Pub Date : 2025-02-01DOI: 10.1016/j.ctrv.2024.102878
Philipp Melhorn, Markus Raderer, Barbara Kiesewetter
Neuroendocrine tumors (NET) of the lung are a slowly growing subtype of lung cancer that has a different treatment paradigm than aggressive and more common forms of lung neuroendocrine neoplasms (NEN) like small cell lung cancer (SCLC). Current guidelines for metastatic lung NET advocate a handful of treatment options, including somatostatin analogs (SSA), everolimus, temozolomide- or platin-based chemotherapy, and peptide receptor radionuclide therapy (PRRT). However, there is no clear treatment sequence, and the therapy of choice may depend on several factors such as tumor grade / growth rate, tumor burden / symptoms, disease progression status, and somatostatin receptor (SSTR) expression. In order to tailor treatment to each individual patient, the latest scientific findings and patient-specific clinical features must be considered together. This review critically evaluates the available evidence with regards to relevant patient characteristics, inclusion and exclusion criteria, and outcome metrics of clinical trials given the presumed natural disease course. Specific patient subgroups with an unmet therapeutic need are identified and discussed in the context of ongoing clinical trials.
{"title":"Selecting systemic treatment for metastatic neuroendocrine tumors of the lung—current evidence and clinical implications","authors":"Philipp Melhorn, Markus Raderer, Barbara Kiesewetter","doi":"10.1016/j.ctrv.2024.102878","DOIUrl":"10.1016/j.ctrv.2024.102878","url":null,"abstract":"<div><div>Neuroendocrine tumors (NET) of the lung are a slowly growing subtype of lung cancer that has a different treatment paradigm than aggressive and more common forms of lung neuroendocrine neoplasms (NEN) like small cell lung cancer (SCLC). Current guidelines for metastatic lung NET advocate a handful of treatment options, including somatostatin analogs (SSA), everolimus, temozolomide- or platin-based chemotherapy, and peptide receptor radionuclide therapy (PRRT). However, there is no clear treatment sequence, and the therapy of choice may depend on several factors such as tumor grade / growth rate, tumor burden / symptoms, disease progression status, and somatostatin receptor (SSTR) expression. In order to tailor treatment to each individual patient, the latest scientific findings and patient-specific clinical features must be considered together. This review critically evaluates the available evidence with regards to relevant patient characteristics, inclusion and exclusion criteria, and outcome metrics of clinical trials given the presumed natural disease course. Specific patient subgroups with an unmet therapeutic need are identified and discussed in the context of ongoing clinical trials.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102878"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune-based combinations are the cornerstone of the first-line treatment of metastatic renal cell carcinoma patients, leading to outstanding outcomes. Nevertheless, primary resistance and disease progression is a critical clinical challenge. To properly address this issue, it is pivotal to understand the mechanisms of resistance to immunotherapy and tyrosine kinase inhibitors, that tumor eventually develop under treatment.
In this review of the literature, we aim at exploring resistance mechanisms arising in patients treated with first-line immune-based combinations in order to understand the biological pattern that should be investigated to overcome them.
In more detail, mechanisms of resistance to nivolumab and pembrolizumab are divided into intrinsic to cancer cells and extrinsic (stromal or immune cells). Regarding axitinib, the increased expression of Nuclear protein 1 (NUPR1) or decreased levels of insulin receptor (INSR) characterize resistant cells. The secretion of non-VEGF pro-angiogenic factors, such as PDGF-BB, IL-1β, MMP-9, Gro-α, IL-8, IL-6, and CCL-2, can lead to resistance to cabozantinib. The reactivation of pathways previously targeted by lenvatinib or the activation of alternative pathways, such as EGFR-PAK2-ERK pathway, underlie the development of resistance to lenvatinib.
Exploring resistance mechanism that arise during first-line therapy can lead to the development of treatment strategy able to overcome them in order to improve duration of response and patients outcomes.
{"title":"Dynamics of resistance to immunotherapy and TKI in patients with advanced renal cell carcinoma","authors":"Matteo Santoni , Veronica Mollica , Alessandro Rizzo , Francesco Massari","doi":"10.1016/j.ctrv.2025.102881","DOIUrl":"10.1016/j.ctrv.2025.102881","url":null,"abstract":"<div><div>Immune-based combinations are the cornerstone of the first-line treatment of metastatic renal cell carcinoma patients, leading to outstanding outcomes. Nevertheless, primary resistance and disease progression is a critical clinical challenge. To properly address this issue, it is pivotal to understand the mechanisms of resistance to immunotherapy and tyrosine kinase inhibitors, that tumor eventually develop under treatment.</div><div>In this review of the literature, we aim at exploring resistance mechanisms arising in patients treated with first-line immune-based combinations in order to understand the biological pattern that should be investigated to overcome them.</div><div>In more detail, mechanisms of resistance to nivolumab and pembrolizumab are divided into intrinsic to cancer cells and extrinsic (stromal or immune cells). Regarding axitinib, the increased expression of Nuclear protein 1 (NUPR1) or decreased levels of insulin receptor (INSR) characterize resistant cells. The secretion of non-VEGF pro-angiogenic factors, such as PDGF-BB, IL-1β, MMP-9, Gro-α, IL-8, IL-6, and CCL-2, can lead to resistance to cabozantinib. The reactivation of pathways previously targeted by lenvatinib or the activation of alternative pathways, such as EGFR-PAK2-ERK pathway, underlie the development of resistance to lenvatinib.</div><div>Exploring resistance mechanism that arise during first-line therapy can lead to the development of treatment strategy able to overcome them in order to improve duration of response and patients outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"133 ","pages":"Article 102881"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-24DOI: 10.1016/j.ctrv.2025.102889
Monica K Wattana , Jonathan Rowland , Aiham Qdaisat , Hannah Levavi , Theodora Anagnostou , Larysa Sanchez , Philip Friedlander , Nicholas Rohs , Demis N. Lipe , Joshua Richter
Background
T-cell-engaging bispecific antibodies (BsAbs) are a newer type of immunotherapy designed to boost T-cell cytotoxicity. They are increasingly used in cancer treatment, with drugs currently being tested and authorized for treating both liquid and solid tumors. It’s becoming more likely that emergency physicians and other acute care practitioners will treat patients experiencing adverse events related to bispecific antibodies, as these drugs are regularly given in the outpatient setting. Currently, BsAb-associated side effects are not routinely taught to Emergency Medicine residents, and a paucity of literature exists to guide currently practicing Emergency Medicine physicians and other acute care practitioners about these medications.
Objective of the review
This review was written by emergency medicine physicians in collaboration with oncologists who routinely administer BsAbs to provide guidelines and an overview on diagnosis, treatment, and management strategies for adverse events related to bispecific antibodies.
Discussion
Side effects related to BsAbs require a multidisciplinary treatment approach ideally with oncologists notified early when an adverse event is suspected. Symptom presentation is subtle with BsAb toxicity and the main adverse events to consider working up are cytokine release syndrome, immune effector cell neurotoxicity, and infection. The article also discusses unique side effects specific to FDA-approved drugs to treat leukemia, multiple myeloma, lymphoma, lung cancer, and melanoma given that this drug class has heterogeneous receptor-specific side effects.
{"title":"Diagnosis and management of bispecific T cell–engaging antibody toxicity: A primer for emergency physicians","authors":"Monica K Wattana , Jonathan Rowland , Aiham Qdaisat , Hannah Levavi , Theodora Anagnostou , Larysa Sanchez , Philip Friedlander , Nicholas Rohs , Demis N. Lipe , Joshua Richter","doi":"10.1016/j.ctrv.2025.102889","DOIUrl":"10.1016/j.ctrv.2025.102889","url":null,"abstract":"<div><h3>Background</h3><div>T-cell-engaging bispecific antibodies (BsAbs) are a newer type of immunotherapy designed to boost T-cell cytotoxicity. They are increasingly used in cancer treatment, with drugs currently being tested and authorized for treating both liquid and solid tumors. It’s becoming more likely that emergency physicians and other acute care practitioners will treat patients experiencing adverse events related to bispecific antibodies, as these drugs are regularly given in the outpatient setting. Currently, BsAb-associated side effects are not routinely taught to Emergency Medicine residents, and a paucity of literature exists to guide currently practicing Emergency Medicine physicians and other acute care practitioners about these medications.</div></div><div><h3>Objective of the review</h3><div>This review was written by emergency medicine physicians in collaboration with oncologists who routinely administer BsAbs to provide guidelines and an overview on diagnosis, treatment, and management strategies for adverse events related to bispecific antibodies.</div></div><div><h3>Discussion</h3><div>Side effects related to BsAbs require a multidisciplinary treatment approach ideally with oncologists notified early when an adverse event is suspected. Symptom presentation is subtle with BsAb toxicity and the main adverse events to consider working up are cytokine release syndrome, immune effector cell neurotoxicity, and infection. The article also discusses unique side effects specific to FDA-approved drugs to treat leukemia, multiple myeloma, lymphoma, lung cancer, and melanoma given that this drug class has heterogeneous receptor-specific side effects.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"134 ","pages":"Article 102889"},"PeriodicalIF":9.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143223576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuroendocrine carcinomas are rare and aggressive malignancies, often diagnosed at advanced stages, leading to poor prognosis. Platinum-based chemotherapy is the standard first-line treatment for advanced neuroendocrine carcinomas; however after achieving response no consensus exists on maintenance therapies and the results are inconsistent. This review examines the role of maintenance therapy following response to first-line chemotherapy in gastroenteropancreatic neuroendocrine carcinomas. We identified limited supporting evidence, primarily from phase II trials and case reports, that suggested maintenance therapy could be considered for prolonging progression-free survival, balancing toxicity, and maintaining quality of life. Nevertheless, prospective studies are needed to validate its clinical efficacy.
{"title":"Maintenance therapy after first-line platinum-based chemotherapy in gastroenteropancreatic neuroendocrine carcinomas: A literature review","authors":"Natalia Soledad Tissera , Francesca Balconi , Alejandro García-Álvarez , Jorge Hernando Cubero , Juan Manuel O'Connor , Matías Chacón , Jaume Capdevila","doi":"10.1016/j.ctrv.2024.102863","DOIUrl":"10.1016/j.ctrv.2024.102863","url":null,"abstract":"<div><div>Neuroendocrine carcinomas are rare and aggressive malignancies, often diagnosed at advanced stages, leading to poor prognosis. Platinum-based chemotherapy is the standard first-line treatment for advanced neuroendocrine carcinomas; however after achieving response no consensus exists on maintenance therapies and the results are inconsistent. This review examines the role of maintenance therapy following response to first-line chemotherapy in gastroenteropancreatic neuroendocrine carcinomas. We identified limited supporting evidence, primarily from phase II trials and case reports, that suggested maintenance therapy could be considered for prolonging progression-free survival, balancing toxicity, and maintaining quality of life. Nevertheless, prospective studies are needed to validate its clinical efficacy.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102863"},"PeriodicalIF":9.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a poor prognosis, and the majority of patients with HNSCC are diagnosed at later stages owing to its hidden anatomical location and atypical clinical symptoms. It is notably prone to recurrence and metastasis. The traditional treatments include surgery, radiotherapy, chemotherapy, and targeted therapy. Although multiple treatment strategies have been established, the prognosis remains poor because most patients develop resistance to traditional treatments. In recent years, epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint inhibitors (ICIs) have been shown to provide clinical benefits to these patients. Based on the promising results of both anti-EGFR therapy and immunotherapy, as well as the biological rationale for combining immunotherapy with anti-EGFR drugs, numerous preclinical and ongoing or completed clinical trials have explored the use of their synergistic effects. This review summarizes the feasibility of combining immunotherapy with EGFR inhibitors for HNSCC treatment and analyses the relevant biomarkers. It also summarizes the strategies for clinical applications. We found that immunotherapy and EGFR inhibitor combination therapy showed promise in treating patients with HNSCC and exhibited safety with acceptable adverse events. This review may provide valuable insights for the future development of treatments and formulation of therapeutic strategies for HNSCC, as well as useful information for the future design of clinical trials.
{"title":"Current status and future prospects of combined immunotherapy and epidermal growth factor receptor inhibitors in head and neck squamous cell carcinoma","authors":"Xin Tian , Hongyan Zhang , Yiman Han , Baoru Gu , Zhenyong Zhang","doi":"10.1016/j.ctrv.2024.102864","DOIUrl":"10.1016/j.ctrv.2024.102864","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a poor prognosis, and the majority of patients with HNSCC are diagnosed at later stages owing to its hidden anatomical location and atypical clinical symptoms. It is notably prone to recurrence and metastasis. The traditional treatments include surgery, radiotherapy, chemotherapy, and targeted therapy. Although multiple treatment strategies have been established, the prognosis remains poor because most patients develop resistance to traditional treatments. In recent years, epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint inhibitors (ICIs) have been shown to provide clinical benefits to these patients. Based on the promising results of both anti-EGFR therapy and immunotherapy, as well as the biological rationale for combining immunotherapy with anti-EGFR drugs, numerous preclinical and ongoing or completed clinical trials have explored the use of their synergistic effects. This review summarizes the feasibility of combining immunotherapy with EGFR inhibitors for HNSCC treatment and analyses the relevant biomarkers. It also summarizes the strategies for clinical applications. We found that immunotherapy and EGFR inhibitor combination therapy showed promise in treating patients with HNSCC and exhibited safety with acceptable adverse events. This review may provide valuable insights for the future development of treatments and formulation of therapeutic strategies for HNSCC, as well as useful information for the future design of clinical trials.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102864"},"PeriodicalIF":9.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.ctrv.2024.102861
Chunfang Hao , Yunchu Wei , Wenjing Meng , Jie Zhang , Xiaonan Yang
Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays a pivotal role in the development and progression of various cancers. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, aberrations in this pathway are increasingly recognized as key drivers of resistance to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, the first-line treatments for this disease subtype. Recognizing the urgent need for alternative therapeutic strategies, significant advancements have been made in developing PI3K/AKT/mTOR inhibitors for HR+ advanced/metastatic breast cancer. Among these inhibitors, capivasertib and alpelisib have received approval as targeted therapies for this indication. This review provides a comprehensive summary of the latest developments in PI3K/AKT/mTOR inhibitors for HR+ breast cancer. It also delves into different aspects, including sampling, testing method and timing, of PI3K/AKT/mTOR diagnostic testing. Additionally, the review discusses key considerations for integrating these inhibitors into clinical practice, such as timing and choice of PI3K/AKT/mTOR inhibitors, and management of treatment toxicities. By examining these different aspects, this review aims to provide valuable insights into optimizing the clinical utility of PI3K/AKT/mTOR inhibitors in HR+ advanced breast cancer.
{"title":"PI3K/AKT/mTOR inhibitors for hormone receptor-positive advanced breast cancer","authors":"Chunfang Hao , Yunchu Wei , Wenjing Meng , Jie Zhang , Xiaonan Yang","doi":"10.1016/j.ctrv.2024.102861","DOIUrl":"10.1016/j.ctrv.2024.102861","url":null,"abstract":"<div><div>Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays a pivotal role in the development and progression of various cancers. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, aberrations in this pathway are increasingly recognized as key drivers of resistance to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, the first-line treatments for this disease subtype. Recognizing the urgent need for alternative therapeutic strategies, significant advancements have been made in developing PI3K/AKT/mTOR inhibitors for HR+ advanced/metastatic breast cancer. Among these inhibitors, capivasertib and alpelisib have received approval as targeted therapies for this indication. This review provides a comprehensive summary of the latest developments in PI3K/AKT/mTOR inhibitors for HR+ breast cancer. It also delves into different aspects, including sampling, testing method and timing, of PI3K/AKT/mTOR diagnostic testing. Additionally, the review discusses key considerations for integrating these inhibitors into clinical practice, such as timing and choice of PI3K/AKT/mTOR inhibitors, and management of treatment toxicities. By examining these different aspects, this review aims to provide valuable insights into optimizing the clinical utility of PI3K/AKT/mTOR inhibitors in HR+ advanced breast cancer.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102861"},"PeriodicalIF":9.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.ctrv.2024.102865
Francesco Schettini , Sabrina Nucera , Tomás Pascual , Olga Martínez-Sáez , Rodrigo Sánchez-Bayona , Benedetta Conte , Giuseppe Buono , Matteo Lambertini , Kevin Punie , Juan Miguel Cejalvo , Grazia Arpino , Paolo Vigneri , Daniele Generali , Eva Ciruelos , Javier Cortés , Alessandra Gennari , Montserrat Muñoz , Maria J. Vidal Losada , Sara M Tolaney , Aleix Prat , Guillermo Villacampa
Introduction
Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd).
Methods
We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+ and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd. Hazard ratios (HRs) with 95 % confidence intervals (CI) were calculated for PFS/OS. P-score was used for treatment ranking.
Results
Three RCTs (956 patients) were included in the primary analysis and 5 (1,445) in the exploratory NMA with Dato-DXd. In HR+/HER2-low, T-DXd showed no significant difference in PFS and OS when compared to SG. Similarly, in TN/HER2-low, PFS and OS did not differ significantly between the two ADCs. The P-score analysis favored T-DXd over SG in HR+/HER2-low in PFS (0.90 vs. 0.60) and OS (0.89 vs. 0.60). SG was favored over T-DXd in OS in TN/HER2-low (0.80 vs. 0.69). Similar results were obtained for HR+ MBC when including Dato-Dxd, which showed the worst performance, while T-DXd was the only ADC significantly outperforming CT in OS. The ADCs showed significantly better PFS and OS than CT in HR+/HER2-low and TN/HER2-low (all p < 0.001). SG had higher rates of neutropenia, diarrhea and alopecia vs. T-DXd, which showed more thrombocytopenia, fatigue and nausea. Pneumonitis and cardiotoxicity were typically T-DXd-related, and T-DXd showed more toxicity-related discontinuations.
Conclusions
Similar efficacy with T-DXd and SG in HER2-low MBC was observed, regardless of HR status. Safety profile, local drug-approval criteria and guidelines, patients’ preferences and overall quality of evidence should ultimately guide therapeutic decision-making. Dato-DXd role remains uncertain.
抗体-药物偶联物（adc）曲妥珠单抗-德鲁西替康（T-DXd）和sacituzumab-govitecan （SG）在预处理激素受体阳性（HR+）和三阴性(TN)/ her2低转移性乳腺癌（MBC）中，比化疗（CT）提供了显著的无进展生存期（PFS）和总生存期（OS）改善。然而，两者之间没有直接的比较，也没有与最近的datopotamab-deruxtecan （Dato-DXd）进行比较。方法：通过网络荟萃分析（NMA）比较T-DXd和SG在CT预处理的HR+和TN/ her2低MBC中的疗效和安全性，并评估其相对于标准CT的益处，同时探讨与Dato-DXd的比较。计算PFS/OS的风险比（hr）和95%置信区间（CI）。采用P-score进行治疗排序。结果：3个随机对照试验（956例）被纳入初级分析，5个随机对照试验（1445例）被纳入探索性NMA与Dato-DXd。在HR+/HER2-low组，T-DXd组与SG组相比PFS和OS无显著差异。同样，在TN/ her2低的情况下，两种adc的PFS和OS无显著差异。p评分分析表明，在HR+/ her2低的PFS （0.90 vs 0.60）和OS （0.89 vs 0.60）中，T-DXd优于SG。在TN/ her2低的OS中，SG优于T-DXd （0.80 vs 0.69）。HR+ MBC在加入Dato-Dxd后也得到了类似的结果，Dato-Dxd表现最差，而T-DXd是OS中唯一表现明显优于CT的ADC。在HR+/ her2低和TN/ her2低的情况下，adc的PFS和OS明显优于CT（均为p）。结论：无论HR状态如何，在her2低的MBC中，T-DXd和SG的疗效相似。安全性概况、当地药物批准标准和指南、患者偏好和总体证据质量应最终指导治疗决策。Dato-DXd的作用仍然不确定。
{"title":"Efficacy and safety of antibody-drug conjugates in pretreated HER2-low metastatic breast cancer: A systematic review and network meta-analysis","authors":"Francesco Schettini , Sabrina Nucera , Tomás Pascual , Olga Martínez-Sáez , Rodrigo Sánchez-Bayona , Benedetta Conte , Giuseppe Buono , Matteo Lambertini , Kevin Punie , Juan Miguel Cejalvo , Grazia Arpino , Paolo Vigneri , Daniele Generali , Eva Ciruelos , Javier Cortés , Alessandra Gennari , Montserrat Muñoz , Maria J. Vidal Losada , Sara M Tolaney , Aleix Prat , Guillermo Villacampa","doi":"10.1016/j.ctrv.2024.102865","DOIUrl":"10.1016/j.ctrv.2024.102865","url":null,"abstract":"<div><h3>Introduction</h3><div>Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd).</div></div><div><h3>Methods</h3><div>We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+ and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd. Hazard ratios (HRs) with 95 % confidence intervals (CI) were calculated for PFS/OS. P-score was used for treatment ranking.</div></div><div><h3>Results</h3><div>Three RCTs (956 patients) were included in the primary analysis and 5 (1,445) in the exploratory NMA with Dato-DXd. In HR+/HER2-low, T-DXd showed no significant difference in PFS and OS when compared to SG. Similarly, in TN/HER2-low, PFS and OS did not differ significantly between the two ADCs. The P-score analysis favored T-DXd over SG in HR+/HER2-low in PFS (0.90 vs. 0.60) and OS (0.89 vs. 0.60). SG was favored over T-DXd in OS in TN/HER2-low (0.80 vs. 0.69). Similar results were obtained for HR+ MBC when including Dato-Dxd, which showed the worst performance, while T-DXd was the only ADC significantly outperforming CT in OS. The ADCs showed significantly better PFS and OS than CT in HR+/HER2-low and TN/HER2-low (all p < 0.001). SG had higher rates of neutropenia, diarrhea and alopecia vs. T-DXd, which showed more thrombocytopenia, fatigue and nausea. Pneumonitis and cardiotoxicity were typically T-DXd-related, and T-DXd showed more toxicity-related discontinuations.</div></div><div><h3>Conclusions</h3><div>Similar efficacy with T-DXd and SG in HER2-low MBC was observed, regardless of HR status. Safety profile, local drug-approval criteria and guidelines, patients’ preferences and overall quality of evidence should ultimately guide therapeutic decision-making. Dato-DXd role remains uncertain.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102865"},"PeriodicalIF":9.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.1016/j.ctrv.2024.102860
Volkmar Müller , Thomas Bachelot , Giuseppe Curigliano , Evandro de Azambuja , Julia Furtner , Jens Gempt , Barbara Alicja Jereczek-Fossa , Katarzyna J. Jerzak , Emilie Le Rhun , Carlo Palmieri , Gabriella Pravettoni , Cristina Saura , Rupert Bartsch
Background
Patients with HER2-positive breast cancer have a significant risk of developing brain metastases (BrM), which have detrimental effects on survival outcomes and quality of life. Although there are several systemic treatment options available that may delay the appearance of BrM and secondary progression of previously treated BrM, there are still substantial unmet needs for this patient population and primary prevention remains elusive.
Methods
A group of experts created consensus statements, through a modified Delphi process, to bridge the gap between current unmet needs, available evidence, and international guidelines.
Results
The steering committee reviewed all relevant literature and formed research questions to be answered by the subsequent consensus statements. In total, 61 contributors provided feedback on the consensus statements, with 34 statements reaching agreement out of the 55 statements that were voted on altogether. Statements with consensus aimed to define BrM primary and secondary prevention, screening procedures, assessment of symptoms, treatment efficacy, and preventing the occurrence and progression of BrM, while acknowledging the possibilities and limitations in daily clinical practice. Some statements did not reach agreement for a variety of reasons, mostly due to lack of evidence.
Conclusions
The consensus statements outlined in this publication provide a point of reference for daily clinical practice and can act as recommendations for clinical trial procedures and future guidelines.
{"title":"Expert consensus on the prevention of brain metastases in patients with HER2-positive breast cancer","authors":"Volkmar Müller , Thomas Bachelot , Giuseppe Curigliano , Evandro de Azambuja , Julia Furtner , Jens Gempt , Barbara Alicja Jereczek-Fossa , Katarzyna J. Jerzak , Emilie Le Rhun , Carlo Palmieri , Gabriella Pravettoni , Cristina Saura , Rupert Bartsch","doi":"10.1016/j.ctrv.2024.102860","DOIUrl":"10.1016/j.ctrv.2024.102860","url":null,"abstract":"<div><h3>Background</h3><div>Patients with HER2-positive breast cancer have a significant risk of developing brain metastases (BrM), which have detrimental effects on survival outcomes and quality of life. Although there are several systemic treatment options available that may delay the appearance of BrM and secondary progression of previously treated BrM, there are still substantial unmet needs for this patient population and primary prevention remains elusive.</div></div><div><h3>Methods</h3><div>A group of experts created consensus statements, through a modified Delphi process, to bridge the gap between current unmet needs, available evidence, and international guidelines.</div></div><div><h3>Results</h3><div>The steering committee reviewed all relevant literature and formed research questions to be answered by the subsequent consensus statements. In total, 61 contributors provided feedback on the consensus statements, with 34 statements reaching agreement out of the 55 statements that were voted on altogether. Statements with consensus aimed to define BrM primary and secondary prevention, screening procedures, assessment of symptoms, treatment efficacy, and preventing the occurrence and progression of BrM, while acknowledging the possibilities and limitations in daily clinical practice. Some statements did not reach agreement for a variety of reasons, mostly due to lack of evidence.</div></div><div><h3>Conclusions</h3><div>The consensus statements outlined in this publication provide a point of reference for daily clinical practice and can act as recommendations for clinical trial procedures and future guidelines.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102860"},"PeriodicalIF":9.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14DOI: 10.1016/j.ctrv.2024.102853
Rupert Bartsch , David Cameron , Eva Ciruelos , Carmen Criscitiello , Giuseppe Curigliano , Francois P Duhoux , Theodoros Foukakis , Joseph Gligorov , Nadia Harbeck , Nathalie LeVasseur , Alicia Okines , Frederique Penault-Llorca , Volkmar Müller
Human epidermal growth factor receptor 2 (HER2) overexpression and/or ERBB2 gene amplification occurs in approximately 15–20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer. However, in the third-line treatment setting and beyond, there is a lack of clarity of the preferred choice of therapy. In clinical practice, clinicians may also encounter challenging scenarios where the optimal therapeutic approach has not been defined by clinical studies, so there is a need for clarity in such situations. Two consensus meetings of expert oncologists (12 from Europe and one from Canada) were convened to discuss these scenarios. We subsequently developed this article to present an overview of current treatment recommendations for HER2-positive metastatic breast cancer and give practical guidance on addressing challenging scenarios in a real-world setting. Based on our clinical experience, we provide a unanimous consensus concerning the treatment of elderly patients as well as those with brain-only metastases, leptomeningeal disease, oligometastatic disease, central nervous system oligo-progressive disease or ERBB2-mutant disease. We also discuss how to combine HER2-targeted therapy with endocrine therapy in patients with HER2-positive/hormone-receptor-positive disease, considerations for potential discontinuation of HER2-targeted therapy in patients with long-term remission and how to treat patients whose metastatic biopsy no longer confirms their HER2-positive status.
{"title":"Expert recommendations on treatment sequencing and challenging clinical scenarios in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer","authors":"Rupert Bartsch , David Cameron , Eva Ciruelos , Carmen Criscitiello , Giuseppe Curigliano , Francois P Duhoux , Theodoros Foukakis , Joseph Gligorov , Nadia Harbeck , Nathalie LeVasseur , Alicia Okines , Frederique Penault-Llorca , Volkmar Müller","doi":"10.1016/j.ctrv.2024.102853","DOIUrl":"10.1016/j.ctrv.2024.102853","url":null,"abstract":"<div><div>Human epidermal growth factor receptor 2 (HER2) overexpression and/or <em>ERBB2</em> gene amplification occurs in approximately 15–20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer. However, in the third-line treatment setting and beyond, there is a lack of clarity of the preferred choice of therapy. In clinical practice, clinicians may also encounter challenging scenarios where the optimal therapeutic approach has not been defined by clinical studies, so there is a need for clarity in such situations. Two consensus meetings of expert oncologists (12 from Europe and one from Canada) were convened to discuss these scenarios. We subsequently developed this article to present an overview of current treatment recommendations for HER2-positive metastatic breast cancer and give practical guidance on addressing challenging scenarios in a real-world setting. Based on our clinical experience, we provide a unanimous consensus concerning the treatment of elderly patients as well as those with brain-only metastases, leptomeningeal disease, oligometastatic disease, central nervous system oligo-progressive disease or <em>ERBB2</em>-mutant disease. We also discuss how to combine HER2-targeted therapy with endocrine therapy in patients with HER2-positive/hormone-receptor-positive disease, considerations for potential discontinuation of HER2-targeted therapy in patients with long-term remission and how to treat patients whose metastatic biopsy no longer confirms their HER2-positive status.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102853"},"PeriodicalIF":9.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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