Oncology and Therapy最新文献

{"title":"Palbociclib in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer: A Systematic Scoping Review of Real-World Evidence from Countries Outside of Western Regions that Are Underrepresented in Clinical Trials.","authors":"Amit Rauthan, Ankita Jain, Manmohan Singh, Mehmet A N Sendur","doi":"10.1007/s40487-024-00295-2","DOIUrl":"10.1007/s40487-024-00295-2","url":null,"abstract":"<p><strong>Introduction: </strong>Limited awareness exists regarding real-world data (RWD) for palbociclib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced/metastatic breast cancer in populations from certain countries outside of Western regions.</p><p><strong>Methods: </strong>A systematic scoping review was conducted using PubMed and Embase to evaluate RWD for palbociclib from countries outside of Western regions that are underrepresented in clinical trials. Search criteria were aligned with our research question for relevant English-language publications, without restrictions on publication date, followed by Phase 1 (title and abstract) and Phase 2 (full-text) screening of retrieved citations as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analyses of eligible studies were done separately for abstracts and full-text publications to enhance the precision and reliability of the results.</p><p><strong>Results: </strong>Database search yielded 1485 non-duplicate records, 46 qualified for inclusion, of which 47.8% were published as full text. The analysis of outcomes, based exclusively on full-text publications that collectively included 2048 patients treated with palbociclib, revealed the median progression-free survival (PFS) of 20.2-36.7 months, overall survival (OS) of 39.9 months (reported in one publication) and objective response rate (ORR) of 45.3-80.0% with first-line treatment. In ≥ second line, the median PFS, OS and ORR ranged from 7.0 to 24.2 months, 11 to 19.6 months, and 13.9% to 47.9%, respectively. The safety profile of palbociclib was similar to that reported in pivotal clinical studies, and no new safety concerns were identified.</p><p><strong>Conclusions: </strong>A comprehensive volume of evidence demonstrates that palbociclib's effectiveness and safety profile in real-world settings align with those observed in clinical trials, offering valuable insights for clinical decision-making in countries outside of Western regions underrepresented in clinical trials.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"395-418"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Patterns and Resource Use After Osimertinib Discontinuation in Patients with EGFR + Metastatic NSCLC.","authors":"Elizabeth Marrett, Winghan Jacqueline Kwong, Jinlin Song, Ameur Manceur, Selvam Sendhill, Eric Wu","doi":"10.1007/s40487-024-00292-5","DOIUrl":"10.1007/s40487-024-00292-5","url":null,"abstract":"<p><strong>Introduction: </strong>Current treatment guidelines for patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small cell lung cancer (mNSCLC) recommend EGFR tyrosine kinase inhibitors (TKIs) as the standard of care for first-line treatment, with third-generation osimertinib the preferred choice. However, most patients develop resistance to targeted therapy, and subsequent systemic chemotherapy is recommended. The aim of this study was to characterize the subsequent line of therapy (LOT) following osimertinib in patients with EGFR-mNSCLC.</p><p><strong>Methods: </strong>Medical and pharmacy claims of adults who initiated a subsequent LOT (index) after initial osimertinib discontinuation between November 2015 and September 2019 were analyzed retrospectively.</p><p><strong>Results: </strong>A total of 135 patients met the inclusion criteria. After metastatic diagnosis, 22.2% and 49.6% of patients were treated with osimertinib in the first and second line, respectively. After osimertinib discontinuation, most patients were treated with a platinum-based chemotherapy regimen (57%), of which 40.3% included immuno-oncology therapy. Reuse or continuation of EGFR TKIs was also common (24%). Overall, the median time to treatment discontinuation for the index LOT was 2.4 months. Proportions of patients with ≥ 1 inpatient or emergency department visit were 31.9% and 35.6%, respectively.</p><p><strong>Conclusions: </strong>The duration of the LOT following osimertinib was short and associated with tolerability issues underscoring a high unmet need for new therapies to address EGFR TKI resistance.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"549-563"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient Characteristics Associated with Time to Next Treatment in Patients with Ovarian Cancer Treated with Niraparib: The PRED1CT Real-World Study.","authors":"Dana M Chase, Soham Shukla, Julia Moore, Tirza Areli Calderón Boyle, Jonathan Lim, Jessica Perhanidis, Jean A Hurteau, Jeanne M Schilder","doi":"10.1007/s40487-024-00294-3","DOIUrl":"10.1007/s40487-024-00294-3","url":null,"abstract":"<p><strong>Introduction: </strong>Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy.</p><p><strong>Methods: </strong>This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Patients were followed until the earliest occurrence of last clinical activity, death, or end of study period. TTNT was measured from 1LM niraparib initiation to the start of second-line treatment or death. Cox proportional hazards models assessed univariable and multivariable associations between baseline characteristics and TTNT.</p><p><strong>Results: </strong>Of 7872 patients diagnosed with OC, 526 met the eligibility criteria and were included in this analysis. Median (IQR) duration of follow-up was 14.1 (7.4-23.6) months. In univariable analyses, age, BRCA/homologous recombination deficiency (HRD) status, socioeconomic status, stage at initial diagnosis, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT and were introduced into the multivariable model with other clinically relevant variables. In the multivariable analysis, BRCA/HRD status, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT after covariate adjustment. Conversely, age, Eastern Cooperative Oncology Group performance status, disease stage, niraparib starting dose status, and first-line bevacizumab use were not associated with observed TTNT.</p><p><strong>Conclusion: </strong>This real-world, retrospective, observational analysis offers valuable insights on prognostic factors associated with TTNT in patients with OC treated with 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Future studies are needed to examine how additional patient characteristics associated with clinical outcomes may guide treatment decisions and improve outcomes.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"599-607"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World First-Line Maintenance Niraparib Monotherapy Use Following Chemotherapy Plus Bevacizumab: The SW1TCH Study.","authors":"Bobbie Rimel, Tirza Areli Calderón Boyle, Sara Burns, Jonathan Lim, John Hartman, Linda Kalilani, Jeanne M Schilder, Jean A Hurteau, Amanda Golembesky","doi":"10.1007/s40487-024-00281-8","DOIUrl":"10.1007/s40487-024-00281-8","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab.</p><p><strong>Methods: </strong>This retrospective observational study used data from a US-based nationwide database of deidentified, electronic health record-derived data. Patients diagnosed with OC during the study period (1 January 2011-30 November 2022, inclusive) were eligible if they received 1L chemotherapy plus bevacizumab treatment followed by 1LM niraparib monotherapy, initiated between 1 January 2017 (inclusive) and 2 September 2022. Patients were followed from index date (initiation of niraparib 1LM) until the first occurrence of death, end of follow-up, or end of study. Clinical outcomes were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Kaplan-Meier curves were used to estimate TTD, TTNT, and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Among 93 patients selected, median age at index was 67 years (interquartile range [IQR] 60-72 years). Most patients had BRCA wild-type/homologous recombination (HR)-proficient or BRCA wild-type/HR unknown disease (75.3%). In all, 18 (19.4%) patients had HR-deficient disease. Five (5.4%) patients had unknown test results for both BRCA and HR deficiency status. Median follow-up time was 16.3 months (IQR 8.7-25.4 months), and median time from end of 1L therapy to 1LM initiation was 35.0 days (IQR 25.0-53.9 days). Median TTD was 9.3 months (95% CI 6.1-11.3 months). Median TTNT was 12.9 months (95% CI 11.5-19.0 months).</p><p><strong>Conclusions: </strong>This real-world study provided insights into switch maintenance with 1LM niraparib monotherapy, which may be a viable treatment option for patients with advanced OC.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"465-475"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Internal Psychometric Validation of an International Burden of Illness Survey for Idiopathic Multicentric Castleman Disease.","authors":"Matthew Franklin, Francis Shupo, Grace Wayi-Wayi, Natasa Zibelnik, Emily Jones, Nicola Mason, John Brazier, Sudipto Mukherjee","doi":"10.1007/s40487-024-00293-4","DOIUrl":"10.1007/s40487-024-00293-4","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic multicentric Castleman disease (iMCD) is a rare, chronic, debilitating lymphoproliferative disorder where the mainstay of treatment is symptom management. Our recent international patient survey showed that patients with iMCD have a high symptom burden that has a significant negative patient-reported impact on several aspects of daily life. As part of our ongoing work towards the development of an iMCD symptom burden scale, assessing the survey's psychometric properties is a critical step in understanding its adequacy, relevance, and usefulness. As iMCD is a rare disease, there are challenges to conducting such psychometric analyses which we describe.</p><p><strong>Methods: </strong>As part of the exploratory psychometric analysis, three a priori hypothesis sets (HS) were generated by interviewing an iMCD-experienced clinician, a patient, and a caregiver to explore the iMCD patient survey's internal construct validity, given no gold standard iMCD measure exists for external construct validation. HS-1 hypothesized that a convergent or discriminant relationship exists with the patients' self-assessment of symptom effect on daily life between two potentially related or unrelated symptoms, respectively. HS-2 hypothesized that having a greater number of symptoms has a positive convergent relationship with the patients' assessment of symptoms' effect on daily life. Finally, HS-3 hypothesized that patients receiving treatment versus no treatment was associated with patients reporting less effect of symptom burden on their daily life. Spearman's rank absolute correlation strength (ACS) was used for HS-1 and HS-2 (convergent relationship, ACS ≥ 0.3 and p value < 0.05; divergent relationship, ACS < 0.3), and Cohen's d to quantify standardized absolute effect sizes (AES) for HS-3 (AES ≥ 0.5 and p value < 0.05).</p><p><strong>Results: </strong>Our analyses partially supported HS-1. None of the three positive convergent relationships were supported. Of the six discriminant relationships, only dizziness with impaired cognitive function and tiredness with dizziness were supported. HS-2 analyses showed there was convergent validity between the number of symptoms and their effect on aspects of daily life. HS-3 analyses did not provide evidence to support the hypothesis.</p><p><strong>Conclusion: </strong>These internal psychometric construct analyses provide initial support for the bespoke iMCD patient survey and will guide additional work towards the development of the first iMCD-specific symptom burden scale.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"491-508"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Changes in Circulating Tumor Fraction as a Predictor of Real-World Clinical Outcomes in Solid Tumor Malignancy Patients Treated with Immunotherapy.","authors":"Ryan D Gentzler, John Guittar, Akash Mitra, Wade T Iams, Terri Driessen, Regina Schwind, Michelle M Stein, Kristiyana Kaneva, Seung Won Hyun, Yan Liu, Adam J Dugan, Cecile Rose T Vibat, Chithra Sangli, Jonathan Freaney, Zachary Rivers, Josephine L Feliciano, Christine Lo, Kate Sasser, Rotem Ben-Shachar, Halla Nimeiri, Jyoti D Patel, Aadel A Chaudhuri","doi":"10.1007/s40487-024-00287-2","DOIUrl":"10.1007/s40487-024-00287-2","url":null,"abstract":"<p><strong>Introduction: </strong>A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort.</p><p><strong>Methods: </strong>This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15-180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone.</p><p><strong>Results: </strong>The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02).</p><p><strong>Conclusions: </strong>xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"509-524"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Safety, Tolerability, and Immunogenicity of BP02 (Trastuzumab Biosimilar) Compared to EU- and US-Approved Trastuzumab in Healthy Adult Male Volunteers: A Phase 1, Randomized, Double-Blind Study.","authors":"Christian Schwabe, Chris Wynne, Dayaker Reddy Dyapa, Arpitkumar Prajapati, Disha Dadke","doi":"10.1007/s40487-024-00289-0","DOIUrl":"10.1007/s40487-024-00289-0","url":null,"abstract":"<p><strong>Introduction: </strong>This study evaluated the pharmacokinetic (PK) equivalence between BP02 (a proposed trastuzumab biosimilar) and the reference trastuzumab approved in the EU (EU-trastuzumab) and the US (US-trastuzumab).</p><p><strong>Methods: </strong>In this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78 days. Serum drug concentration-time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80-125% bioequivalence criteria.</p><p><strong>Results: </strong>Baseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration-time curve (AUC) from the time of dosing to infinity (AUC_0-inf), AUC from the time of dosing until the time of the last quantifiable concentration (AUC_0-t), and peak serum concentration of trastuzumab (C_max) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects-three in the US-trastuzumab group and one in the BP02 group-discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies.</p><p><strong>Conclusion: </strong>This study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab.</p><p><strong>Trial registration: </strong>ANZCTR number: ACTRN12621000573853.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"477-490"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Identification and Management of Patients with Rash on Apalutamide.","authors":"Alison J Birtle, Luigi Formisano, Vincent Descamps, Peter Weisenseel, Antoni Vilaseca","doi":"10.1007/s40487-024-00290-7","DOIUrl":"10.1007/s40487-024-00290-7","url":null,"abstract":"<p><p>Apalutamide is a selective androgen receptor signalling inhibitor that is used in the treatment of prostate cancer. Skin rash is one of the most common adverse events with apalutamide. Although the majority of rash events are grade 1 and 2, the appearance of skin rash during treatment can lead to dose reduction, a pause in treatment or even treatment discontinuation, especially if patients present late when the rash has become severe. This in turn can result in a significant delay or even a permanent discontinuation in the patient's treatment of prostate cancer. As apalutamide is a generally well tolerated and an effective treatment for many men with advanced prostate cancer, it is extremely important to make attempts to prevent skin problems or to manage them at the earliest stage possible. We therefore have developed practical guidance for the management of apalutamide-related rash, including an infographic with recommendations for rash management by grade. Central to this approach is patient education and awareness. Encouraging patients to proactively care for their skin from the start of treatment and informing them of the risk of rash with apalutamide therapy are essential. If the patient observes any skin changes, they should be advised to report it straight away to their cancer care team. Adopting this simple, proactive approach of patient education and increased vigilance from the care team is expected to lead to early identification of rash and subsequent intervention to allow for quicker resolution and enable patients to continue their cancer treatment with a drug that can delay disease progression and increase survival in patients with prostate cancer.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"609-620"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desensitization Strategies for Donor-Specific Antibodies in HLA-Mismatched Stem Cell Transplantation Recipients: What We Know and What We Do Not Know.","authors":"Yang Zhou, Yu-Lun Chen, Xi-Yi Huang, Ying-Jun Chang","doi":"10.1007/s40487-024-00283-6","DOIUrl":"10.1007/s40487-024-00283-6","url":null,"abstract":"<p><p>In human leukocyte antigen (HLA)-mismatched allogeneic stem cell transplantation settings, donor-specific anti-HLA antibodies (DSAs) can independently lead to graft failure, including both primary graft rejection and primary poor graft function. Although several strategies, such as plasma exchange, intravenous immunoglobulin, rituximab, and bortezomib, have been used for DSA desensitization, the effectiveness of desensitization and transplantation outcomes in some patients remain unsatisfactory. In this review, we summarized recent research on the prevalence of anti-HLA antibodies and the underlying mechanism of DSAs in the pathogenesis of graft failure. We mainly focused on desensitization strategies for DSAs, especially novel methods that are being investigated in the preclinical stage and those with promising outcomes after preliminary clinical application.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"375-394"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring a Novel Approach to Spare Classic Chemotherapy in HER2-Low, ER-Positive Breast Cancer Based on Trastuzumab Deruxtecan Combined with Endocrine Therapy.","authors":"Luca Scafuri, Carlo Buonerba, Vincenzo Di Lauro, Vincenzo Tortora, Marco Cascella, Luigi Liguori, Antonella Sciarra, Francesco Sabbatino, Anna Diana, Antonio Marra, Paolo Tarantino, Dario Trapani, Mario Giuliano, Grazia Arpino, Giuseppe Curigliano, Giuseppe Di Lorenzo","doi":"10.1007/s40487-024-00286-3","DOIUrl":"10.1007/s40487-024-00286-3","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy.</p><p><strong>Objective: </strong>This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer.</p><p><strong>Methods: </strong>We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects.</p><p><strong>Conclusions: </strong>This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"363-373"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}