Targeted Oncology最新文献

{"title":"The Molecular Landscape of Gastric Cancers for Novel Targeted Therapies from Real-World Genomic Profiling","authors":"Hiroyuki Yamamoto, Hiroyuki Arai, Ritsuko Oikawa, Kumiko Umemoto, Hiroyuki Takeda, Takuro Mizukami, Yohei Kubota, Ayako Doi, Yoshiki Horie, Takashi Ogura, Naoki Izawa, Jay A. Moore, Ethan S. Sokol, Yu Sunakawa","doi":"10.1007/s11523-024-01052-1","DOIUrl":"https://doi.org/10.1007/s11523-024-01052-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Panel-based comprehensive genomic profiling is used in clinical practice worldwide; however, large real-world datasets of patients with advanced gastric cancer are not well known.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>We investigated what differences exist in clinically relevant alterations for molecularly defined or age-stratified subgroups.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This was a collaborative biomarker study of a real-world dataset from comprehensive genomic profiling testing (Foundation Medicine, Inc.). Hybrid capture was carried out on at least 324 cancer-related genes and select introns from 31 genes frequently rearranged in cancer. Overall, 4634 patients were available for analyses and were stratified by age (≥ 40/&lt; 40 years), microsatellite instability status, tumor mutational burden status (high 10 ≥ /low &lt; 10 Muts/Mb), Epstein–Barr virus status, and select gene alterations. We analyzed the frequency of alterations with a chi-square test with Yate’s correction.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Genes with frequent alterations included <i>TP53</i> (60.1%), <i>ARID1A</i> (19.6%), <i>CDKN2A</i> (18.2%), <i>KRAS</i> (16.6%), and <i>CDH1</i> (15.8%). Differences in comprehensive genomic profiling were observed according to molecularly defined or age-stratified subgroups. Druggable genomic alterations were detected in 31.4% of patients; <i>ATM</i> (4.4%), <i>BRAF</i> V600E (0.4%), <i>BRCA1</i> (1.5%), <i>BRCA2</i> (2.9%), <i>ERBB2</i> amplification (9.2%), <i>IDH1</i> (0.2%), <i>KRAS</i> G12C (0.7%), microsatellite instability-high (4.8%), <i>NTRK1/2/3</i> fusion (0.13%), <i>PIK3CA</i> mutation (11.4%), and tumor mutational burden-high (9.4%). <i>CDH1</i> alterations and <i>MET</i> amplification were significantly more frequent in patients aged &lt; 40 years (27.7 and 6.2%) than in those aged ≥ 40 years (14.7 and 4.0%).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"15 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599051","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":"Efficacy of Regorafenib and Trifluridine/Tipiracil According to Extended RAS Evaluation in Advanced Metastatic Colorectal Cancer Patients: A Multicenter Retrospective Analysis","authors":"Michele Basso, Carlo Signorelli, Maria Alessandra Calegari, Jessica Lucchetti, Ina Valeria Zurlo, Emanuela Dell’Aquila, Giulia Arrivi, Federica Zoratto, Fiorenza Santamaria, Rosa Saltarelli, Giovanni Trovato, Giulia Caira, Lorenzo Angotti, Marta Schirripa, Annunziato Anghelone, Francesco Schietroma, Mario Giovanni Chilelli, Lisa Salvatore, Carmelo Pozzo, Giampaolo Tortora","doi":"10.1007/s11523-024-01050-3","DOIUrl":"https://doi.org/10.1007/s11523-024-01050-3","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Background&lt;/h3&gt;&lt;p&gt;There are few molecular markers driving treatment selection in later lines of treatment for advanced colorectal cancer patients. The vast majority of patients who progress after first- and second-line therapy undergo chemotherapy regardless of molecular data.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Objective&lt;/h3&gt;&lt;p&gt;We aimed to assess the prognostic and predictive effects of specific &lt;i&gt;RAS&lt;/i&gt; mutations on overall survival of patients receiving regorafenib (rego), trifluridine/tipiracil (TFD/TPI), or both.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Patients and methods&lt;/h3&gt;&lt;p&gt;This was a retrospective observational study based on data from a previous study of our research network, involving nine Italian institutions over a 10-year timeframe (2012–2022). Extended &lt;i&gt;RAS&lt;/i&gt; analysis, involving &lt;i&gt;KRAS&lt;/i&gt; exon 2–4 and &lt;i&gt;NRAS&lt;/i&gt; exon 2–4, and &lt;i&gt;BRAF&lt;/i&gt; were the main criteria for inclusion in this retrospective evaluation. Patients with &lt;i&gt;BRAF&lt;/i&gt; mutation were excluded. Patients were classified according to treatment (rego- or TFD/TPI-treated) and &lt;i&gt;RAS&lt;/i&gt; mutational status (wild-type [WT], &lt;i&gt;KRAS&lt;/i&gt; codon 12 mutations, &lt;i&gt;KRAS&lt;/i&gt; codon 13 mutations, &lt;i&gt;KRAS&lt;/i&gt; rare mutations and &lt;i&gt;NRAS&lt;/i&gt; mutations, &lt;i&gt;KRAS&lt;/i&gt; G12C mutation and &lt;i&gt;KRAS&lt;/i&gt; G12D mutation).&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;Overall, 582 patients were included in the present analysis. Overall survival did not significantly differ in rego-treated patients according to &lt;i&gt;RAS&lt;/i&gt; extended analysis, although a trend toward a better median survival in patients carrying G12D mutation (12.0 months), Codon 13 mutation (8.0 months), and Codon 12 mutation (7.0 months) has been observed, when compared with WT patients (6.0 months). Overall survival did not significantly differ in TFD/TPI-treated patients according to &lt;i&gt;RAS&lt;/i&gt; extended analysis, although a trend toward a better median survival in WT patients had been observed (9.0 months) in comparison with the entire population (7.0 months). Patients receiving both drugs displayed a longer survival when compared with the population of patients receiving rego alone (&lt;i&gt;p&lt;/i&gt; = 0.005) as well as the population receiving TFD/TPI alone (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), suggesting a group enriched for favorable prognostic factors. However, when each group was analyzed separately, the addition of TFD/TPI therapy to the rego-treated group improved survival only in all-RAS WT patients (&lt;i&gt;p&lt;/i&gt; = 0.003). Differently, the addition of rego therapy to TFD/TPI-treated patients significantly improved OS in the Codon 12 group (&lt;i&gt;p&lt;/i&gt; = 0.0004), G12D group (&lt;i&gt;p&lt;/i&gt; = 0.003), and the rare mutations group (&lt;i&gt;p&lt;/i&gt; = 0.02), in addition to all-RAS WT patients (&lt;i&gt;p&lt;/i&gt; = 0.002). The rego-TFD/TPI sequence, compared with the reverse sequence, significantly improved OS only in the &lt;i&gt;KRAS&lt;/i&gt; codon 12 group (&lt;i&gt;p&lt;/i&gt; = 0.003).&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusions&lt;/h3&gt;&lt;p&gt;","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"54 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599048","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":"Real-World Data on Subsequent Therapy for First-Line Osimertinib-Induced Pneumonitis: Safety of EGFR-TKI Rechallenge (Osi-risk Study TORG-TG2101)","authors":"Naoya Nishioka, Hisao Imai, Masahiro Endo, Akifumi Notsu, Kosei Doshita, Satoshi Igawa, Hiroshi Yokouchi, Takashi Ninomiya, Takaaki Tokito, Sayo Soda, Takasato Fujiwara, Tetsuhiko Asao, Shinji Nakamichi, Takahisa Kawamura, Minehiko Inomata, Kazuhisa Nakashima, Kentaro Ito, Yasuhiro Goto, Yukihiro Umeda, Soichi Hirai, Ryota Ushio, Keiki Yokoo, Takayuki Takeda, Tomoya Fukui, Masashi Ishihara, Takashi Osaki, Sousuke Kubo, Takumi Fujiwara, Chie Yamamoto, Takeshi Tsuda, Nobumasa Tamura, Shinobu Hosokawa, Yusuke Chihara, Satoshi Ikeda, Naoki Furuya, Yoshiro Nakahara, Satoru Miura, Hiroaki Okamoto","doi":"10.1007/s11523-024-01048-x","DOIUrl":"https://doi.org/10.1007/s11523-024-01048-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (<i>EGFR</i>) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis.</p><h3 data-test=\"abstract-sub-heading\">Patients and Methods</h3><p>We retrospectively reviewed the data of patients with <i>EGFR</i> mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17–39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3–7.5; <i>p</i> = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12–9.68;<i> p</i> = 0.03).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"72 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599047","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":"Frequency and Nature of Genomic Alterations in ERBB2-Altered Urothelial Bladder Cancer","authors":"","doi":"10.1007/s11523-024-01056-x","DOIUrl":"https://doi.org/10.1007/s11523-024-01056-x","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background</h3> <p>Human epidermal growth factor-2 (HER2) overexpression is an oncogenic driver in many solid tumors, including urothelial bladder cancer (UBC). In addition, activating mutations in the <em>ERBB2</em> gene have been shown to play an oncogenic role similar to <em>ERBB2</em> amplification.</p> </span> <span> <h3>Objective</h3> <p>To describe and compare the frequency and nature of genomic alterations (GA) of <em>ERBB2</em>-altered (mutations, amplification) and <em>ERBB2</em> wild-type UBC.</p> </span> <span> <h3>Patients and Methods</h3> <p>Using a hybrid capture-based comprehensive profiling assay, 9518 UBC cases were grouped by <em>ERBB2</em> alteration and evaluated for all classes of genomic alterations (GA), tumor mutational burden (TMB), microsatellite instability (MSI), genome-wide loss of heterozygosity (gLOH), and genomic mutational signature. PD-L1 expression was measured by immunohistochemistry (Dako 22C3). Categorical statistical comparisons were performed using Fisher’s exact tests.</p> </span> <span> <h3>Results</h3> <p>A total of 602 (6.3%) UBC cases featured <em>ERBB2</em> extracellular domain short variant (SV) GA (ECDmut+), 253 (2.7%) cases featured <em>ERBB2</em> kinase domain SV GA (KDmut+), 866 (9.1%) cases had <em>ERBB2</em> amplification (amp+), and 7797 (81.9%) cases were <em>ERBB2</em> wild-type (wt). European genetic ancestry of ECDmut+ was higher than <em>ERBB2</em>wt. Numerous significant associations were observed when comparing GA by group. Notably among these, <em>CDKN2A/MTAP</em> loss were more frequent in <em>ERBB2</em>wt versus ECDmut+ and amp+. <em>ERBB3</em> GA were more frequent in ECDmut+ and KDmut+ than <em>ERBB2</em>wt. <em>TERT</em> GA were more frequent in ECDmut+, KDmut+, and amp+ versus <em>ERBB2</em>wt. <em>TOP2A</em> amplification was significantly more common in ECDmut+ and amp+ versus <em>ERBB2</em>wt, and <em>TP53</em> SV GA were significantly higher in <em>ERBB2</em> amp+ versus <em>ERBB2</em>wt. Mean TMB levels were significantly higher in ECDmut+, KDmut+, and amp+ than in <em>ERBB2</em>wt. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptides (APOBEC) signature was more frequent in ECDmut+, KDmut+, and amp+ versus <em>ERBB2</em>wt. No significant differences were observed in PD-L1 status between groups, while gLOH-high status was more common in amp+ versus <em>ERBB2</em>wt. MSI-high status was more frequent in KDmut+ versus <em>ERBB2</em>wt, and in <em>ERBB2</em>wt than in amp+.</p> </span> <span> <h3>Conclusions</h3> <p>We noted important differences in co-occurring GA in <em>ERBB2</em>-altered (ECDmut+, KDmut+, amp+) versus <em>ERBB2</em>wt UBC, as well as higher mean TMB and higher APOBEC mutational signature in the <em>ERBB2</em>-altered groups. Our results can help refine future clinical trial designs and elucidate possible response and resistance mechanisms for <em>ERBB2</em>-altered UBC.</p> </span>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"14 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599045","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":"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}