Targeted Oncology最新文献

{"title":"Impact of AML1/ETO Fusion on the Efficacy of Venetoclax Plus Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia","authors":"Dian Jin, Haoguang Chen, Jingsong He, Yi Li, Gaofeng Zheng, Yang Yang, Yi Zhao, Jing Le, Wenxiu Shu, Donghua He, Zhen Cai","doi":"10.1007/s11523-024-01039-y","DOIUrl":"https://doi.org/10.1007/s11523-024-01039-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p><i>AML1/ETO</i> fusion confers favorable prognosis in acute myeloid leukemia (AML) treated with intensive chemotherapy (IC). However, the impact of <i>AML1/ETO</i> fusion on the efficacy of venetoclax in the treatment of AML is unclear.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The aim of this study was to evaluate the efficacy of venetoclax plus hypomethylating agents (VEN/HMAs) in patients with <i>AML1/ETO</i>-positive AML.</p><h3 data-test=\"abstract-sub-heading\">Patients and Methods</h3><p>Patients with newly diagnosed AML in two centers were reviewed and divided into three cohorts: <i>AML1/ETO</i>-positive AML treated with frontline VEN/HMA (Cohort A), <i>AML1/ETO</i>-negative AML treated with frontline VEN/HMA (Cohort B), or <i>AML1/ETO</i>-positive AML treated with frontline IC (Cohort C). The response and survival were compared between the cohorts.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 260 patients were included in the study. Patients in Cohort A had a significantly lower overall response rate (ORR) than patients in Cohort B (40.9% vs 71.2%, <i>p</i> = 0.005). The median event-free survival (EFS) in Cohort A and Cohort B was 2.7 months and 7.7 months, respectively, with no significant difference. The ORR and median EFS in Cohort C were 80.8% and 14.9 months, respectively, which were significantly superior to those in Cohort A, and the advantages remained significant after propensity score matching. ORR and EFS in <i>KIT</i>-mutated patients with <i>AML1/ETO</i>-positive AML receiving VEN/HMA were much inferior to those in <i>KIT</i> wild-type patients (ORR 0.0% vs 81.8%, <i>p</i> = 0.001; EFS 1.2 months vs not reached, <i>p</i> &lt; 0.001).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Newly diagnosed AML patients with <i>AML1/ETO</i> fusion had a poor response to frontline VEN/HMA treatment. When determining induction therapy for patients with <i>AML1/ETO</i>-positive AML, IC should be preferred over VEN/HM.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"55 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Lenvatinib Clinical Trials: A Systematic Review","authors":"Patrick Crotty, Karim Kari, Griffin K. Hughes, Chase Ladd, Ryan McIntire, Brooke Gardner, Andriana M. Peña, Sydney Ferrell, Jordan Tuia, Jacob Cohn, Alyson Haslam, Vinay Prasad, Matt Vassar","doi":"10.1007/s11523-024-01040-5","DOIUrl":"https://doi.org/10.1007/s11523-024-01040-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Importance</h3><p>Chemotherapy agents are typically initially tested in their most promising indications; however, following initial US FDA approval, new clinical trials are often initiated in less promising indications where patients experience a worse burden-benefit ratio. The current literature on the burden-benefit profile of lenvatinib in non-FDA-approved indications is lacking.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study aimed to evaluate published clinical trials of lenvatinib in order to determine the burden-benefit profile for patients over time.</p><h3 data-test=\"abstract-sub-heading\">Evidence Review</h3><p>On 25 May 2023, we searched the Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov databases for clinical trials of lenvatinib used to treat solid cancers. Eligible articles were clinical trials, containing adult participants, published in English, and involving solid tumors. Screening and data collection took place in a masked, duplicate fashion. For each eligible study, we collected adverse event data, trial characteristics, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Trials were classified as positive when meeting their primary endpoint and safety, negative (not meeting either criteria), or indeterminate (lacking prespecified primary endpoint).</p><h3 data-test=\"abstract-sub-heading\">Findings</h3><p>Expansion of clinical trial testing beyond lenvatinib’s initial FDA indication demonstrated a consistent rise in cumulative adverse events, along with a decline in drug efficacy. Lenvatinib was tested in 16 cancer indications, receiving FDA approval in 4. A total of 5390 Grade 3–5 adverse events were experienced across 6225 clinical trial participants. Expanded indication testing further demonstrated widely variable ORR (11–69%), OS (6.2–32 months), and PFS (3.6–15.7 months) across all indications. After initial FDA approval, clinical trial results in expanded indications were less likely to meet their primary endpoints, particularly among non-randomized clinical trials.</p><h3 data-test=\"abstract-sub-heading\">Conclusion and relevance</h3><p>Our paper evaluated the effectiveness of lenvatinib for its FDA-approved indications; however, expansion of clinical trials into novel indications was characterized by diminished efficacy, while patients experienced a high burden of adverse events consistent with lenvatinib’s established safety profile. Furthermore, clinical trials testing in novel indications was marked by repeated phase I and II clinical trials along with a failure to progress to phase III clinical trials. Future clinical trials using lenvatinib as an intervention should carefully evaluate the potential benefits and burden patients may experience.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"38 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Summary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC","authors":"Masahiro Tsuboi, Roy S. Herbst, Thomas John, Terufumi Kato, Margarita Majem, Christian Grohé, Jie Wang, Jonathan W. Goldman, Shun Lu, Filippo de Marinis, Frances A. Shepherd, Ki Hyeong Lee, Nhieu Thi Le, Arunee Dechaphunkul, Dariusz Kowalski, Laura Bonanno, Manuel Dómine, Lynne Poole, Ana Bolanos, Yuri Rukazenkov, Yi-Long Wu","doi":"10.1007/s11523-024-01034-3","DOIUrl":"https://doi.org/10.1007/s11523-024-01034-3","url":null,"abstract":"<p>This is a summary of the original article ‟Overall survival with osimertinib in resected EGFR-mutated NSCLC.ˮ Osimertinib blocks the activity of the epidermal growth factor receptor (EGFR) on cancer cells, causing cancer cell death and tumor shrinkage, and is an effective treatment for EGFR-mutated non-small cell lung cancer (NSCLC). The ADAURA study assessed the effects of osimertinib versus placebo in patients with EGFR-mutated (exon 19 deletion or L858R) early stage (IB–IIIA) NSCLC removed by surgery (resected). Previous results from ADAURA demonstrated that patients treated with osimertinib stayed alive and cancer-free (disease-free survival) significantly longer than patients who received placebo. Recent data showed the overall length of time patients were alive after starting treatment (overall survival). In both the primary stage II–IIIA and overall stage IB–IIIA populations, patients in the osimertinib group had a significant 51% reduction in the risk of death compared with the placebo group. The data demonstrated that osimertinib after surgery significantly improved overall survival in patients with resected, EGFR-mutated, stage IB–IIIA NSCLC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"61 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation Signatures Correlate with Response to Immune Checkpoint Inhibitors in Metastatic Melanoma.","authors":"Julia Maria Ressler, Erwin Tomasich, Teresa Hatziioannou, Helmut Ringl, Gerwin Heller, Rita Silmbrod, Lynn Gottmann, Angelika Martina Starzer, Nina Zila, Philipp Tschandl, Christoph Hoeller, Matthias Preusser, Anna Sophie Berghoff","doi":"10.1007/s11523-024-01041-4","DOIUrl":"10.1007/s11523-024-01041-4","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation profiles have emerged as potential predictors of therapeutic response in various solid tumors.</p><p><strong>Objective: </strong>This study aimed to analyze the DNA methylation profiles of patients with stage IV metastatic melanoma undergoing first-line immune checkpoint inhibitor treatment and evaluate their correlation with a radiological response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).</p><p><strong>Methods: </strong>A total of 81 tissue samples from 71 patients with metastatic melanoma (27 female, 44 male) were included in this study. We utilized Illumina Methylation EPIC Beadchips to retrieve their genome-wide methylation profile by interrogating >850,000 CpG sites. Clustering based on the 500 most differentially methylated genes was conducted to identify distinct methylation patterns associated with immune checkpoint inhibitor response. Results were further aligned with an independent, previously published data set.</p><p><strong>Results: </strong>The median progression-free survival was 8.5 months (range: 0-104.1 months), and the median overall survival was 30.6 months (range: 0-104.1 months). Objective responses were observed in 29 patients (40.8%). DNA methylation profiling revealed specific signatures that correlated with radiological response to immune checkpoint inhibitors. Three distinct clusters were identified based on the methylation patterns of the 500 most differentially methylated genes. Cluster 1 (12/12) and cluster 2 (12/24) exhibited a higher proportion of responders, while cluster 3 (39/45) predominantly consisted of non-responders. In the validation data set, responders also showed more frequent hypomethylation although differences in the data sets limit the interpretation.</p><p><strong>Conclusions: </strong>These findings suggest that DNA methylation profiling of tumor tissues might serve as a predictive biomarker for immune checkpoint inhibitor response in patients with metastatic melanoma. Further validation studies are warranted to confirm the efficiency of DNA methylation profiling as a predictive tool in the context of immunotherapy for metastatic melanoma.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"263-275"},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Adverse Events Between PARP Inhibitors in Patients with Epithelial Ovarian Cancer: A Nationwide Propensity Score Matched Cohort Study.","authors":"Gwan Hee Han, Hae-Rim Kim, Hee Yun, Jae-Hoon Kim, Hanbyoul Cho","doi":"10.1007/s11523-024-01037-0","DOIUrl":"10.1007/s11523-024-01037-0","url":null,"abstract":"<p><strong>Background: </strong>Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce.</p><p><strong>Objective: </strong>This study aimed to compare the safety of different PARPi in patients with EOC.</p><p><strong>Patients and methods: </strong>Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment. CEIs were identified using International Statistical Classification of Diseases (ICD) 9/10 codes, with additional outcomes being dose modification and persistence.</p><p><strong>Results: </strong>In the first-line maintenance treatment [118 niraparib, 104 olaparib (tablet) patients], no significant differences were noted in CEIs, dose reduction, or 6-month discontinuation rate. For second-line maintenance treatment [303 niraparib, 126 olaparib (tablet), and 675 olaparib (capsule) patients], niraparib was associated with a higher risk of hematologic CEIs, particularly anemia, compared with olaparib (tablet) (0.51 [0.26-0.98] and 0.09 [0.01-0.74], respectively), and higher rate of discontinuation rate at 6 months. Of note, patients over 60 years old showed an increased risk of CEIs with niraparib, as indicated by the hazard ratio divergence in restricted cubic spline plots.</p><p><strong>Conclusions: </strong>No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"251-262"},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sacituzumab Govitecan: A Review in Unresectable or Metastatic HR+/HER2- Breast Cancer.","authors":"Connie Kang","doi":"10.1007/s11523-024-01036-1","DOIUrl":"10.1007/s11523-024-01036-1","url":null,"abstract":"<p><p>Sacituzumab govitecan (TRODELVY^®) is a first-in-class trophoblast cell-surface antigen 2 (Trop-2)-directed antibody and topoisomerase I inhibitor conjugate that is approved globally as monotherapy for the treatment of adults with unresectable locally advanced or metastatic, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-; defined as immunohistochemistry 0, 1+ or 2+ and in situ hybridization-negative) breast cancer who have received endocrine-based therapy and ≥ 2 additional systemic therapies in the advanced setting. In the phase III TROPiCS-02 trial, intravenous sacituzumab govitecan demonstrated statistically significant and clinically meaningful improvements in progression-free survival and overall survival compared with physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) in adults with metastatic HR+/HER2- breast cancer. Sacituzumab govitecan had a generally manageable tolerability profile in these patients; the most common treatment-related grade ≥ 3 adverse events included neutropenia, diarrhoea, leukopenia, anaemia, fatigue and febrile neutropenia. Sacituzumab govitecan carries regulatory warnings for severe neutropenia and severe diarrhoea. Sacituzumab govitecan demonstrated an overall benefit in terms of health-related quality of life. Current evidence indicates that sacituzumab govitecan is an effective treatment option, with a generally manageable tolerability profile, for patients with pre-treated, unresectable locally advanced or metastatic HR+/HER2- breast cancer.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"289-296"},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival Benefit of Myeloablative Therapy with Autologous Stem Cell Transplantation in High-Risk Neuroblastoma: A Systematic Literature Review.","authors":"Urszula Żebrowska, Walentyna Balwierz, Jarosław Wechowski, Aleksandra Wieczorek","doi":"10.1007/s11523-024-01033-4","DOIUrl":"10.1007/s11523-024-01033-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Multimodal treatment of newly diagnosed high-risk neuroblastoma (HRNB) includes induction chemotherapy, consolidation with myeloablative therapy (MAT) and autologous stem cell transplantation (ASCT), followed by anti-disialoganglioside 2 (GD2) immunotherapy, as recommended by the Children's Oncology Group (COG) and the Society of Paediatric Oncology European Neuroblastoma (SIOPEN). Some centres proposed an alternative approach with induction chemotherapy followed by anti-GD2 immunotherapy, without MAT+ASCT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of this systematic literature review was to compare survival outcomes in patients with HRNB treated with or without MAT+ASCT and with or without subsequent anti-GD2 immunotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients and methods: &lt;/strong&gt;The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE via PubMed and EMBASE databases were systematically searched for randomised controlled trials (RCT) and observational comparative studies in patients with HRNB using search terms for 'neuroblastoma' and ('myeloablative therapy' OR 'stem cell transplantation'). Reporting of at least one survival outcome [event-free survival (EFS), progression-free survival, relapse-free survival and/or overall survival (OS)] was required for inclusion. Outcomes from RCTs were synthesized in meta-analysis, while meta-analysis of non-RCTs was not planned owing to expected heterogeneity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Literature searches produced 2587 results with 41 publications reporting 34 comparative studies included in the review. Of these, 7 publications reported 4 RCTs, and 34 publications reported 30 non-RCT studies. Studies differed with respect to included populations, induction regimen, response to induction, additional treatments and transplantation procedures. Subsequent treatments of relapse were rarely reported and could not be compared. In the meta-analysis, EFS was in favour of MAT+ASCT over conventional chemotherapy or no further treatment [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.67-0.91, p = 0.001] with a trend favouring MAT+ASCT for OS (HR = 0.86, 95% CI 0.73-1.00, p = 0.05). Tandem MAT+ASCT was found to improve EFS compared with the single procedure, with improvement in both EFS and OS in patients treated with anti-GD2 therapy. Non-RCT comparative studies were broadly consistent with evidence from the RCTs; however, not all reported survival benefits of MAT+ASCT (single or tandem). Limited comparative evidence on treatment without MAT+ASCT in patients treated with anti-GD2 immunotherapy suggests an increased risk of relapse. In relapsed patients, MAT+ASCT appears to improve OS, but evidence remains scarce.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Survival benefits in patients treated with MAT+ASCT confirm that the procedure should remain an integral part of multimodal therapy. In patients treated with anti-GD2 immunothe","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"143-159"},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different Genomic Clusters Impact on Responses in Advanced Biliary Tract Cancer Treated with Cisplatin Plus Gemcitabine Plus Durvalumab.","authors":"Margherita Rimini, Eleonora Loi, Mario Domenico Rizzato, Tiziana Pressiani, Caterina Vivaldi, Eleonora Gusmaroli, Lorenzo Antonuzzo, Erika Martinelli, Ingrid Garajova, Guido Giordano, Jessica Lucchetti, Marta Schirripa, Noemi Cornara, Federico Rossari, Francesco Vitiello, Elisabeth Amadeo, Mara Persano, Vittoria Matilde Piva, Rita Balsano, Francesca Salani, Chiara Pircher, Stefano Cascinu, Monica Niger, Lorenzo Fornaro, Lorenza Rimassa, Sara Lonardi, Mario Scartozzi, Patrizia Zavattari, Andrea Casadei-Gardini","doi":"10.1007/s11523-024-01032-5","DOIUrl":"10.1007/s11523-024-01032-5","url":null,"abstract":"<p><strong>Background: </strong>The results reported in the TOPAZ-1 phase III trial led to the approval of the combination of cisplatin and gemcitabine with durvalumab as the new first-line standard of care for patients with locally advanced or metastatic cholangiocarcinoma.</p><p><strong>Objective: </strong>We performed a clustering analysis to classify patients into different groups based on their mutation profile, correlating the results of the analysis with clinical outcomes.</p><p><strong>Methods: </strong>We selected 51 patients with cholangiocarcinoma who were treated with the combination of chemotherapy and durvalumab and who were screened using the next-generation sequencing-based FoundationOne gene panel. We conducted mutation-based clustering of tumors and a survival analysis.</p><p><strong>Results: </strong>Three main clusters were identified. Cluster 1 is mostly characterized by mutations in genes belonging to the chromatin modification pathway, altered in 100% of patients. Cluster 2 is characterized by the alteration of several pathways, among which DNA damage control, chromatin modification, RTK/RAS, cell-cycle apoptosis, TP53, and PI3K were the most affected. Finally, most altered pathways in cluster 3 were RTK/RAS and cell-cycle apoptosis. Overall response rate was 4/13 (31%), 12/24 (50%), and 0/10 (0%) in cluster 1, cluster 2, and cluster 3, respectively, and the difference between the three clusters was statistically significant (p = 0.0188).</p><p><strong>Conclusions: </strong>By grouping patients into three clusters with distinct molecular and genomic alterations, our analysis showed that patients included in cluster 2 had higher overall response rates, whereas patients included in cluster 3 had no objective response. Further investigations on larger and external cohorts are needed in order to validate our results.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"223-235"},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR and ERBB2 Exon 20 Insertion Mutations in Chinese Non-small Cell Lung Cancer Patients: Pathological and Molecular Characterization, and First-Line Systemic Treatment Evaluation.","authors":"Ruiying Zhao, Jiaqi Li, Lianying Guo, Chan Xiang, Shengnan Chen, Jikai Zhao, Jinchen Shao, Lei Zhu, Min Ye, Gang Qin, Tianqing Chu, Yuchen Han","doi":"10.1007/s11523-024-01042-3","DOIUrl":"10.1007/s11523-024-01042-3","url":null,"abstract":"<p><strong>Background: </strong>Data from studies looking at both EGFR and ERBB2 exon 20 insertion mutations (-20ins) in the same cohort of patients with non-small cell lung cancer (NSCLC) are limited.</p><p><strong>Objective: </strong>The purpose of this study was to analyze EGFR/ERBB2-20ins in all-stage NSCLC patients to reveal their histological and molecular features, and to retrospectively evaluate the results of first-line real-world systemic treatments in patients with advanced-stage disease.</p><p><strong>Patients and methods: </strong>We collected 13,920 formalin-fixed paraffin-embedded NSCLC specimens. Clinicopathological features were recorded and DNA-based next-generation sequencing was performed. First-line systemic treatment data were obtained via chart review.</p><p><strong>Results: </strong>In total, 414 (2.97%) EGFR-20ins cases and 666 (4.78%) ERBB2-20ins cases were identified. Both were more common in women, non-smokers, and patients with adenocarcinoma. The incidence of EGFR/ERBB2-20ins in adenocarcinoma is inversely proportional to the degree of invasion; 77 and 26 variants were detected in EGFR-20ins and ERBB2-20ins cases, respectively. The most common concurrently mutated genes were TP53 and RB1. In invasive adenocarcinoma, lepidic components were more common in EGFR/ERBB2-20ins-alone cases than in those with other concurrent mutated genes. In EGFR-/ERBB2-20ins patients, there was no significant difference in progression-free survival (PFS) or treatment response to first-line systemic treatments in this study. There was no significant difference in PFS or treatment response among patients with different EGFR/ERBB2-20ins variants and those with or without concurrent mutated genes.</p><p><strong>Conclusions: </strong>EGFR/ERBB2-20ins is more common in early lung adenocarcinoma. EGFR-20ins had more variants. In both cohorts, the results for first-line systemic treatments showed no significant difference.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"277-288"},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: An Exploratory Analysis of Real-World Data.","authors":"Alexander Olkus, Aurelie Tomczak, Anne Katrin Berger, Conrad Rauber, Philip Puchas, Cyrill Wehling, Thomas Longerich, Arianeb Mehrabi, De-Hua Chang, Jakob Liermann, Sophia Schäfer, Jan Pfeiffenberger, Dirk Jäger, Patrick Michl, Christoph Springfeld, Michael T Dill","doi":"10.1007/s11523-024-01044-1","DOIUrl":"10.1007/s11523-024-01044-1","url":null,"abstract":"<p><strong>Background: </strong>The combination of gemcitabine and cisplatin (gem/cis) with the anti-PD-L1-antibody durvalumab was recently approved as first line therapy for biliary tract cancer (BTC) based on the results of the TOPAZ-1 trial.</p><p><strong>Objective: </strong>We aim to analyse the feasibility and efficacy of the triple combination therapy in patients with BTC in a real-world setting and in correspondence with the genetic alterations of the cancer.</p><p><strong>Methods: </strong>In this single-centre retrospective analysis, all patients with BTC and treated with durvalumab plus gem/cis from April 2022 to September 2023 were included. Survival and treatment response were investigated, within the context of the inclusion and exclusion criteria of TOPAZ-1 and in correspondence with genetic alterations of the cancer.</p><p><strong>Results: </strong>In total, 35 patients, of which 51% met the inclusion criteria of the TOPAZ-1 trial, were analysed. Patients treated within TOPAZ-1 criteria did not have a significantly different median overall survival and progression free survival than the rest of the patients (10.3 versus 9.7 months and 5.3 versus 5 months, respectively). The disease control rate of patients within the TOPAZ-1 criteria was 61.1%, in comparison to 58.8% in the rest of patients. A total of 51 grade 3 and 4 adverse events were observed without significant differences in the subgroups. No specific correlating patterns of genetic alterations with survival and response were observed.</p><p><strong>Conclusions: </strong>The treatment of advanced patients with BTC with durvalumab and gem/cis, even beyond the inclusion criteria of the TOPAZ-1 trial, shows promising safety.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"213-221"},"PeriodicalIF":5.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}