Oncology and Therapy最新文献

{"title":"The Role of Oncology Nurses and Advanced Practice Providers in the Treatment of Patients With HRR-Deficient mCRPC Receiving Talazoparib Plus Enzalutamide: A Podcast.","authors":"Jennifer L E Lloyd, Julia Batten","doi":"10.1007/s40487-025-00376-w","DOIUrl":"10.1007/s40487-025-00376-w","url":null,"abstract":"<p><p>Homologous recombination repair (HRR) is a DNA repair pathway that helps maintain genomic stability. About one quarter of patients with metastatic castration-resistant prostate cancer (mCRPC) have alterations in HRR genes. For adult patients in the USA with mCRPC harboring HRR gene alterations, the combination of talazoparib plus enzalutamide is an approved treatment option. The objective of this podcast, featuring two nurse practitioners, is to provide information for oncology nurses and advanced practice providers (APPs) on the use of talazoparib plus enzalutamide and its practical implementation aspects in the clinic. We discuss the importance of testing for HRR gene alterations in mCRPC, appropriate dosing and administration, and our clinical experiences of adverse event monitoring and dose modifications as illustrative examples of the role of oncology nurses and APPs in the treatment of mCRPC with talazoparib plus enzalutamide. Podcast and Infographic are available for this article. Podcast Video (MP4 172565 KB).</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"861-870"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070790","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":"Opportunities and Approaches to Optimising Advanced Cholangiocarcinoma Outcomes in the Era of Targeted Therapies: A Narrative Review.","authors":"Teresa Macarulla, Cindy Neuzillet, Gerald W Prager, Lorenza Rimassa, John Bridgewater","doi":"10.1007/s40487-025-00370-2","DOIUrl":"10.1007/s40487-025-00370-2","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) represents a diverse group of malignancies. It is often identified at a late stage after the opportunity for curable resection has passed. An international educational meeting on CCA was held in Barcelona in September 2024. The meeting described the challenges with obtaining accurate epidemiological estimates for CCA because of misdiagnosis and marked regional differences, reflecting the prevalence of socioeconomic risk factors. Early-stage CCA is usually asymptomatic, and when symptoms appear, they are nonspecific. Diagnosis and treatment planning should involve a multidisciplinary team (MDT) from the outset. The European Society for Medical Oncology (ESMO) guidelines recommend molecular testing using next-generation sequencing when advanced disease is diagnosed. Biopsy sampling is technically challenging; if insufficient quality tissue is collected for molecular testing, liquid biopsy can be used. If the tumour is unresectable, the recommended first-line treatment is cisplatin + gemcitabine + durvalumab a programmed cell death ligand 1 [PD-L1] inhibitor or pembrolizumab a programmed cell death protein 1 [PD-1] inhibitor. The development of targeted therapies has led to these treatments being recommended as second- or third-line therapy for patients with actionable gene alterations, while 5-fluorouracil-based chemotherapy is recommended for those without. Robust data support the use of ivosidenib in patients with IDH1 mutations (phase 3), and phase 2 trials showed efficacy of pemigatinib and futibatinib for patients with FGFR2 gene fusions, trastuzumab deruxtecan and zanidatamab for patients with HER2 overexpression/amplification, and dabrafenib + trametinib for patients with BRAF^V600E mutations. It is hoped that wider dissemination of the content from this meeting will improve outcomes of patients with CCA by encouraging earlier referral, increasing the use of early molecular testing, an MDT approach, and maximising the use of targeted therapies. Continued efforts to raise awareness, implement education outreach opportunities, and involve patient advocacy groups are encouraged to improve CCA outcomes.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"939-962"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253183","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":"Sequential Fibroblast Growth Factor Receptor Inhibition in Intrahepatic Cholangiocarcinoma: Navigating an Evolving Landscape of Resistance and Opportunity-A Case Report and Current Opinion.","authors":"Hideki Sasanuma, Hironori Yamaguchi","doi":"10.1007/s40487-025-00371-1","DOIUrl":"10.1007/s40487-025-00371-1","url":null,"abstract":"<p><p>Fibroblast growth factor receptor (FGFR)2 rearrangements define a distinct molecular subset of intrahepatic cholangiocarcinoma (iCCA) with therapeutic potential using FGFR inhibitors. However, acquired resistance invariably limits long-term efficacy, posing a significant clinical challenge. Sequential targeting with different FGFR inhibitors is an emerging strategy, yet robust evidence, particularly for third-line and beyond, is scarce, and a consensus on optimal sequencing and patient selection remains unreached. Here, we report a case of FGFR2-rearranged iCCA where the patient achieved a radiographic partial response (PR) to tasurgratinib (a third-line FGFR inhibitor) following prior progression on pemigatinib and futibatinib. This case underscores the sustained dependency on the FGFR pathway and highlights the potential clinical utility of rationally sequenced FGFR-targeted therapy even after multiple lines of treatment. More broadly, this report serves as a basis for a current opinion on the evolving landscape of sequential FGFR inhibition in iCCA. We delve into the complexities of acquired resistance, dissect the arguments for and against prolonged FGFR pathway blockade, explore the impact of co-occurring genomic alterations, discuss the controversies, research priorities, and the urgent need for a balanced perspective to guide future clinical practice and trial design in this rapidly advancing but still uncertain field.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"1243-1253"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859712","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":"The Management of ER-Low, HER2-Negative Breast Cancer in the United Kingdom: A Survey of Current Clinical Practice.","authors":"Ka Chai Sit, Alison M Berner, Conor McCahill, Sarah Atkinson, Melissa M Phillips, Kathryn Hawkesford, Vasileios Angelis, Peter E Hall","doi":"10.1007/s40487-025-00388-6","DOIUrl":"10.1007/s40487-025-00388-6","url":null,"abstract":"<p><strong>Introduction: </strong>The optimal management of oestrogen receptor (ER)-low HER2-negative breast cancer (BC) is unclear. We surveyed current approaches of UK clinicians in ER-low BC, and also present outcomes of ER-low early BC at single centre.</p><p><strong>Methods: </strong>Survey: We conducted an anonymised online survey of clinicians treating BC in the UK between 6 May and 5 June 2024. Participants were presented with clinical scenarios of ER-low (Allred ER3/ER4) BC with multiple-choice and free-text questions. Clinical audit: Patients diagnosed with stage I-III, ER2-4 HER2-negative BC undergoing neoadjuvant treatment (chemotherapy vs. chemo-immunotherapy) from 1 January 2017 to 31 December 2023 were included. Clinical data was collected retrospectively at Barts Health NHS Trust, London, UK. The primary endpoint was pathological complete response (pCR).</p><p><strong>Results: </strong>Survey: Of 72 survey respondents, 40% recommended neoadjuvant chemo-immunotherapy for ER3 disease vs. 10% for ER4 disease; 57% recommended adjuvant endocrine therapy for ER3 disease, and 90% for ER4 disease. In the advanced setting 75% recommended chemo-immunotherapy for PD-L1-positive ER3 disease with 7% recommending CDK4/6 inhibitors. For PDL1-positive ER4 disease, these percentages were 32% and 51% respectively. In PDL1-negative disease, chemotherapy rates were 81% for ER3 and 36% for ER4 disease. Clinical audit: Sixty-six patients receiving neoadjuvant treatment were included, with 29 belonging to the ER2, 30 belonging to the ER3 and 7 belonging to the ER4 groups respectively; 33% received neoadjuvant chemo-immunotherapy. pCR rate was 61%, with no association with ER score for chemotherapy (p = 0.319) and chemo-immunotherapy (p = 0.603).</p><p><strong>Conclusions: </strong>There is marked variation in approach to ER-low in the UK. The audit data suggests treating ER-low BC as triple-negative BC.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"1143-1154"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281475","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 and Physician Perspectives on Multiple Myeloma Data Presented at ASCO and EHA 2025: A Podcast.","authors":"Jenny Ahlstrom, Luciano J Costa","doi":"10.1007/s40487-025-00389-5","DOIUrl":"10.1007/s40487-025-00389-5","url":null,"abstract":"<p><p>In this plain language podcast, highlights from the American Society of Clinical Oncology (ASCO) Annual Meeting 2025 are discussed, supplemented with additional reflections from the European Hematology Association (EHA) 2025 Congress. These insights come from the perspective of an expert patient and physician, both of whom have experience and expertise in the field of multiple myeloma (MM). This podcast is intended to broaden the reach of complex data on MM from these scientific meetings to a broader audience, including nonspecialists, helping enable better informed treatment decisions between patients and healthcare professionals. Four key topics are discussed, including emerging measurable residual disease (MRD)-driven strategies, novel immunotherapies, supportive care, and precision medicine approaches. MRD negativity is becoming a therapeutic goal and monitoring benchmark in the era of novel immunotherapies, helping patients with MM to achieve long-term disease control and remission. Supportive care, including access to patient organization information and support, is a critical component of modern MM care to maximize treatment benefit and quality of life for patients while limiting treatment toxicities. Finally, personalized treatment approaches and the use of artificial intelligence could re-shape outcomes for patients, including those with high-risk smoldering MM who would benefit from early intervention. As the treatment landscape continues to evolve in MM, so does the likelihood of long-term disease control and the potential for functional cure-a goal that was once a fantasy but is increasingly definable and measurable. A glossary of abbreviations and terms used in this podcast is provided in the appendix for reference.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"881-893"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349142","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":"Application and Progress of Antibody-Drug Conjugates (ADCs) in the Treatment of Metastatic Triple-Negative Breast Cancer.","authors":"Banghong Xie, Chao Chen, Haolin Cai, Lili Wang, Mulan Chen, Jian Liu, Fan Wu, Weiwei Huang","doi":"10.1007/s40487-025-00379-7","DOIUrl":"10.1007/s40487-025-00379-7","url":null,"abstract":"<p><p>Metastatic triple-negative breast cancer (TNBC) lacks actionable targets, and chemotherapy yields median progression-free survival (mPFS) of 4.6-9.7 months and median overall survival (mOS) of 12.6-26.3 months. Immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase (PARP) inhibitors only help subsets (objective response rate [ORR] of ~ 5% and ~ 12%, respectively). Antibody-drug conjugates (ADCs) have emerged as a leading therapeutic strategy: sacituzumab govitecan extended mPFS to 5.6 months (ASCENT trial), SKB264 to 6.7 months, and datopotamab deruxtecan achieved an ORR of 79%. In Human epidermal growth factor receptor 2 (HER2)-low TNBC, trastuzumab deruxtecan prolonged OS to 18.2 months, while disitamab vedotin and SHR-A1811 achieved ORRs of 26% and 60%, respectively. ADCs targeting Human epidermal growth factor receptor 3 (HER3)-, Nectin-4-, LIV-1- and folate receptor α (FRα) showed responses in 22%-54% of cases. Resistance can arise via antigen loss, endocytic defects, lysosomal failure, and efflux pumps. Bispecific ADCs, linker optimization, and combination regimens (ICI, PARPi) are under investigation. Future efforts will focus on targeting epidermal growth factor receptor (EGFR) and FRα and on developing multimodal immunovascular strategies to sustain clinical benefit.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"919-937"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065739","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":"Clinical Burden of Recurrent Disease in High-Risk Endometrial Cancer.","authors":"Kalé Kponee-Shovein, Vimalanand S Prabhu, Yan Song, Lei Chen, Mu Cheng, Yeran Li, Yezhou Sun, Annalise Hilts, Qi Hua, Jasmine Lichfield, Linda Duska","doi":"10.1007/s40487-025-00352-4","DOIUrl":"10.1007/s40487-025-00352-4","url":null,"abstract":"<p><strong>Introduction: </strong>Disease-free survival (DFS) is commonly a primary endpoint in clinical trials of investigational therapies for early stage and/or high-risk endometrial cancer and may be indicative of therapeutic benefit prior to maturity of overall survival (OS) data; however, its role as a predictor of OS in high-risk endometrial cancer is unknown. Therefore, this study estimates the individual-level correlation between DFS and OS and the association between recurrent disease and OS in patients with high-risk endometrial cancer receiving adjuvant chemotherapy.</p><p><strong>Methods: </strong>Medicare beneficiaries with high-risk endometrial cancer who underwent surgery followed by adjuvant chemotherapy were identified from Surveillance, Epidemiology, and End Results data (2007-2019). OS and DFS from adjuvant chemotherapy initiation were estimated by Kaplan-Meier (KM) analyses; correlation was evaluated using Kendall's τ rank correlation. Multivariable Cox models were used to compare OS between recurrent and nonrecurrent patients at three landmark points and over the follow-up period.</p><p><strong>Results: </strong>Among 771 patients, 250 (32.4%) experienced recurrence (median follow-up 3.6 years). Median OS was not reached (5-year OS 72.7%); median DFS was 7.9 years (5-year DFS 58.1%). A positive correlation between DFS and OS was observed [Kendall's τ = 0.83; 95% confidence interval (CI) 0.79‒0.86; p < 0.001]. Across landmark points, recurrent patients had 3.8-5.2-fold higher risk of mortality (all p < 0.001). During follow-up, patients with recurrence had a higher risk of mortality than those without (hazard ratio 7.9; 95% CI 5.7‒10.8; p < 0.001).</p><p><strong>Conclusions: </strong>The findings of this study suggest that DFS may be a useful surrogate for OS in high-risk endometrial cancer, though validation in trial-level meta-analyses is needed, and highlight the substantial burden associated with recurrent disease, as evidenced by the four-fold to eight-fold higher risk of mortality across comparative assessments of OS. Effective novel therapies are needed to reduce the considerable burden of disease recurrence in this population.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"1007-1021"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620763","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":"The Immuno-oncology-Induced Cytokine Release Syndrome Patient Diary: A Content-Valid, Patient-Reported Outcome Measure.","authors":"Edward Ted Wells, Laurence Lucats, Giovanni Abbadessa, James Turnbull, Joyce R Talavera, Sophie R Van Tomme, Paul Cordero, Benoit Arnould, Matthew Reaney, Catherine Coulouvrat","doi":"10.1007/s40487-025-00383-x","DOIUrl":"10.1007/s40487-025-00383-x","url":null,"abstract":"<p><strong>Introduction: </strong>Cytokine release syndrome (CRS) occurs when the immune system reacts excessively to infections or certain immunotherapies, leading to a systemic inflammatory response. The clinical presentation of CRS is highly variable, ranging from mild symptoms, such as fever and fatigue, to severe, life-threatening conditions. Currently, there is no standardized method for collecting patient-reported data on CRS experiences. This study aims to develop a novel patient-reported outcome measure (PROM) to capture patients' experience with CRS.</p><p><strong>Methods: </strong>A comprehensive, multistep evidence-generation process was employed, including several research steps: a literature review and analysis of Sanofi clinical trial adverse event data, semi-structured interviews with clinical experts, advisory board meetings with clinical trial investigators, concept elicitation interviews with patients who experienced CRS, a PROM development workshop, cognitive debriefing interviews with clinical trial investigators, and cognitive debriefing interviews with patients.</p><p><strong>Results: </strong>This review identified various CRS-related signs and symptoms from literature and anonymized safety data from clinical trials. Clinical experts validated the preliminary conceptual model (CM) and identified additional relevant symptoms. Patient interviews revealed further symptoms and impacts, leading to the development of the immuno-oncology (IO)-induced CRS patient diary. This PROM was refined through iterative feedback from clinical experts and patients, ensuring it effectively captures the incidence, severity, and impact of CRS symptoms.</p><p><strong>Conclusions: </strong>The \"IO-induced CRS patient diary\" can be considered a content-valid tool for capturing and monitoring the most important patient-reportable symptoms and impacts of CRS in IO clinical trials. This PROM can provide a standardized understanding of IO-induced CRS from the patient perspective, where to date this has been mainly clinically assessed using diverse assessments.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"1119-1141"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214057","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":"Sequencing of Radium-223 and Lutetium-177 Vipivotide Tetraxetan: Maximizing the Benefit of Systemic Targeted Radiation Therapy in Metastatic Castration-Resistant Prostate Cancer.","authors":"Samuel Mehr, Ralph Hauke","doi":"10.1007/s40487-025-00377-9","DOIUrl":"10.1007/s40487-025-00377-9","url":null,"abstract":"<p><strong>Introduction: </strong>The goals of treatment for metastatic castration-resistant prostate cancer are disease management, improving quality of life, and prolonging life. Although androgen-receptor blockade and chemotherapy can control the disease for several years in most patients, resistance to treatment and continued disease progression are inevitable. Radionuclides have emerged as important tools in the therapeutic arsenal against prostate cancer. Appropriate sequencing with existing standards of care is paramount to ensure that patients get the maximum clinical benefit from as many life-prolonging therapies as possible during the treatment journey.</p><p><strong>Methods: </strong>We review radionuclide therapy for men with metastatic castration-resistant prostate cancer and present a treatment algorithm used in our specialist center to provide optimal care.</p><p><strong>Results: </strong>The goal of the treatment algorithm employed in our specialist center is to provide optimal patient care by using and sequencing appropriate systemic radionuclide therapy. The first step is to determine the extent of disease and metastases to offer personalized treatment to extend survival. Appropriate treatment sequencing can allow men to receive the life-prolonging benefits of radium-223 immediately upon bone-only progression, while remaining eligible to benefit from chemotherapy and/or lutetium-177 vipivotide tetraxetan (¹⁷⁷Lu-PSMA) upon further disease progression. Importantly, although prostate-specific antigen (PSA) is frequently perceived as a marker for prostatic disease burden, survival benefits of radionuclide therapy may be independent of change in PSA.</p><p><strong>Conclusions: </strong>As the majority of men with metastatic castration-resistant prostate cancer first present with bone-only metastases, they may be treated initially with radium-223, while still remaining eligible to benefit from chemotherapy and ¹⁷⁷Lu-PSMA upon subsequent progression of skeletal metastatic disease and/or the emergence of lymph node or visceral metastases. Graphical abstract available for this article.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"963-976"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253169","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":"A Decade of Treating ALK-Rearranged Non-Small Cell Lung Cancer in a Lower Middle-Income Country: Changing Patterns and Improving Survival.","authors":"Ullas Batra, Mansi Sharma, Irfan Ahmad, Senthil Rajappa, Shrinidhi Nathany, Luca Cantini, Rashi Sachdeva, Vanshika Batra, Ritwika Choudhury, Bhumi Agarwal, Abhinav Dewan, Sabeena Choudhary, B P Amrith, L M Darlong, Kundan Singh Chufal, Preetha Umesh, Kratika Bhatia, Paulo Nunes Filho, Kamal S Saini, Anurag Mehta","doi":"10.1007/s40487-025-00390-y","DOIUrl":"10.1007/s40487-025-00390-y","url":null,"abstract":"<p><strong>Introduction: </strong>Data regarding the comparative efficacy of various generations of tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC) in lower middle-income countries (LMICs) is scarce.</p><p><strong>Methods: </strong>A comprehensive assessment of anaplastic lymphoma kinase (ALK)-directed TKIs and treatment sequences was done for 249 patients (145 male, 104 female) with advanced NSCLC at a referral cancer hospital in New Delhi, India. The primary endpoints were overall survival (OS); progression-free survival on 1st-line (PFS1) therapy, 2nd-line (PFS2) therapy, and PFS1 + 2. Multivariable Cox proportional hazards and joint frailty modelling were used for progression events and OS, respectively.</p><p><strong>Results: </strong>With a median follow-up of 48 months, median OS, PFS1, and PFS1 + 2 were 46.6 (95% CI 36.9-67.0), 18.2 (95% CI 14.5-26.8), and 33.1 months (95% CI 28.6-41.6), respectively. Third-generation TKIs significantly improved PFS and OS over 1st-generation TKIs, whether used 1st-line or later (HR PFS1 0.08, 95% CI 0.02-0.32, p < 0.001; HR OS 0.13, 95% CI 0.02-0.94, p = 0.043; HR PFS2 0.36, 95% CI 0.19-0.71, p = 0.003). Joint frailty modelling confirmed the correlation between repeated progression events and mortality (shared frailty parameter theta = 1.78, p < 0.001). Alectinib (HR 0.53, 95% CI 0.33-0.84, p = 0.007) and lorlatinib (HR 0.49, 95% CI 0.31-0.77, p = 0.002) reduced progression risk. Temporal trend analyses showed fewer treatment lines and significantly improved outcomes in patients with brain metastases with 3rd-generation TKIs.</p><p><strong>Conclusions: </strong>This relatively large LMIC real-world study shows similar outcomes to Western data, and improved survival and lower risk of intracranial progression with 2nd- and 3rd-generation ALK-directed TKIs.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"1169-1185"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313994","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}