inhibition of CRC PM cell-lines with a novel biologic demonstrated reduced IL2-STAT5 and TGF-β pathways and cell death. Conclusions: Our findings unveil distinctive and actionable molecular signatures, offering deeper insights into the intricate crosstalk between tumor cells and stromal microenvironments enabling PM in CRC.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"43 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889593","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":"Venetoclax plus modified-intensity Idarubicin and Cytarabine treatment as first-line treatment for newly diagnosed pediatric acute myeloid leukemia","authors":"Shiyuan Wang, Mingyan Jiang, Yaqin Wang, Lixian Chang, Beibei Zhao, Xiaoming Liu, Benquan Qi, Shuchun Wang, Tianfeng Liu, Xiaoyan Zhang, Yumei Chen, Fang Liu, Ye Guo, Xiaojuan Chen, Li Zhang, Yao Zou, Wenyu Yang, Ju Gao, Xiaofan Zhu, Min Ruan","doi":"10.1158/1078-0432.ccr-25-0479","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0479","url":null,"abstract":"Purpose: Venetoclax (VEN) has shown excellent activity in eliminating acute myeloid leukemia (AML) blasts in preclinical and clinical trials, but clinical data in pediatric newly diagnosed AML (ND-AML) remain limited. We evaluated VEN plus modified-intensity idarubicin and cytarabine chemotherapy (VIA) in childhood ND-AML. Experimental design: In an open-label, single-arm, multi-center prospective clinical trial, 65 ND-AML pediatric patients received VIA induction (VEN and modified-intensity cytarabine and idarubicin). Consolidation was guided on response to induction and individualized risk stratification. Primary end point was complete remission (CR) and measurable residual disease (MRD) response rates. Results: After induction cycle 1, CR and MRD negativity was 90.8% and 78.5%, increasing to 96.8% and 87.3% following induction cycle 2. 28 (43.2%) patients underwent hematopoietic stem cell transplantation (HSCT) without engraftment failure. CBF AML [t(8;21) and inv(16)/t(16;16)] patients achieved a favorable response rate, but the median log10 reduction of transcript levels was suboptimal [-1.7 (cycle 1) and -2.6 (cycle 2) for RUNX1::RUNX1T1, -2.3 and -2.5 for CBFB::MYH11]. Disease relapse was frequently observed in KIT mutation, RUNX1::RUNX1T1 and CBFB::MYH11. The most common grade 3-4 toxicities were hematological toxicities and febrile neutropenia (FN). No treatment-related deaths occurred. With a median follow-up of 15.7 months, the estimated 12-month overall survival and event-free survival was 92.3% (95% CI 86.0-99.8) and 79.1% (95% CI 69.6-90.0). MRD negativity post cycle 1 correlated with superior long-term survival (P < 0.001). Conclusions: VIA regimen is highly effective and relatively safe in children with ND-AML, with deep remission and favorable survival outcomes.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"34 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884655","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":"Antibody Drug Conjugates in Non-Small Cell Lung Cancer: Where is the Target and the Biomarker?","authors":"Fred R. Hirsch","doi":"10.1158/1078-0432.ccr-25-0839","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0839","url":null,"abstract":"ADCs are an emerging treatment of NSCLC. Some do not require biomarkers, while others require mutations and/or protein expression. New diagnostic technologies give opportunities for better target identification and selection of patients. Combination therapies might broaden relevant patient populations but might call for combined biomarker selection paradigms.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"35 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884505","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":"Pretargeting: Bridging the two worlds of radiopharmaceutical probes","authors":"Yuriko Mori, Jens Cardinale, Frederik L. Giesel","doi":"10.1158/1078-0432.ccr-25-0568","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0568","url":null,"abstract":"The human trophoblast cell-surface antigen 2 (Trop-2) is expressed in a variety of malignant diseases. Using pretargeting methodology, a novel antibody against Trop-2 was radiolabeled and evaluated in a preclinical setting. This showed promising characteristics lending itself as potential basis for further clinical trials as imaging agent and potential theranostic.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"43 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884654","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":"Predictive Effect of IGFBP-3 on Low-Dose Tamoxifen Efficacy in Noninvasive Breast Cancer in the Phase III Tam-01 Trial","authors":"Harriet Johansson, Debora Macis, Martino Oliva, Matteo Puntoni, Eva Blondeaux, Aliana Guerrieri-Gonzaga, Valentina Aristarco, Irene Maria Briata, Tania Buttiron-Webber, Luca Boni, Matteo Lazzeroni, Davide Serrano, Livia Giordano, Maria Digennaro, Laura Cortesi, Francesco Millo, Katia Cagossi, Giuseppe Aprile, Fabio Falcini, Elisa Gallerani, Bernardo Bonanni, Andrea DeCensi","doi":"10.1158/1078-0432.ccr-24-2987","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2987","url":null,"abstract":"Purpose: Low-dose tamoxifen 5 mg/day (babytam) for 3 years can decrease the incidence of new breast cancer events in women with breast intraepithelial neoplasia by 42% with limited toxicity, which provides a new treatment option for these disorders. However, predictive biomarkers of babytam efficacy are lacking. We studied whether baseline levels of insulin-like growth factor-1 (IGF-I), IGF-binding protein-3 (IGFBP-3), estradiol, and sex hormone–binding globulin (SHBG) and their ratios predict babytam efficacy on breast cancer events in a preplanned secondary analysis. Patients and Methods: Within a 1:1 placebo-controlled, multicenter randomized trial of babytam or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ, 406 of 500 participants consented to blood sampling at baseline and at 1 and 3 years. Serum IGF-I, IGFBP-3, estradiol, and SHBG levels and their ratios were measured using chemiluminescent immunoassays. Biomarker changes were estimated using mixed-effects models, and incidence rate ratios were calculated after 10 years of follow-up with Poisson regression. Subgroup analyses were performed using an interaction test and subpopulation treatment effect pattern plot. Results: Baseline levels of IGFBP-3 in the three top quartiles (≥3.44 µg/mL), but not in the lower quartile, predicted greater babytam efficacy compared with placebo (Pinteraction = 0.006). Baseline IGF-I, estradiol, or SHBG levels were not predictive of babytam efficacy, whereas the IGF-I/IGFBP-3 ratio was borderline significant (Pinteraction = 0.067). Conclusions: High baseline levels of IGFBP-3 (≥3.44 µg/mL) predicted babytam efficacy and may help differentiate which women benefit most from this treatment.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"43 1","pages":"OF1-OF6"},"PeriodicalIF":11.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884690","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":"CHIP'ing Signal from Noise in Liquid Biopsy.","authors":"Elsa Bernard,Jean-Baptiste Micol","doi":"10.1158/1078-0432.ccr-25-0569","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0569","url":null,"abstract":"The presence of clonal hematopoiesis (CH) in cell-free DNA (cfDNA) analysis can distort the interpretation of results and impact cancer treatment decisions. This CCR Translations discusses the importance of distinguishing the origin of cfDNA variants as tumoral or hematopoietic and its potential clinical implications.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"258 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871976","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":"Leveraging Longitudinal Patient-Reported Outcomes Trajectories to Predict Survival in Non-Small-Cell Lung Cancer","authors":"Jiawei Zhou, Benyam Muluneh, Zhaoyang Wang, Huaxiu Yao, Jim H. Hughes","doi":"10.1158/1078-0432.ccr-25-0292","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0292","url":null,"abstract":"Purpose: Despite their potential, patient-reported outcomes (PRO) are often underutilized in clinical decision-making, especially when improvements in PRO do not align with clinical outcomes. This misalignment may result from insufficient analytical methods that overlook the temporal dynamics and substantial variability of PRO data. To address these gaps, we developed a novel approach to investigate the prognostic value of longitudinal PRO dynamics in non-small-cell lung cancer (NSCLC) using Lung Cancer Symptom Scale (LCSS) data. Methods: Longitudinal patient-reported LCSS data from 481 NSCLC participants in the placebo arm of a Phase III trial were analyzed. A population modeling approach was applied to describe PRO progression trajectories while accounting for substantial variability in the data. Associations between PRO model parameters and survival outcomes were assessed using Cox proportional hazards models. Model-informed PRO parameters were used to predict survival via machine learning. Results: A PRO progression model described LCSS dynamics and predicted a median time to symptom progression of 229 days (95% confidence interval [CI]: 15-583). Faster PRO progression rates were significantly associated with poorer survival (Hazard ratio [HR] 1.13, 95% CI: 1.076-1.18), while greater improved PRO effects by placebo/prior treatment correlated with improved survival (HR 0.93, 95% CI: 0.883-0.99). A machine learning model using PRO parameters achieved an AUC-ROC of 0.78, demonstrating their potential to predict overall survival. Conclusions: This study demonstrates that longitudinal PRO data can provide prognostic insights into survival in NSCLC. The findings support the use of PRO dynamics to improve clinical decision-making and optimize patient-centered treatment strategies.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867022","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":"Factors Associated with Disease Progression after Discontinuation of Immune Checkpoint Inhibitors for Immune-Related Toxicity in Patients with Advanced Non–Small Cell Lung Cancer","authors":"Federica Pecci, Rohit Thummalapalli, Stephanie L. Alden, Biagio Ricciuti, Joao V. Alessi, Arielle Elkrief, Hira Rizvi, Xinan Wang, Mark Jeng, Jacklynn V. Egger, Victor R. Vaz, Adriana Barrichello, Giuseppe Lamberti, Alessandro Di Federico, Valentina Santo, Guilherme Rossato de Almeida, Malini Gandhi, Phoebe Clark, Mizuki Nishino, Bruce E. Johnson, Matthew Hellmann, Adam J. Schoenfeld, Mark M. Awad","doi":"10.1158/1078-0432.ccr-24-2990","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2990","url":null,"abstract":"Purpose: Among patients with advanced non–small cell lung cancer (NSCLC) who discontinue immune checkpoint inhibitors (ICI) because of immune-related adverse events (irAE), post-discontinuation clinical outcomes and factors associated with disease progression after discontinuation are largely unknown. Experimental Design: Clinicopathologic data were abstracted from patients with advanced NSCLC who received ICI and discontinued treatment because of irAE. Factors associated with post-discontinuation progression-free survival (PFS) and post-discontinuation overall survival (OS) were evaluated. Results: Of 2,794 patients, 10% (N = 271) discontinued ICI because of irAE, and the median duration of ICI treatment before discontinuation for irAE was 5.9 months (range, 0.03–73.5). A longer treatment duration before discontinuation for irAE was associated with improved post-discontinuation outcomes: for patients on ICI for <3 months (N = 89), 3 to 6 months (N = 49), and >6 months (N = 133) before discontinuing for irAE, the median post-discontinuation PFS was 6.2, 13.9, and 25.8 months (P < 0.001), respectively, and the median post-discontinuation OS was 21.7, 42.7, and 86.9 months (P < 0.001), respectively. At multivariable analyses, predictors of longer post-discontinuation PFS were PD-L1 ≥ 50%, complete response/partial response (CR/PR) to treatment, and treatment duration before discontinuation between 3 to 6 months and >6 months; predictors of longer post-discontinuation OS were nonsquamous histology, CR/PR, and treatment duration before discontinuation >6 months. The use of immunosuppressive agents for toxicity management did not affect post-discontinuation outcomes. Conclusions: A longer treatment duration before discontinuation, a best objective response of CR/PR, PD-L1 ≥50%, and nonsquamous histology may help clinicians identify patients who may experience long-term disease control after discontinuation of ICI for irAE.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"28 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847082","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}