Pub Date : 2024-12-01DOI: 10.1016/j.esmoop.2024.104002
J. Delahousse , A.D. Wagner , S. Borchmann , A.A. Adjei , J. Haanen , F. Burgers , A. Letsch , A. Quaas , S. Oertelt-Prigione , B.C. Özdemir , R.H.A. Verhoeven , O. Della Pasqua , A. Paci , O. Mir
Background
In addition to the effect of body weight, a patient’s sex can influence the pharmacokinetics (PK) of anticancer agents, and thereby their activity and safety. The magnitude and relevance of sex differences, however, are currently unclear.
Methods
We carried out a systematic review of published studies (clinical, n ≥ 10) on Food and Drug Administration (FDA)-approved (on 31 January 2022) anticancer drugs (excluding hormonal agents), aiming to identify significant PK differences between male and female patients. A difference of ≥20% on PK parameters (clearance or trough concentration) was considered significant. The methodological quality was assessed using the National Institutes of Health study quality assessment tool. This systematic review was conducted according to the PRISMA2020 guidelines and a previously published protocol, which was registered in the PROSPERO database (number 291008).
Results
Data on 99 anticancer agents (for a total of 1643 abstracts and European Medicines Agency/FDA documents) were screened. The final dataset included 112 articles and 8 European Medicines Agency/FDA documents. The median size of a study cohort was 445 patients (range: 12-6468 patients). Significant PK differences (>+20% in clearance or apparent clearance in women) were identified for 14 drugs, and potentially significant PK differences (due to conflicting reports) for another 8 drugs. None of the studies included sex-based summaries to assess whether the observed differences in PK may impact the efficacy or safety profile.
Conclusions
Significant sex differences in PK have been identified including commonly used drugs of different classes, such as 5-fluorouracil, doxorubicin, paclitaxel, regorafenib, atezolizumab, and temozolomide. The risk–benefit ratio for such anticancer drugs is likely to be improved by the development of sex-specific dosing strategies. Additional sex-based PK-pharmacodynamic analyses are recommended during dose optimisation and are to be conducted in line with the FDA Project Optimus guidance. They should be reported even if no association between the patients’ sex and the activity and/or toxicity of an anticancer drug has been identified.
{"title":"Sex differences in the pharmacokinetics of anticancer drugs: a systematic review","authors":"J. Delahousse , A.D. Wagner , S. Borchmann , A.A. Adjei , J. Haanen , F. Burgers , A. Letsch , A. Quaas , S. Oertelt-Prigione , B.C. Özdemir , R.H.A. Verhoeven , O. Della Pasqua , A. Paci , O. Mir","doi":"10.1016/j.esmoop.2024.104002","DOIUrl":"10.1016/j.esmoop.2024.104002","url":null,"abstract":"<div><h3>Background</h3><div>In addition to the effect of body weight, a patient’s sex can influence the pharmacokinetics (PK) of anticancer agents, and thereby their activity and safety. The magnitude and relevance of sex differences, however, are currently unclear.</div></div><div><h3>Methods</h3><div>We carried out a systematic review of published studies (clinical, <em>n</em> ≥ 10) on Food and Drug Administration (FDA)-approved (on 31 January 2022) anticancer drugs (excluding hormonal agents), aiming to identify significant PK differences between male and female patients. A difference of ≥20% on PK parameters (clearance or trough concentration) was considered significant. The methodological quality was assessed using the National Institutes of Health study quality assessment tool. This systematic review was conducted according to the PRISMA2020 guidelines and a previously published protocol, which was registered in the PROSPERO database (number 291008).</div></div><div><h3>Results</h3><div>Data on 99 anticancer agents (for a total of 1643 abstracts and European Medicines Agency/FDA documents) were screened. The final dataset included 112 articles and 8 European Medicines Agency/FDA documents. The median size of a study cohort was 445 patients (range: 12-6468 patients). Significant PK differences (>+20% in clearance or apparent clearance in women) were identified for 14 drugs, and potentially significant PK differences (due to conflicting reports) for another 8 drugs. None of the studies included sex-based summaries to assess whether the observed differences in PK may impact the efficacy or safety profile.</div></div><div><h3>Conclusions</h3><div>Significant sex differences in PK have been identified including commonly used drugs of different classes, such as 5-fluorouracil, doxorubicin, paclitaxel, regorafenib, atezolizumab, and temozolomide. The risk–benefit ratio for such anticancer drugs is likely to be improved by the development of sex-specific dosing strategies. Additional sex-based PK-pharmacodynamic analyses are recommended during dose optimisation and are to be conducted in line with the FDA Project Optimus guidance. They should be reported even if no association between the patients’ sex and the activity and/or toxicity of an anticancer drug has been identified.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 104002"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.esmoop.2024.103996
S.-H. Lee , J. Menis , T.M. Kim , H.R. Kim , C. Zhou , S.A. Kurniawati , K. Prabhash , H. Hayashi , D.D.-W. Lee , M.S. Imasa , Y.L. Teh , J.C.-H. Yang , T. Reungwetwattana , V. Sriuranpong , C.-E. Wu , Y. Ang , M. Sabando , M. Thiagarajan , H. Mizugaki , V. Noronha , S. Popat
The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer (mNSCLC), published in January 2023, was modified according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with oncogene-addicted mNSCLC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with oncogene-addicted mNSCLC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Korean Society for Medical Oncology (KSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with oncogene-addicted mNSCLC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, while respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies between the different regions of Asia.
{"title":"Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer","authors":"S.-H. Lee , J. Menis , T.M. Kim , H.R. Kim , C. Zhou , S.A. Kurniawati , K. Prabhash , H. Hayashi , D.D.-W. Lee , M.S. Imasa , Y.L. Teh , J.C.-H. Yang , T. Reungwetwattana , V. Sriuranpong , C.-E. Wu , Y. Ang , M. Sabando , M. Thiagarajan , H. Mizugaki , V. Noronha , S. Popat","doi":"10.1016/j.esmoop.2024.103996","DOIUrl":"10.1016/j.esmoop.2024.103996","url":null,"abstract":"<div><div>The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer (mNSCLC), published in January 2023, was modified according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with oncogene-addicted mNSCLC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with oncogene-addicted mNSCLC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Korean Society for Medical Oncology (KSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with oncogene-addicted mNSCLC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, while respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies between the different regions of Asia.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103996"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.esmoop.2024.103992
L. Richter , S. Pauge , K. Mehlis , A. Zueger , B. Surmann , V. Mathies , W. Greiner , T. Ernst , E.C. Winkler , N. Menold
Background
Cancer diagnosis and therapy can lead to significant financial distress for those affected, even in universal health care systems. We present the development and validation of a patient-reported outcome measure for financial distress in German cancer patients.
Methods
Validation of the newly developed instrument followed a two-step approach, including two quantitative paper–pencil surveys (N1 = 111, N2 = 267) with patients of all types of cancer and treatment status at two German university hospitals. Factorial validity, reliability, construct, and criterion validity were assessed using exploratory and confirmatory factor analysis, correlative and linear regression analysis.
Results
The Financial Distress of Cancer Assessment Tool (FIAT) comprises 19 items across three domains of subjective financial distress: (i) financial worries; (ii) dissatisfaction across various life domains, and (iii) challenging experiences with authorities and benefit providers (e.g. employment agency, health insurance). Confirmatory factor analysis confirmed the instrument’s factorial structure. Composite reliability (Raykov’s rho) ranges from 0.88 to 0.96, and retest reliability ranges from 0.64 to 0.75. Correlational analyses showed significant associations between FIAT scores and related constructs [e.g. correlations with the EORTC-QLQ-C30 financial distress subscale (Q28) ranging from 0.47 to 0.60], supporting its construct validity. Additionally, higher FIAT scores were significantly associated with lower health-related quality of life measured by Q29 and Q30 of the EORTC-QLQ-C30, with correlations ranging from −0.21 to −0.28. They were also positively correlated with depression (PHQ-4), with correlations ranging from 0.33 to 0.45, and anxiety (PHQ-4) with correlations ranging from 0.25 to 0.36, confirming its criterion validity.
Conclusions
The newly developed patient-reported outcome measure is the first reported measurement tool to assess financial distress in German cancer patients. The instrument can be used for research purposes and to enable the provision of coordinated support services.
{"title":"Measuring financial distress in German cancer patients: development and validation of the Financial Distress of Cancer Assessment Tool (FIAT)","authors":"L. Richter , S. Pauge , K. Mehlis , A. Zueger , B. Surmann , V. Mathies , W. Greiner , T. Ernst , E.C. Winkler , N. Menold","doi":"10.1016/j.esmoop.2024.103992","DOIUrl":"10.1016/j.esmoop.2024.103992","url":null,"abstract":"<div><h3>Background</h3><div>Cancer diagnosis and therapy can lead to significant financial distress for those affected, even in universal health care systems. We present the development and validation of a patient-reported outcome measure for financial distress in German cancer patients.</div></div><div><h3>Methods</h3><div>Validation of the newly developed instrument followed a two-step approach, including two quantitative paper–pencil surveys (<em>N1</em> = 111, <em>N2</em> = 267) with patients of all types of cancer and treatment status at two German university hospitals. Factorial validity, reliability, construct, and criterion validity were assessed using exploratory and confirmatory factor analysis, correlative and linear regression analysis.</div></div><div><h3>Results</h3><div>The Financial Distress of Cancer Assessment Tool (FIAT) comprises 19 items across three domains of subjective financial distress: (i) financial worries; (ii) dissatisfaction across various life domains, and (iii) challenging experiences with authorities and benefit providers (e.g. employment agency, health insurance). Confirmatory factor analysis confirmed the instrument’s factorial structure. Composite reliability (Raykov’s rho) ranges from 0.88 to 0.96, and retest reliability ranges from 0.64 to 0.75. Correlational analyses showed significant associations between FIAT scores and related constructs [e.g. correlations with the EORTC-QLQ-C30 financial distress subscale (Q28) ranging from 0.47 to 0.60], supporting its construct validity. Additionally, higher FIAT scores were significantly associated with lower health-related quality of life measured by Q29 and Q30 of the EORTC-QLQ-C30, with correlations ranging from −0.21 to −0.28. They were also positively correlated with depression (PHQ-4), with correlations ranging from 0.33 to 0.45, and anxiety (PHQ-4) with correlations ranging from 0.25 to 0.36, confirming its criterion validity.</div></div><div><h3>Conclusions</h3><div>The newly developed patient-reported outcome measure is the first reported measurement tool to assess financial distress in German cancer patients. The instrument can be used for research purposes and to enable the provision of coordinated support services.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103992"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.esmoop.2024.103993
S. Schönecker , L. Angelini , A. Gaasch , A. Zinn , D. Konnerth , C. Heinz , Y. Xiong , K. Unger , G. Landry , I. Meattini , M. Braun , M. Pölcher , N. Harbeck , R. Würstlein , M. Niyazi , C. Belka , M. Pazos , S. Corradini
Background
Adjuvant radiotherapy (RT) plays an essential role in the management of early breast cancer (BC), but can lead to cardiovascular and lung toxicities. RT in deep inspiration breath hold (DIBH) often allows better protection of organs at risk. This prospective study compares surface-guided DIBH with free breathing (FB) in patients with left-sided BC, by evaluating individual cardiovascular risks and treatment plan dosimetry.
Patients and methods
The study enrolled 585 patients from October 2016 to January 2021 with left-sided invasive breast carcinoma with indicated adjuvant RT of the breast/thoracic wall with or without regional lymph nodes. The ability to hold breath for 20 s was a prerequisite. The treatments were either hypofractionated (HF; 40.05 Gy/15Fx) or normofractionated (NF; 50.00 Gy/25Fx). DIBH was applied using the automatically triggered surface guidance system Catalyst with audio–video feedback. Computed tomography and surface data were acquired during both DIBH and FB. The primary endpoint of the study was the comparative evaluation of heart dose reduction using DIBH.
Results
Plan dosimetry was significantly improved by DIBH. The mean and maximum doses to the heart and the left coronary artery were significantly reduced by 36%-42% in HF and NF plans (P < 0.001), while the mean ipsilateral lung dose was reduced by 12%-14% (P < 0.001). Furthermore, DIBH resulted in a 5% reduction in the cumulative 10-year cardiovascular disease risk (10-year cardiovascular disease risk) compared with FB (3.59% to 3.41%; P < 0.001).
Conclusion
To the best of our knowledge, this is the largest prospective study showing better sparing for cardiac and ipsilateral lung doses with surface-guided DIBH compared with FB in patients with left-sided BC.
{"title":"Surface-based deep inspiration breath-hold radiotherapy in left-sided breast cancer: final results from the SAVE-HEART study","authors":"S. Schönecker , L. Angelini , A. Gaasch , A. Zinn , D. Konnerth , C. Heinz , Y. Xiong , K. Unger , G. Landry , I. Meattini , M. Braun , M. Pölcher , N. Harbeck , R. Würstlein , M. Niyazi , C. Belka , M. Pazos , S. Corradini","doi":"10.1016/j.esmoop.2024.103993","DOIUrl":"10.1016/j.esmoop.2024.103993","url":null,"abstract":"<div><h3>Background</h3><div>Adjuvant radiotherapy (RT) plays an essential role in the management of early breast cancer (BC), but can lead to cardiovascular and lung toxicities. RT in deep inspiration breath hold (DIBH) often allows better protection of organs at risk. This prospective study compares surface-guided DIBH with free breathing (FB) in patients with left-sided BC, by evaluating individual cardiovascular risks and treatment plan dosimetry.</div></div><div><h3>Patients and methods</h3><div>The study enrolled 585 patients from October 2016 to January 2021 with left-sided invasive breast carcinoma with indicated adjuvant RT of the breast/thoracic wall with or without regional lymph nodes. The ability to hold breath for 20 s was a prerequisite. The treatments were either hypofractionated (HF; 40.05 Gy/15Fx) or normofractionated (NF; 50.00 Gy/25Fx). DIBH was applied using the automatically triggered surface guidance system Catalyst with audio–video feedback. Computed tomography and surface data were acquired during both DIBH and FB. The primary endpoint of the study was the comparative evaluation of heart dose reduction using DIBH.</div></div><div><h3>Results</h3><div>Plan dosimetry was significantly improved by DIBH. The mean and maximum doses to the heart and the left coronary artery were significantly reduced by 36%-42% in HF and NF plans (<em>P</em> < 0.001), while the mean ipsilateral lung dose was reduced by 12%-14% (<em>P</em> < 0.001). Furthermore, DIBH resulted in a 5% reduction in the cumulative 10-year cardiovascular disease risk (10-year cardiovascular disease risk) compared with FB (3.59% to 3.41%; <em>P</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>To the best of our knowledge, this is the largest prospective study showing better sparing for cardiac and ipsilateral lung doses with surface-guided DIBH compared with FB in patients with left-sided BC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103993"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.esmoop.2024.103997
K. Fanucci , A. Giordano , T. Erick , S.M. Tolaney , S. Sammons
Mutations in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway occur in 30%-40% of patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2−) breast cancer. For most patients, endocrine therapy with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor is the first-line treatment. Recent studies indicate that adding inavolisib, a PI3Kα inhibitor, to palbociclib/fulvestrant benefits patients with endocrine-resistant HR+/HER2− metastatic breast cancer with a PIK3CA mutation. Alpelisib and capivasertib are both US Food and Drug Administration (FDA) approved in combination with fulvestrant in patients with endocrine-resistant HR+/HER2−, PIK3CA-mutant metastatic breast cancer, both with activity in the post-CDK4/6 setting. Capivasertib added to fulvestrant is the first AKT inhibitor to show a significant progression-free survival benefit with a trend for overall survival benefit and the only approved option for patients with phosphate and tensin homolog (PTEN) or AKT alterations. Toxicity profiles of all agents necessitate careful patient selection. Several mutant-selective and pan-mutant-selective novel inhibitors are under investigation with the potential to improve tolerability and efficacy.
{"title":"Practical treatment strategies and novel therapies in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2−) advanced breast cancer","authors":"K. Fanucci , A. Giordano , T. Erick , S.M. Tolaney , S. Sammons","doi":"10.1016/j.esmoop.2024.103997","DOIUrl":"10.1016/j.esmoop.2024.103997","url":null,"abstract":"<div><div>Mutations in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway occur in 30%-40% of patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2−) breast cancer. For most patients, endocrine therapy with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor is the first-line treatment. Recent studies indicate that adding inavolisib, a PI3Kα inhibitor, to palbociclib/fulvestrant benefits patients with endocrine-resistant HR+/HER2− metastatic breast cancer with a <em>PIK3CA</em> mutation. Alpelisib and capivasertib are both US Food and Drug Administration (FDA) approved in combination with fulvestrant in patients with endocrine-resistant HR+/HER2−, <em>PIK3CA</em>-mutant metastatic breast cancer, both with activity in the post-CDK4/6 setting. Capivasertib added to fulvestrant is the first AKT inhibitor to show a significant progression-free survival benefit with a trend for overall survival benefit and the only approved option for patients with phosphate and tensin homolog (PTEN) or AKT alterations. Toxicity profiles of all agents necessitate careful patient selection. Several mutant-selective and pan-mutant-selective novel inhibitors are under investigation with the potential to improve tolerability and efficacy.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103997"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.esmoop.2024.104083
H. Jourdain , A. Di Meglio , I. Mansouri , D. Desplas , M. Zureik , N. Haddy
Background
Since 2020, trastuzumab deruxtecan (T-DXd) has been used in France for patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive or HER2-low metastatic breast cancer (mBC). We aimed to describe the clinical characteristics, outcomes, and potential toxicities among patients receiving T-DXd for HER2-positive and HER2-low mBC.
Patients and methods
Using the French National Health Data System (SNDS), we identified patients who initiated T-DXd for mBC from 30 September 2020 to 30 September 2023. Follow-up data were available through 31 December 2023. Patients were categorized into three groups according to HER2 expression and line of treatment: HER2-positive mBC receiving T-DXd in the third (HER2+ 3L) or second line (HER2+ 2L) and HER2-low mBC receiving T-DXd in the second line (HER2-low2L). We describe their characteristics and report the Kaplan–Meier estimates of overall survival (OS) and incidence of hospitalization.
Results
The cohort comprised 5890 patients, including 2010 (34.1%) HER2+ 3L, 1260 (21.4%) HER2+ 2L, and 2620 (44.5%) HER2-low2L. For the three respective groups, the median age at inclusion was 59 years [interquartile range (IQR) 51-69 years], 59 years (50-68 years), and 61 years (52-70 years); 34.8%, 30.2%, and 16.0% had brain metastases; 14.2%, 13.7%, and 13.4% had a current or history of cardiovascular disease. Median OS was 30.2 months [95% confidence interval (CI) 28.1-33.5 months] for HER2+ 3L patients, was not reached for HER2+ 2L patients, and was 16.8 months (95% CI 14.5 months-not reached) for HER2-low2L patients. The incidence of hospitalization for cardiac, respiratory, digestive, and hematological disorders was similar for HER2-positive patients treated in the second or third line, whereas HER2-low patients had higher incidence rates for these events.
Conclusion
In this large French observational study, T-DXd users were older, had more comorbidities, and had more brain metastases than patients included in registration trials. The rapid expansion of clinical indications of T-DXd calls for proactive surveillance and timely management of potentially life-threatening T-DXd-related toxicity.
{"title":"Use and outcomes of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer in a real-world setting: a nationwide cohort study","authors":"H. Jourdain , A. Di Meglio , I. Mansouri , D. Desplas , M. Zureik , N. Haddy","doi":"10.1016/j.esmoop.2024.104083","DOIUrl":"10.1016/j.esmoop.2024.104083","url":null,"abstract":"<div><h3>Background</h3><div>Since 2020, trastuzumab deruxtecan (T-DXd) has been used in France for patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive or HER2-low metastatic breast cancer (mBC). We aimed to describe the clinical characteristics, outcomes, and potential toxicities among patients receiving T-DXd for HER2-positive and HER2-low mBC.</div></div><div><h3>Patients and methods</h3><div>Using the French National Health Data System (SNDS), we identified patients who initiated T-DXd for mBC from 30 September 2020 to 30 September 2023. Follow-up data were available through 31 December 2023. Patients were categorized into three groups according to HER2 expression and line of treatment: HER2-positive mBC receiving T-DXd in the third (HER2+ 3L) or second line (HER2+ 2L) and HER2-low mBC receiving T-DXd in the second line (HER2-low2L). We describe their characteristics and report the Kaplan–Meier estimates of overall survival (OS) and incidence of hospitalization.</div></div><div><h3>Results</h3><div>The cohort comprised 5890 patients, including 2010 (34.1%) HER2+ 3L, 1260 (21.4%) HER2+ 2L, and 2620 (44.5%) HER2-low2L. For the three respective groups, the median age at inclusion was 59 years [interquartile range (IQR) 51-69 years], 59 years (50-68 years), and 61 years (52-70 years); 34.8%, 30.2%, and 16.0% had brain metastases; 14.2%, 13.7%, and 13.4% had a current or history of cardiovascular disease. Median OS was 30.2 months [95% confidence interval (CI) 28.1-33.5 months] for HER2+ 3L patients, was not reached for HER2+ 2L patients, and was 16.8 months (95% CI 14.5 months-not reached) for HER2-low2L patients. The incidence of hospitalization for cardiac, respiratory, digestive, and hematological disorders was similar for HER2-positive patients treated in the second or third line, whereas HER2-low patients had higher incidence rates for these events.</div></div><div><h3>Conclusion</h3><div>In this large French observational study, T-DXd users were older, had more comorbidities, and had more brain metastases than patients included in registration trials. The rapid expansion of clinical indications of T-DXd calls for proactive surveillance and timely management of potentially life-threatening T-DXd-related toxicity.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 104083"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27DOI: 10.1016/j.esmoop.2024.103989
F. Schettini , F. Brasó-Maristany , T. Pascual , N. Lorman-Carbó , S. Nucera , M. Bergamino , P. Galván , B. Conte , E. Seguí , I. García Fructuoso , R. Gómez Bravo , A.B. Rodríguez , O. Martínez-Sáez , N. Chic , M. Vidal , B. Adamo , B. González-Farre , E. Sanfeliu , I. Cebrecos , E. Mensión , A. Prat
Background
Predictors of response to neoadjuvant chemotherapy (NACT) and endocrine therapy (NET) in hormone receptor-positive (HoR+)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) are required. Also, pathological and molecular changes induced by both strategies and their impact on patients’ outcomes have not been reported so far.
Patients and methods
In a cohort of 186 patients with early-stage HoR+/HER2-negative BC treated with NACT or NET, we assessed the association of baseline main clinicopathological features and PAM50 gene expression (GE), intrinsic subtypes (IS) and risk-of-relapse (ROR-P) score with pathological outcomes according to treatment strategy. Molecular NACT/NET-induced changes were described and compared, along with their associations with event-free survival (EFS). Comparison of the two cohorts after propensity score matching (PSM) was used as sensitivity analysis. Molecular changes were confirmed in cell lines.
Results
NACT was associated with higher rates of residual cancer burden (RCB)-0/I than NET in the overall population (38.2% versus 13.5%, P < 0.001) and after PSM (P = 0.036). PAM50 non-luminal IS were the only independent and positive predictor of RCB-0/I (P = 0.024) in the NACT cohort, while MMP11 messenger RNA levels were the only independent and negative predictor (P = 0.014) in the NET cohort. Both treatments shifted the tumor types toward less aggressive forms (i.e. PAM50 luminal A/normal-like), lowered the risk of recurrence in terms of ROR-P, up-regulated selected immune genes and PAM50 basal-like-related genes/signature and significantly downregulated proliferation-/luminal-/HER2-related genes/signatures, though NACT more than NET. Molecular findings were confirmed after PSM. A net reduction in proliferation-related genes and ROR-P was confirmed in cell lines with chemotherapy and endocrine therapy. Different baseline molecular features associated with diverse kind of responses (ROR-P downstaging, Ki67 reduction or pathological responses) with NACT and NET. Decreasing ROR-P and transitioning the tumor subtype to resemble normal tissue (i.e. PAM50 normal-like) suggested improved EFS.
Conclusions
NACT was more effective in the molecular and dimensional tumor ‘downstaging’ than NET but baseline molecular features associated with differential responses according to treatment strategy. Examining baseline and post-treatment GE might help tailor more personalized and effective care.
{"title":"Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study☆","authors":"F. Schettini , F. Brasó-Maristany , T. Pascual , N. Lorman-Carbó , S. Nucera , M. Bergamino , P. Galván , B. Conte , E. Seguí , I. García Fructuoso , R. Gómez Bravo , A.B. Rodríguez , O. Martínez-Sáez , N. Chic , M. Vidal , B. Adamo , B. González-Farre , E. Sanfeliu , I. Cebrecos , E. Mensión , A. Prat","doi":"10.1016/j.esmoop.2024.103989","DOIUrl":"10.1016/j.esmoop.2024.103989","url":null,"abstract":"<div><h3>Background</h3><div>Predictors of response to neoadjuvant chemotherapy (NACT) and endocrine therapy (NET) in hormone receptor-positive (HoR+)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) are required. Also, pathological and molecular changes induced by both strategies and their impact on patients’ outcomes have not been reported so far.</div></div><div><h3>Patients and methods</h3><div>In a cohort of 186 patients with early-stage HoR+/HER2-negative BC treated with NACT or NET, we assessed the association of baseline main clinicopathological features and PAM50 gene expression (GE), intrinsic subtypes (IS) and risk-of-relapse (ROR-P) score with pathological outcomes according to treatment strategy. Molecular NACT/NET-induced changes were described and compared, along with their associations with event-free survival (EFS). Comparison of the two cohorts after propensity score matching (PSM) was used as sensitivity analysis. Molecular changes were confirmed in cell lines.</div></div><div><h3>Results</h3><div>NACT was associated with higher rates of residual cancer burden (RCB)-0/I than NET in the overall population (38.2% versus 13.5%, <em>P</em> < 0.001) and after PSM (<em>P</em> = 0.036). PAM50 non-luminal IS were the only independent and positive predictor of RCB-0/I (<em>P</em> = 0.024) in the NACT cohort, while <em>MMP11</em> messenger RNA levels were the only independent and negative predictor (<em>P</em> = 0.014) in the NET cohort. Both treatments shifted the tumor types toward less aggressive forms (i.e. PAM50 luminal A/normal-like), lowered the risk of recurrence in terms of ROR-P, up-regulated selected immune genes and PAM50 basal-like-related genes/signature and significantly downregulated proliferation-/luminal-/HER2-related genes/signatures, though NACT more than NET. Molecular findings were confirmed after PSM. A net reduction in proliferation-related genes and ROR-P was confirmed in cell lines with chemotherapy and endocrine therapy. Different baseline molecular features associated with diverse kind of responses (ROR-P downstaging, Ki67 reduction or pathological responses) with NACT and NET. Decreasing ROR-P and transitioning the tumor subtype to resemble normal tissue (i.e. PAM50 normal-like) suggested improved EFS.</div></div><div><h3>Conclusions</h3><div>NACT was more effective in the molecular and dimensional tumor ‘downstaging’ than NET but baseline molecular features associated with differential responses according to treatment strategy. Examining baseline and post-treatment GE might help tailor more personalized and effective care.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103989"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27DOI: 10.1016/j.esmoop.2024.103986
P. García-Alfonso , E. Elez , J. Soto-Alsar , D. Páez , A. Fernández-Montes , B. Graña , A. Salud , A. Yubero , M.A. Gómez-España , I. Macías , G. Quintero , C. López-López , T. Fernández-Rodríguez , C. Grávalos , E. González-Flores , M. Guix , B. García Paredes , J.J. Reina , J.R. Rodríguez Mowbray , J. Sastre , E. Aranda
Background
The combination chemotherapy i.v. 5-fluorouracil (5-FU), irinotecan, and aflibercept (FOLFIRI-A) is a standard second-line treatment of metastatic colorectal cancer (mCRC). The aim was to assess maintenance treatment in second-line setting in older patients (aged ≥70 years) with mCRC.
Patients and methods
We evaluated FOLFIRI-A given for six cycles followed by maintenance with 5-FU/leucovorin (LV)-A (arm A) or FOLFIRI-A (arm B) until progression in older adults with mCRC in the AFEMA randomized, open-label, non-inferiority phase II trial (EudraCT2016-004076-21/NCT03279289). Patients aged ≥70 years who previously failed oxaliplatin-fluoropyrimidine were randomly allocated (1 : 1) to either arm A (experimental) or arm B (control). After enrolling 35 patients, the FOLFIRI dose was reduced to level 1 in both arms due to toxicity. The primary endpoint was median progression-free survival (PFS); and secondary endpoints were median overall survival, objective response rate, and safety. Non-inferiority required the upper confidence interval (CI) limit to not exceed a hazard ratio (HR) of 1.5 (one-sided α = 0.075, 80% power).
Results
A total of 170 patients were randomly allocated to arm A or arm B (n = 85 each). The median follow-up was 12.2 versus 10.9 months in arm A versus arm B. Most patients died (83.5% versus 88.2% in arm A versus arm B), mainly from disease progression. PFS non-inferiority was met (HR = 0.78, 95% CI 0.566-1.076, P = 0.131) with a median PFS of 6.1 versus 5.5 months in arm A versus arm B. Median overall survival was similar in arms A and B (12.2 and 11.5 months, respectively) (HR = 0.89, 95% CI 0.640-1.227, P = 0.467). During the maintenance phase, severe asthenia (4.5% versus 21.6%, P = 0.038), serious adverse events (SAEs) (17.8% versus 37.8%, P = 0.049), and treatment-related SAEs (6.7% versus 10.8%, P = 0.695) were reduced in arm A versus arm B.
Conclusion
In older adults, induction with six cycles of FOLFIRI-A plus maintenance with 5-FU/LV-A was non-inferior to FOLFIRI-A until progression. Severe asthenia, SAEs, and treatment-related SAEs were reduced with 5-FU/LV-A maintenance.
背景静脉注射5-氟尿嘧啶（5-FU）、伊立替康和阿弗利百普（FOLFIRI-A）联合化疗是转移性结直肠癌（mCRC）的标准二线治疗方法。患者和方法我们在AFEMA随机、开放标签、非劣效II期试验（EudraCT2016-004076-21/NCT03279289）中评估了老年mCRC患者在给予FOLFIRI-A治疗6个周期后使用5-FU/亮菌甲素（LV）-A（A组）或FOLFIRI-A（B组）维持治疗直至病情进展的情况。年龄≥70岁、既往奥沙利铂-氟嘧啶治疗失败的患者被随机分配（1:1）至A组（实验组）或B组（对照组）。35名患者入组后，由于毒性问题，两组的FOLFIRI剂量均降至1级。主要终点是中位无进展生存期（PFS）；次要终点是中位总生存期、客观反应率和安全性。非劣效性要求置信区间（CI）上限不超过1.5的危险比（HR）（单侧α=0.075，80%功率）。大多数患者死亡（A 组 83.5% 对 B 组 88.2%），主要死于疾病进展。A 组与 B 组的中位总生存期相似（分别为 12.2 个月和 11.5 个月）（HR = 0.89，95% CI 0.640-1.227，P = 0.467）。在维持治疗阶段，A 组与 B 组相比，严重气喘（4.5% 对 21.6%，P = 0.038）、严重不良事件（SAE）（17.8% 对 37.8%，P = 0.049）和治疗相关 SAE（6.7% 对 10.8%，P = 0.695）均有所减少。5-FU/LV-A维持治疗可减少严重气喘、SAE和治疗相关SAE。
{"title":"Maintenance with 5-FU/LV-aflibercept after induction with FOLFIRI-aflibercept versus FOLFIRI-aflibercept until progression as second-line treatment in older adults with metastatic colorectal cancer: the AFEMA phase II randomized trial","authors":"P. García-Alfonso , E. Elez , J. Soto-Alsar , D. Páez , A. Fernández-Montes , B. Graña , A. Salud , A. Yubero , M.A. Gómez-España , I. Macías , G. Quintero , C. López-López , T. Fernández-Rodríguez , C. Grávalos , E. González-Flores , M. Guix , B. García Paredes , J.J. Reina , J.R. Rodríguez Mowbray , J. Sastre , E. Aranda","doi":"10.1016/j.esmoop.2024.103986","DOIUrl":"10.1016/j.esmoop.2024.103986","url":null,"abstract":"<div><h3>Background</h3><div>The combination chemotherapy i.v. 5-fluorouracil (5-FU), irinotecan, and aflibercept (FOLFIRI-A) is a standard second-line treatment of metastatic colorectal cancer (mCRC). The aim was to assess maintenance treatment in second-line setting in older patients (aged ≥70 years) with mCRC.</div></div><div><h3>Patients and methods</h3><div>We evaluated FOLFIRI-A given for six cycles followed by maintenance with 5-FU/leucovorin (LV)-A (arm A) or FOLFIRI-A (arm B) until progression in older adults with mCRC in the AFEMA randomized, open-label, non-inferiority phase II trial (EudraCT2016-004076-21/NCT03279289). Patients aged ≥70 years who previously failed oxaliplatin-fluoropyrimidine were randomly allocated (1 : 1) to either arm A (experimental) or arm B (control). After enrolling 35 patients, the FOLFIRI dose was reduced to level 1 in both arms due to toxicity. The primary endpoint was median progression-free survival (PFS); and secondary endpoints were median overall survival, objective response rate, and safety. Non-inferiority required the upper confidence interval (CI) limit to not exceed a hazard ratio (HR) of 1.5 (one-sided <em>α</em> = 0.075, 80% power).</div></div><div><h3>Results</h3><div>A total of 170 patients were randomly allocated to arm A or arm B (<em>n</em> = 85 each). The median follow-up was 12.2 versus 10.9 months in arm A versus arm B. Most patients died (83.5% versus 88.2% in arm A versus arm B), mainly from disease progression. PFS non-inferiority was met (HR = 0.78, 95% CI 0.566-1.076, <em>P</em> = 0.131) with a median PFS of 6.1 versus 5.5 months in arm A versus arm B. Median overall survival was similar in arms A and B (12.2 and 11.5 months, respectively) (HR = 0.89, 95% CI 0.640-1.227, <em>P</em> = 0.467). During the maintenance phase, severe asthenia (4.5% versus 21.6%, <em>P</em> = 0.038), serious adverse events (SAEs) (17.8% versus 37.8%, <em>P</em> = 0.049), and treatment-related SAEs (6.7% versus 10.8%, <em>P</em> = 0.695) were reduced in arm A versus arm B.</div></div><div><h3>Conclusion</h3><div>In older adults, induction with six cycles of FOLFIRI-A plus maintenance with 5-FU/LV-A was non-inferior to FOLFIRI-A until progression. Severe asthenia, SAEs, and treatment-related SAEs were reduced with 5-FU/LV-A maintenance.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103986"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27DOI: 10.1016/j.esmoop.2024.103995
B. Vincenzi , P.P. Olimpieri , S. Celant , A. Mazzocca , A. Cortellini , A. Comandone , L. Tomassini , S. Di Segni , P. Russo , P.G. Casali
Background
Pazopanib is part of the therapeutic armamentarium for the treatment of patients with advanced non-adipocytic soft tissue sarcomas (STS) who have received prior chemotherapy, but its optimal use in STS histologies is still left to be further defined.
Design and methods
Data on STS patients treated with pazopanib in Italy have been prospectively collected from July 2013 to December 2019 through a drug monitoring registry managed by the Italian Medicines Agency (AIFA). This nationwide observational cohort study included patients with advanced STS who received pazopanib. Clinicians were mandatorily requested to fill in the AIFA monitoring registry in order to prescribe pazopanib.
Patients were recorded on the basis of their clinical characteristics, histological subtype captured at the time of treatment start, and clinical outcome. Primary outcome was time to treatment discontinuation (TTD). Secondary outcomes recorded were frequency of dose reduction and time to first dose reduction.
Results
We analyzed data from 1964 sarcoma patients. The most represented histological subtypes were leiomyosarcoma (44.7%), undifferentiated sarcomas/not otherwise specified (11.5%), and synovial sarcoma (8.1%). Overall, the median TTD was 106 days. The variables significantly associated to shorter TTD were Eastern Cooperative Oncology Group performance status (1-2 versus 0), the number of previous lines of treatment (2-4 versus 0-1) and prescribed dose (200 mg or 400 mg versus 800 mg, all once daily). Among the most represented (>20 patients) histological subtypes, we also observed longer TTD in patients with histological diagnosis of malignant solitary fibrous tumor if compared with undifferentiated sarcoma not otherwise specified.
Conclusions
In this nationwide observational real-world study, the outcomes are similar to those reported in the pivotal trial (PALETTE study). Our study includes a significant number of patients with rare/ultra-rare sarcoma subtypes and underlines possible differences in treatment duration among these histologies.
{"title":"Pazopanib in the real-world setting in soft tissue sarcomas: data from the Italian national registry","authors":"B. Vincenzi , P.P. Olimpieri , S. Celant , A. Mazzocca , A. Cortellini , A. Comandone , L. Tomassini , S. Di Segni , P. Russo , P.G. Casali","doi":"10.1016/j.esmoop.2024.103995","DOIUrl":"10.1016/j.esmoop.2024.103995","url":null,"abstract":"<div><h3>Background</h3><div>Pazopanib is part of the therapeutic armamentarium for the treatment of patients with advanced non-adipocytic soft tissue sarcomas (STS) who have received prior chemotherapy, but its optimal use in STS histologies is still left to be further defined.</div></div><div><h3>Design and methods</h3><div>Data on STS patients treated with pazopanib in Italy have been prospectively collected from July 2013 to December 2019 through a drug monitoring registry managed by the Italian Medicines Agency (AIFA). This nationwide observational cohort study included patients with advanced STS who received pazopanib. Clinicians were mandatorily requested to fill in the AIFA monitoring registry in order to prescribe pazopanib.</div><div>Patients were recorded on the basis of their clinical characteristics, histological subtype captured at the time of treatment start, and clinical outcome. Primary outcome was time to treatment discontinuation (TTD). Secondary outcomes recorded were frequency of dose reduction and time to first dose reduction.</div></div><div><h3>Results</h3><div>We analyzed data from 1964 sarcoma patients. The most represented histological subtypes were leiomyosarcoma (44.7%), undifferentiated sarcomas/not otherwise specified (11.5%), and synovial sarcoma (8.1%). Overall, the median TTD was 106 days. The variables significantly associated to shorter TTD were Eastern Cooperative Oncology Group performance status (1-2 versus 0), the number of previous lines of treatment (2-4 versus 0-1) and prescribed dose (200 mg or 400 mg versus 800 mg, all once daily). Among the most represented (>20 patients) histological subtypes, we also observed longer TTD in patients with histological diagnosis of malignant solitary fibrous tumor if compared with undifferentiated sarcoma not otherwise specified.</div></div><div><h3>Conclusions</h3><div>In this nationwide observational real-world study, the outcomes are similar to those reported in the pivotal trial (PALETTE study). Our study includes a significant number of patients with rare/ultra-rare sarcoma subtypes and underlines possible differences in treatment duration among these histologies.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103995"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27DOI: 10.1016/j.esmoop.2024.103968
N. Girard , F. Guisier , A. Swalduz , S. Van Hulst , E. Pichon , P. Lavaud , L. Greillier , A. Tiotiu , A. Madroszyk , O. Bylicki , A. Canellas , L. Belmont , M. Zysman , P.-A. Hauss , B. Godbert , C. Audigier-Valette , C. Lebreton , F. Morin , V. Westeel
Background
Small-cell lung cancer (SCLC) is a highly aggressive type of lung cancer. Lurbinectedin is recommended as second-/third-line treatment for advanced, previously treated SCLC.
Materials and methods
LURBICLIN is a nationwide, non-interventional, retrospective chart review study, based on the cohort of consecutive patients enrolled in the named patient use for lurbinectedin in France.
Results
A total of 312 patients were included. Lurbinectedin was delivered as second-line therapy in 138 (44%) patients. Grade 3-4 treatment-related adverse events were observed in 28 (9%) and 15 (5%) patients, respectively. Objective response rate (ORR) to lurbinectedin was 22% in the intention-to-treat population. After a median follow-up of 20.8 months, median progression-free survival (PFS) was 1.9 months [95% confidence interval (CI) 1.8-2.0 months]. At multivariate analysis, chemotherapy-free interval (CTFI) ≥ 90 days was an independent predictor of higher PFS [hazard ratio (HR) = 0.64, 95% CI 0.50-0.84, P < 0.0001]. The median overall survival (OS) was 4.7 months (95% CI 4.0-5.4 months). At multivariate analysis, performance status < 2 and CTFI ≥ 90 days were independent predictors of higher OS (HR = 0.71, 95% CI 0.53-0.95, P = 0.03; and HR = 0.58, 95% CI 0.44-0.76, P < 0.0001, respectively). Overall, 147 (47%) patients had initiated subsequent systemic treatments.
Conclusions
LURBICLIN confirms the activity of lurbinectedin in patients with SCLC with a manageable safety profile. Lurbinectedin monotherapy provides an alternative option for SCLC patients.
背景小细胞肺癌（SCLC）是一种侵袭性极强的肺癌。材料与方法LURBICLIN是一项全国性、非干预、回顾性病历研究，以法国使用鲁比替丁的指定患者队列为基础。138例（44%）患者接受了鲁比替丁二线治疗。分别有28例（9%）和15例（5%）患者出现3-4级治疗相关不良反应。在意向治疗人群中，鲁贝替尼的客观反应率（ORR）为22%。中位随访时间为20.8个月，中位无进展生存期（PFS）为1.9个月[95%置信区间（CI）为1.8-2.0个月]。在多变量分析中，无化疗间隔（CTFI）≥90天是较高PFS的独立预测因子[危险比（HR）=0.64，95% CI 0.50-0.84，P < 0.0001]。中位总生存期（OS）为 4.7 个月（95% CI 4.0-5.4 个月）。在多变量分析中，表现状态< 2和CTFI≥90天是较高OS的独立预测因素（HR = 0.71，95% CI 0.53-0.95，P = 0.03；HR = 0.58，95% CI 0.44-0.76，P <0.0001）。结论LURBICLIN证实了鲁贝替尼对SCLC患者的活性，且安全性可控。Lurbinectedin单药治疗为SCLC患者提供了另一种选择。
{"title":"Lurbinectedin in extensive-stage small-cell lung cancer: a brief report of the IFCT-2105 LURBICLIN study☆","authors":"N. Girard , F. Guisier , A. Swalduz , S. Van Hulst , E. Pichon , P. Lavaud , L. Greillier , A. Tiotiu , A. Madroszyk , O. Bylicki , A. Canellas , L. Belmont , M. Zysman , P.-A. Hauss , B. Godbert , C. Audigier-Valette , C. Lebreton , F. Morin , V. Westeel","doi":"10.1016/j.esmoop.2024.103968","DOIUrl":"10.1016/j.esmoop.2024.103968","url":null,"abstract":"<div><h3>Background</h3><div>Small-cell lung cancer (SCLC) is a highly aggressive type of lung cancer. Lurbinectedin is recommended as second-/third-line treatment for advanced, previously treated SCLC.</div></div><div><h3>Materials and methods</h3><div>LURBICLIN is a nationwide, non-interventional, retrospective chart review study, based on the cohort of consecutive patients enrolled in the named patient use for lurbinectedin in France.</div></div><div><h3>Results</h3><div>A total of 312 patients were included. Lurbinectedin was delivered as second-line therapy in 138 (44%) patients. Grade 3-4 treatment-related adverse events were observed in 28 (9%) and 15 (5%) patients, respectively. Objective response rate (ORR) to lurbinectedin was 22% in the intention-to-treat population. After a median follow-up of 20.8 months, median progression-free survival (PFS) was 1.9 months [95% confidence interval (CI) 1.8-2.0 months]. At multivariate analysis, chemotherapy-free interval (CTFI) ≥ 90 days was an independent predictor of higher PFS [hazard ratio (HR) = 0.64, 95% CI 0.50-0.84, <em>P</em> < 0.0001]. The median overall survival (OS) was 4.7 months (95% CI 4.0-5.4 months). At multivariate analysis, performance status < 2 and CTFI ≥ 90 days were independent predictors of higher OS (HR = 0.71, 95% CI 0.53-0.95, <em>P</em> = 0.03; and HR = 0.58, 95% CI 0.44-0.76, <em>P</em> < 0.0001, respectively). Overall, 147 (47%) patients had initiated subsequent systemic treatments.</div></div><div><h3>Conclusions</h3><div>LURBICLIN confirms the activity of lurbinectedin in patients with SCLC with a manageable safety profile. Lurbinectedin monotherapy provides an alternative option for SCLC patients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103968"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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