Pub Date : 2026-02-01DOI: 10.1016/j.ctrv.2026.103091
Yuwei Li , Kaiyan Chen , Hui Li , Yun Fan
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour with a poor prognosis. Although treatment regimens such as first-line immunochemotherapy have shown clinical benefits in extensive stage SCLC (ES-SCLC), patients still face disease recurrence and drug resistance. Antibody-drug conjugates (ADCs) are new therapeutic compounds made up of a monoclonal antibody (mAb) attached to a cytotoxic drug (payload) using a linker. They achieve precise killing of tumour cells by conjugating highly cytotoxic drugs with monoclonal antibodies targeting specific tumour antigens. In recent years, antigens such as B7-H3, Trop-2, SEZ6, DLL3, and EGFR–HER3 have become primary targets for ADC development in ES-SCLC. Although some ADCs have been limited due to toxicity-related issues, numerous other ADCs have entered clinical trial phases and demonstrated encouraging efficacy, with ORRs of 33.3 %–68.0 % and median PFS of 4.0–7.6 months. In this review, we systematically summarize ADCs currently in clinical trials and preclinical research for SCLC, and comprehensively discuss their pharmacodynamic characteristics, therapeutic effects, adverse effects, and strategies for optimising treatment.
{"title":"Targeted precision Strike in Extensive-Stage small cell lung Cancer: Current advances and future Perspectives for Antibody–Drug conjugates","authors":"Yuwei Li , Kaiyan Chen , Hui Li , Yun Fan","doi":"10.1016/j.ctrv.2026.103091","DOIUrl":"10.1016/j.ctrv.2026.103091","url":null,"abstract":"<div><div>Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour with a poor prognosis. Although treatment regimens such as first-line immunochemotherapy have shown clinical benefits in extensive stage SCLC (ES-SCLC), patients still face disease recurrence and drug resistance. Antibody-drug conjugates (ADCs) are new therapeutic compounds made up of a monoclonal antibody (mAb) attached to a cytotoxic drug (payload) using a linker. They achieve precise killing of tumour cells by conjugating highly cytotoxic drugs with monoclonal antibodies targeting specific tumour antigens. In recent years, antigens such as B7-H3, Trop-2, SEZ6, DLL3, and EGFR–HER3 have become primary targets for ADC development in ES-SCLC. Although some ADCs have been limited due to toxicity-related issues, numerous other ADCs have entered clinical trial phases and demonstrated encouraging efficacy, with ORRs of 33.3 %–68.0 % and median PFS of 4.0–7.6 months. In this review, we systematically summarize ADCs currently in clinical trials and preclinical research for SCLC, and comprehensively discuss their pharmacodynamic characteristics, therapeutic effects, adverse effects, and strategies for optimising treatment.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103091"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073584","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 : 2026-01-28DOI: 10.1016/j.ctrv.2026.103096
Maria Ibáñez Alda , Thomas Grinda , Barbara Pistilli
Antibody-drug conjugates (ADCs) are a new class of targeted therapies that have demonstrated clinical benefit across various tumor types and disease stages. In breast cancer, following their success in the metastatic setting, ADCs show improved antitumor activity with potentially reduced systemic toxicity, making them a promising option in the neoadjuvant treatment of early breast cancer. This review examines the evolving role of ADCs in early breast cancer, highlighting emerging clinical trial data, innovative trial designs, and the integration of biomarkers, all aimed at optimizing patient outcomes and personalizing neoadjuvant strategies across different breast cancer subtypes.
{"title":"Integrating antibody-drug conjugates into the management of early breast cancer","authors":"Maria Ibáñez Alda , Thomas Grinda , Barbara Pistilli","doi":"10.1016/j.ctrv.2026.103096","DOIUrl":"10.1016/j.ctrv.2026.103096","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) are a new class of targeted therapies that have demonstrated clinical benefit across various tumor types and disease stages. In breast cancer, following their success in the metastatic setting, ADCs show improved antitumor activity with potentially reduced systemic toxicity, making them a promising option in the neoadjuvant treatment of early breast cancer. This review examines the evolving role of ADCs in early breast cancer, highlighting emerging clinical trial data, innovative trial designs, and the integration of biomarkers, all aimed at optimizing patient outcomes and personalizing neoadjuvant strategies across different breast cancer subtypes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"144 ","pages":"Article 103096"},"PeriodicalIF":10.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146135748","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 : 2026-01-20DOI: 10.1016/j.ctrv.2026.103095
Tiia Snäkä , Alex Friedlaender , Michele Graciotti , Miriam Hernandez , Laetitia Rossier , Volker Kirchner , Lana Kandalaft
Cancer vaccines have matured significantly with advances in antigen discovery, delivery platforms, and personalized design driven by breakthroughs in genomics and artificial intelligence − yet they remain underutilized in clinical oncology. A growing body of evidence now demonstrates that the key to unlocking their full potential lies not in using them in isolation, but in strategically combining them with other treatment modalities. Vaccines exert their greatest efficacy when administered during defined immunologic windows—periods in which the patient’s immune system is most amenable to activation and durable antigen-specific priming. Crucially, combination with standard-of-care (SOC) therapies such as chemotherapy, radiotherapy, and immune checkpoint inhibitors can generate synergistic effects that reshape the tumor–immune interface. Cytotoxic and targeted agents can enhance antigen release, modulate the tumor microenvironment, and promote immune infiltration, thereby creating a more permissive milieu for vaccine-induced responses. In reciprocity, vaccination can potentiate the efficacy of SOC regimens by amplifying tumor-specific immunity, counteracting resistance mechanisms, and sustaining immune surveillance. Thus, the emerging paradigm positions cancer vaccines not as standalone interventions, but as integral components of a multimodal therapeutic architecture. Strategic co-deployment of vaccines within SOC frameworks represents a scientifically grounded and clinically actionable approach to achieving durable tumor control and long-term remission in patients with solid malignancies. This review delineates the mechanistic rationale and clinical evidence supporting such integration across the continuum of disease stages.
{"title":"Personalized cancer vaccines and their integration with standard of care modalities","authors":"Tiia Snäkä , Alex Friedlaender , Michele Graciotti , Miriam Hernandez , Laetitia Rossier , Volker Kirchner , Lana Kandalaft","doi":"10.1016/j.ctrv.2026.103095","DOIUrl":"10.1016/j.ctrv.2026.103095","url":null,"abstract":"<div><div>Cancer vaccines have matured significantly with advances in antigen discovery, delivery platforms, and personalized design driven by breakthroughs in genomics and artificial intelligence − yet they remain underutilized in clinical oncology. A growing body of evidence now demonstrates that the key to unlocking their full potential lies not in using them in isolation, but in strategically combining them with other treatment modalities. Vaccines exert their greatest efficacy when administered during defined immunologic windows—periods in which the patient’s immune system is most amenable to activation and durable antigen-specific priming. Crucially, combination with standard-of-care (SOC) therapies such as chemotherapy, radiotherapy, and immune checkpoint inhibitors can generate synergistic effects that reshape the tumor–immune interface. Cytotoxic and targeted agents can enhance antigen release, modulate the tumor microenvironment, and promote immune infiltration, thereby creating a more permissive milieu for vaccine-induced responses. In reciprocity, vaccination can potentiate the efficacy of SOC regimens by amplifying tumor-specific immunity, counteracting resistance mechanisms, and sustaining immune surveillance. Thus, the emerging paradigm positions cancer vaccines not as standalone interventions, but as integral components of a multimodal therapeutic architecture. Strategic co-deployment of vaccines within SOC frameworks represents a scientifically grounded and clinically actionable approach to achieving durable tumor control and long-term remission in patients with solid malignancies. This review delineates the mechanistic rationale and clinical evidence supporting such integration across the continuum of disease stages.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103095"},"PeriodicalIF":10.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023378","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 : 2026-01-16DOI: 10.1016/j.ctrv.2026.103092
Irene Persano , Luca Licata , Marta Piras , Arisa Ata-Shiroshita , Matteo Maria Naldini , Carlo Bosi , Giulia Notini , Marco Mariani , Antonella Chiavassa , Francesca Patanè , Caterina Zanibelli , Alessia Rognone , Lorenzo Sica , Stefania Zambelli , Patrizia Zucchinelli , Alessandra Guarino , Marcella Pasetti , Rosa Di Micco , Oreste Davide Gentilini , Giampaolo Bianchini , Giulia Viale
The recognition that axillary surgery in early breast cancer primarily serves as a staging tool rather than a curative treatment, along with the shift from axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB) as the standard procedure for clinically node-negative patients, has paved the way for further de-escalation of axillary treatment. This strategy aims to reduce treatment-related morbidity while preserving survival outcomes. Multiple studies have provided compelling evidence that ALND can be safely omitted in cases of limited SLN involvement. Moreover, even the omission of SLNB in selected low-risk cohorts has been shown not to increase recurrence rates. On the other side, from the oncological perspective, research has moved toward an escalation of adjuvant treatments, aiming to reduce recurrence rates and improve overall survival. Thus, while residual axillary disease does not affect patient outcomes, limited axillary staging may hinder access to certain adjuvant therapies. Here, we aim to critically assess the potential impact of recent advances in axillary surgical de-escalation on adjuvant systemic therapy decision-making especially in hormone receptor positive/HER2 negative early breast cancer, with a particular focus on the appropriate selection of patients for adjuvant chemotherapy, CDK4/6 inhibitors, and PARP inhibitors. We argue that decisions on surgical de-escalation should be carefully tailored, balancing its potential benefits with the need for accurate staging to guide adjuvant therapies. A patient-centered, multidisciplinary approach remains essential to ensure that de-escalation does not impact negatively on adjuvant treatment decision making and long-term survival.
{"title":"De-escalation strategies for axillary management at primary surgery in early breast cancer: insights and implications for medical oncology practice","authors":"Irene Persano , Luca Licata , Marta Piras , Arisa Ata-Shiroshita , Matteo Maria Naldini , Carlo Bosi , Giulia Notini , Marco Mariani , Antonella Chiavassa , Francesca Patanè , Caterina Zanibelli , Alessia Rognone , Lorenzo Sica , Stefania Zambelli , Patrizia Zucchinelli , Alessandra Guarino , Marcella Pasetti , Rosa Di Micco , Oreste Davide Gentilini , Giampaolo Bianchini , Giulia Viale","doi":"10.1016/j.ctrv.2026.103092","DOIUrl":"10.1016/j.ctrv.2026.103092","url":null,"abstract":"<div><div>The recognition that axillary surgery in early breast cancer primarily serves as a staging tool rather than a curative treatment, along with the shift from axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB) as the standard procedure for clinically node-negative patients, has paved the way for further de-escalation of axillary treatment. This strategy aims to reduce treatment-related morbidity while preserving survival outcomes. Multiple studies have provided compelling evidence that ALND can be safely omitted in cases of limited SLN involvement. Moreover, even the omission of SLNB in selected low-risk cohorts has been shown not to increase recurrence rates. On the other side, from the oncological perspective, research has moved toward an escalation of adjuvant treatments, aiming to reduce recurrence rates and improve overall survival. Thus, while residual axillary disease does not affect patient outcomes, limited axillary staging may hinder access to certain adjuvant therapies. Here, we aim to critically assess the potential impact of recent advances in axillary surgical de-escalation on adjuvant systemic therapy decision-making especially in hormone receptor positive/HER2 negative early breast cancer, with a particular focus on the appropriate selection of patients for adjuvant chemotherapy, CDK4/6 inhibitors, and PARP inhibitors. We argue that decisions on surgical de-escalation should be carefully tailored, balancing its potential benefits with the need for accurate staging to guide adjuvant therapies. A patient-centered, multidisciplinary approach remains essential to ensure that de-escalation does not impact negatively on adjuvant treatment decision making and long-term survival.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103092"},"PeriodicalIF":10.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023377","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}
NRAS mutations are present in 15–25 % of cutaneous melanomas, predominantly affecting codon 61 (Q61R > Q61K). Mutations at codons 12 and 13 are rare although they appear to be relatively enriched in mucosal subtype. KRAS alterations, while rare in cutaneous melanomas, are more frequently observed in melanoma brain metastases as well as in acral and mucosal subtypes, where NRAS mutations are less prevalent. For advanced RAS-mutant melanoma, systemic therapy currently relies on anti-PD-1-based immune checkpoint inhibition. MEK inhibitors have demonstrated only modest clinical benefit due to the development of resistance and are not approved outside of China for this subtype. Ongoing combination strategies include MEK inhibition with type II RAF inhibitors (naporafenib plus trametinib in phase III trial), ERK1/2 or ERK5 inhibitors, PI3K/mTOR pathway blockade, or CDK4/6 inhibition. Additional investigational approaches include mutation-specific RAS inhibitors (G12C inhibitors already approved for other cancers), NRAS-specific or pan-RAS inhibitors (daraxonrasib in phase III trial for other cancers), targeted protein degradation, RAS-directed peptide and mRNA vaccines (mRNA-4157). NRAS Q61K-derived neoepitopes bound to HLA-A*01:01 have been recognized as immunogenic, suggesting that mutation-specific immunotherapies could represent a promising future strategy. In conclusion, the advent of promising and emerging therapies is set to transform the management of RAS-driven melanoma, making a personalized, biomarker-informed treatment strategy essential for optimizing patient outcomes.
{"title":"Insights into RAS-driven melanoma and its therapeutic implications","authors":"Eftychia Chatziioannou , Konstantinos Lallas , Tobias Sinnberg , Heike Niessner , Alexander J. Stratigos , Lukas Flatz , Teresa Amaral","doi":"10.1016/j.ctrv.2026.103090","DOIUrl":"10.1016/j.ctrv.2026.103090","url":null,"abstract":"<div><div><em>NRAS</em> mutations are present in 15–25 % of cutaneous melanomas, predominantly affecting codon 61 (Q61R > Q61K). Mutations at codons 12 and 13 are rare although they appear to be relatively enriched in mucosal subtype. <em>KRAS</em> alterations, while rare in cutaneous melanomas, are more frequently observed in melanoma brain metastases as well as in acral and mucosal subtypes, where <em>NRAS</em> mutations are less prevalent. For advanced <em>RAS</em>-mutant melanoma, systemic therapy currently relies on anti-PD-1-based immune checkpoint inhibition. MEK inhibitors have demonstrated only modest clinical benefit due to the development of resistance and are not approved outside of China for this subtype. Ongoing combination strategies include MEK inhibition with type II RAF inhibitors (naporafenib plus trametinib in phase III trial), ERK1/2 or ERK5 inhibitors, PI3K/mTOR pathway blockade, or CDK4/6 inhibition. Additional investigational approaches include mutation-specific RAS inhibitors (G12C inhibitors already approved for other cancers), NRAS-specific or pan-RAS inhibitors (daraxonrasib in phase III trial for other cancers), targeted protein degradation, RAS-directed peptide and mRNA vaccines (mRNA-4157). <em>NRAS</em> Q61K-derived neoepitopes bound to HLA-A*01:01 have been recognized as immunogenic, suggesting that mutation-specific immunotherapies could represent a promising future strategy. In conclusion, the advent of promising and emerging therapies is set to transform the management of RAS-driven melanoma, making a personalized, biomarker-informed treatment strategy essential for optimizing patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103090"},"PeriodicalIF":10.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023376","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 : 2026-01-12DOI: 10.1016/j.ctrv.2026.103093
Najwaa Kirmani , Nathalia De León-Fernández , Juan David Rodriguez-Parra , Laura Ghanem , Bezalel Hakkeem , Clara Briceño-Morales , Ximena Briceño-Morales
Background
Endocrine therapy (ET) plus CDK4/6 inhibitors (CDK4/6i) remains first-line (1 L) standard for ER+/HER2– metastatic breast cancer (mBC). However, ESR1 mutations lead to ET resistance and subsequent disease progression (PD). Limitations of intramuscular fulvestrant have led to the development of novel oral selective estrogen receptor degraders (SERDs). We aim to evaluate efficacy and safety of novel oral SERDs for ER+/HER2– mBC.
Methods
PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials (RCTs) comparing oral SERDs with standard treatment. Primary outcomes were progression-free survival (PFS) overall and by subgroups (ESR1 mutation, menopausal status, age, prior CDK4/6i use, visceral metastases), PFS comparing oral SERDs versus fulvestrant in ESR1-mutated patients, and grade ≥ 3 or discontinuation due to treatment-related adverse events (TRAEs). Hazard and risk ratios (HRs/RRs) were pooled using random-effects models (RStudio 2025.09.2 + 418).
Results
Eight RCTs (n = 3,978) were included. Overall, PFS did not differ significantly between groups (HR 0.80; 95 % CI 0.62–1.04; p = 0.09). Statistically significant PFS subgroups included: ESR1 mutation (HR 0.57; 95 % CI 0.45–0.73; p < 0.01); prior CDK4/6i use (HR 0.68; 95 % CI 0.49–0.95; p = 0.03); visceral metastases (HR 0.78; 95 % CI 0.63–0.97; p = 0.03); age < 65 years (HR 0.75; 95 % CI 0.60–0.92; p = 0.01); and oral SERDs versus fulvestrant (HR 0.55; 95 % CI 0.46–0.66; p < 0.01). Grade ≥ 3 TRAEs were higher with SERDs (RR 1.64; 95 % CI 1.07–2.50; p = 0.03), while treatment discontinuation was not significant.
Conclusions
Novel oral SERDs may represent a paradigm shift in managing PD after 1 L therapy, showing potential to improve PFS in selected patients.
背景：对于ER+/HER2 -转移性乳腺癌（mBC），牙髓素治疗（ET）加CDK4/6抑制剂（CDK4/6i）仍然是一线（1l）标准。然而，ESR1突变导致ET耐药和随后的疾病进展（PD）。肌注氟维司汀的局限性导致了新型口服选择性雌激素受体降解剂（serd）的发展。我们的目的是评估新型口服serd治疗ER+/HER2 - mBC的疗效和安全性。方法系统检索spubmed、Embase和Cochrane，检索比较口服serd与标准治疗的随机对照试验（rct）。主要结局是总体无进展生存期（PFS）和亚组（ESR1突变，绝经状态，年龄，既往CDK4/6i使用，内脏转移），ESR1突变患者口服serd与氟维司汀比较的PFS，以及分级≥3或因治疗相关不良事件（TRAEs）而停药。采用随机效应模型（RStudio 2025.09.2 + 418）汇总危险和风险比（hr /RRs）。结果共纳入8项rct （n = 3978）。总体而言，各组间PFS无显著差异（HR 0.80; 95% CI 0.62-1.04; p = 0.09）。具有统计学意义的PFS亚组包括：ESR1突变（HR 0.57; 95% CI 0.45-0.73; p < 0.01）；既往使用CDK4/6i (HR 0.68; 95% CI 0.49-0.95; p = 0.03)；内脏转移（HR 0.78; 95% CI 0.63-0.97; p = 0.03）；年龄& lt; 65年(HR 0.75; 95%可信区间0.60 - -0.92;p = 0.01);口服serd与氟维司汀比较（HR 0.55; 95% CI 0.46-0.66; p < 0.01）。≥3级trae与serd的相关性较高（RR 1.64; 95% CI 1.07-2.50; p = 0.03），而停药无统计学意义。结论：新型口服serd可能代表了1l治疗后PD治疗的范式转变，显示出改善特定患者PFS的潜力。
{"title":"Comparative efficacy and safety of novel oral selective estrogen receptor degraders in ER+/HER2– advanced breast cancer: An updated systematic review and meta-analysis of randomized controlled trials","authors":"Najwaa Kirmani , Nathalia De León-Fernández , Juan David Rodriguez-Parra , Laura Ghanem , Bezalel Hakkeem , Clara Briceño-Morales , Ximena Briceño-Morales","doi":"10.1016/j.ctrv.2026.103093","DOIUrl":"10.1016/j.ctrv.2026.103093","url":null,"abstract":"<div><h3>Background</h3><div>Endocrine therapy (ET) plus CDK4/6 inhibitors (CDK4/6i) remains first-line (1 L) standard for ER+/HER2– metastatic breast cancer (mBC). However, <em>ESR1</em> mutations lead to ET resistance and subsequent disease progression (PD). Limitations of intramuscular fulvestrant have led to the development of novel oral selective estrogen receptor degraders (SERDs). We aim to evaluate efficacy and safety of novel oral SERDs for ER+/HER2– mBC.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials (RCTs) comparing oral SERDs with standard treatment. Primary outcomes were progression-free survival (PFS) overall and by subgroups (<em>ESR1</em> mutation, menopausal status, age, prior CDK4/6i use, visceral metastases), PFS comparing oral SERDs versus fulvestrant in <em>ESR1</em>-mutated patients, and grade ≥ 3 or discontinuation due to treatment-related adverse events (TRAEs). Hazard and risk ratios (HRs/RRs) were pooled using random-effects models (RStudio 2025.09.2 + 418).</div></div><div><h3>Results</h3><div>Eight RCTs (n = 3,978) were included. Overall, PFS did not differ significantly between groups (HR 0.80; 95 % CI 0.62–1.04; <em>p = 0.09</em>). Statistically significant PFS subgroups included: <em>ESR1</em> mutation (HR 0.57; 95 % CI 0.45–0.73; <em>p < 0.01</em>); prior CDK4/6i use (HR 0.68; 95 % CI 0.49–0.95; <em>p = 0.03</em>); visceral metastases (HR 0.78; 95 % CI 0.63–0.97; <em>p = 0.03</em>); age < 65 years (HR 0.75; 95 % CI 0.60–0.92; <em>p = 0.01</em>); and oral SERDs versus fulvestrant (HR 0.55; 95 % CI 0.46–0.66; <em>p < 0.01</em>). Grade ≥ 3 TRAEs were higher with SERDs (RR 1.64; 95 % CI 1.07–2.50; <em>p = 0.03</em>), while treatment discontinuation was not significant.</div></div><div><h3>Conclusions</h3><div>Novel oral SERDs may represent a paradigm shift in managing PD after 1 L therapy, showing potential to improve PFS in selected patients.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103093"},"PeriodicalIF":10.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973594","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 : 2026-01-09DOI: 10.1016/j.ctrv.2026.103089
Clara Salva de Torres , Evelyn Elias , Caterina Vaghi , Nadia Saoudi González , Ariadna García , Adriana Alcaraz , Marta Rodríguez-Castells , Iosune Baraibar , Javier Ros , Francesc Salvà , Josep Tabernero , Elena Élez , Enrique Sanz-Garcia
Colorectal cancer (CRC) with mismatch-repair deficiency (dMMR) or high microsatellite instability (MSI-H) represents a distinct molecular subtype highly sensitive to immune checkpoint inhibitors (ICIs). Landmark clinical trials have established ICIs as standard-of-care in this setting, demonstrating durable responses and improved survival. However, up to one-third of patients will exhibit primary or acquired resistance, highlighting the urgent need for predictive biomarkers and novel therapeutic strategies. This review summarizes the clinical evidence supporting ICIs in dMMR/MSI-H CRC, explores mechanisms of resistance—including intrinsic and extrinsic modulators—and evaluates the role of potential predictive biomarkers of response. Finally, we discuss innovative therapeutic approaches to overcome resistance, including combination strategies, DNA repair pathway inhibitors, immune-oncology drugs beyond checkpoint inhibitors and microbiome-targeted interventions. Together, these insights aim to refine patient selection, optimize therapeutic benefit, and guide the development of next-generation therapies for dMMR/MSI-H CRC.
{"title":"Exploring resistance to immune checkpoints inhibitors in mismatch repair-deficient or microsatellite-instable colorectal cancer","authors":"Clara Salva de Torres , Evelyn Elias , Caterina Vaghi , Nadia Saoudi González , Ariadna García , Adriana Alcaraz , Marta Rodríguez-Castells , Iosune Baraibar , Javier Ros , Francesc Salvà , Josep Tabernero , Elena Élez , Enrique Sanz-Garcia","doi":"10.1016/j.ctrv.2026.103089","DOIUrl":"10.1016/j.ctrv.2026.103089","url":null,"abstract":"<div><div>Colorectal cancer (CRC) with mismatch-repair deficiency (dMMR) or high microsatellite instability (MSI-H) represents a distinct molecular subtype highly sensitive to immune checkpoint inhibitors (ICIs). Landmark clinical trials have established ICIs as standard-of-care in this setting, demonstrating durable responses and improved survival. However, up to one-third of patients will exhibit primary or acquired resistance, highlighting the urgent need for predictive biomarkers and novel therapeutic strategies. This review summarizes the clinical evidence supporting ICIs in dMMR/MSI-H CRC, explores mechanisms of resistance—including intrinsic and extrinsic modulators—and evaluates the role of potential predictive biomarkers of response. Finally, we discuss innovative therapeutic approaches to overcome resistance, including combination strategies, DNA repair pathway inhibitors, immune-oncology drugs beyond checkpoint inhibitors and microbiome-targeted interventions. Together, these insights aim to refine patient selection, optimize therapeutic benefit, and guide the development of next-generation therapies for dMMR/MSI-H CRC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103089"},"PeriodicalIF":10.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973678","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 : 2026-01-06DOI: 10.1016/j.ctrv.2025.103074
Kadriye Bir Yucel , Yusuf Ilhan , Elvina Almuradova , Murat Bardakci , Cigdem Dinckal , Yakup Ergun
Background
Human epidermal growth factor receptor 2 (HER2) overexpression defines a distinct breast cancer (BC) subtype that is highly sensitive to anti-HER2 therapy. However, the predictive and prognostic value of varying HER2 expression levels—specifically immunohistochemistry (IHC) 3 + versus IHC 2+/in situ hybridization (ISH)–positive—tumors remains uncertain. This systematic review and meta-analysis compared pathological complete response (pCR) between these subgroups in early-stage HER2-positive BC treated with anti-HER2–based neoadjuvant chemotherapy (NACT).
Methods
Following PRISMA guidelines (PROSPERO: CRD420251066320), PubMed, EMBASE, Cochrane Library, and ClinicalTrials databases were searched up to June 2025. Eligible studies compared HER2 (3 + ) and HER2 (2 + )/ISH + early-stage BC receiving anti-HER2–based NACT. Data extraction was performed independently by two reviewers. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated using fixed- or random-effects models according to heterogeneity.
Results
Thirteen retrospective studies involving 7,206 patients were included. Among 6,081 HER2-positive cases, 76 % were HER2 (3 + ) and 24 % were HER2 (2 + )/ISH + . The pooled pCR rate was significantly higher in HER2 (3 + ) tumors than in HER2 (2 + )/ISH + tumors (55.1 % vs. 21.6 %; OR = 5.38, 95 % CI: 3.72–7.80; p < 0.00001). The difference persisted in dual-targeted regimens (66.0 % vs. 32.9 %; OR = 4.31, 95 % CI: 2.70–6.88; p < 0.00001). No significant difference was observed in 3-year invasive disease-free survival (HR = 0.71, 95 % CI: 0.32–1.57; p = 0.40).
Conclusion
HER2 IHC 3 + tumors are substantially more likely to achieve pCR following anti-HER2–based NACT than HER2 (2 + )/ISH + tumors, indicating that HER2 expression intensity has predictive relevance. Quantitative HER2 assessment should be integrated into therapeutic planning and trial stratification to optimize outcomes in early-stage HER2-positive BC.
人表皮生长因子受体2 （HER2）过表达定义了一种独特的乳腺癌（BC）亚型，该亚型对抗HER2治疗高度敏感。然而，不同的HER2表达水平-特异性免疫组织化学（IHC） 3 +与IHC 2+/原位杂交（ISH）阳性肿瘤的预测和预后价值仍然不确定。本系统综述和荟萃分析比较了这些亚组在早期her2阳性BC中接受基于抗her2的新辅助化疗（NACT）治疗的病理完全缓解（pCR）。方法按照PRISMA指南（PROSPERO: CRD420251066320），检索截至2025年6月的PubMed、EMBASE、Cochrane Library和ClinicalTrials数据库。符合条件的研究比较了HER2（3 +）和HER2 (2 +)/ISH +早期BC接受基于抗HER2的NACT。数据提取由两名审稿人独立完成。根据异质性，采用固定效应或随机效应模型计算合并优势比（ORs）和风险比（hr）。结果纳入13项回顾性研究，涉及7206例患者。6081例HER2阳性病例中，76%为HER2(3 +)， 24%为HER2 (2 +)/ISH +。HER2（3 +）肿瘤的聚合pCR率明显高于HER2 (2 +)/ISH +肿瘤（55.1% vs. 21.6%; OR = 5.38, 95% CI: 3.72 ~ 7.80; p < 0.00001）。双靶向方案的差异仍然存在（66.0% vs. 32.9%; OR = 4.31, 95% CI: 2.70-6.88; p < 0.00001）。3年侵袭性无病生存率无统计学差异（HR = 0.71, 95% CI: 0.32-1.57; p = 0.40）。结论HER2 IHC 3 +肿瘤比HER2 (2 +)/ISH +肿瘤更有可能通过抗HER2 - based NACT实现pCR，表明HER2表达强度具有预测相关性。定量HER2评估应纳入治疗计划和试验分层，以优化早期HER2阳性BC的预后。
{"title":"Comparison of the pathological complete response between immunohistochemistry HER2 (3 + ) and HER2 (2 + )/ISH + Early-stage breast cancer: a systematic review and meta-analysis","authors":"Kadriye Bir Yucel , Yusuf Ilhan , Elvina Almuradova , Murat Bardakci , Cigdem Dinckal , Yakup Ergun","doi":"10.1016/j.ctrv.2025.103074","DOIUrl":"10.1016/j.ctrv.2025.103074","url":null,"abstract":"<div><h3>Background</h3><div>Human epidermal growth factor receptor 2 (HER2) overexpression defines a distinct breast cancer (BC) subtype that is highly sensitive to anti-HER2 therapy. However, the predictive and prognostic value of varying HER2 expression levels—specifically immunohistochemistry (IHC) 3 + versus IHC 2+/in situ hybridization (ISH)–positive—tumors remains uncertain. This systematic review and <em>meta</em>-analysis compared pathological complete response (pCR) between these subgroups in early-stage HER2-positive BC treated with anti-HER2–based neoadjuvant chemotherapy (NACT).</div></div><div><h3>Methods</h3><div>Following PRISMA guidelines (PROSPERO: CRD420251066320), PubMed, EMBASE, Cochrane Library, and ClinicalTrials databases were searched up to June 2025. Eligible studies compared HER2 (3 + ) and HER2 (2 + )/ISH + early-stage BC receiving anti-HER2–based NACT. Data extraction was performed independently by two reviewers. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated using fixed- or random-effects models according to heterogeneity.</div></div><div><h3>Results</h3><div>Thirteen retrospective studies involving 7,206 patients were included. Among 6,081 HER2-positive cases, 76 % were HER2 (3 + ) and 24 % were HER2 (2 + )/ISH + . The pooled pCR rate was significantly higher in HER2 (3 + ) tumors than in HER2 (2 + )/ISH + tumors (55.1 % vs. 21.6 %; OR = 5.38, 95 % CI: 3.72–7.80; p < 0.00001). The difference persisted in dual-targeted regimens (66.0 % vs. 32.9 %; OR = 4.31, 95 % CI: 2.70–6.88; p < 0.00001). No significant difference was observed in 3-year invasive disease-free survival (HR = 0.71, 95 % CI: 0.32–1.57; p = 0.40).</div></div><div><h3>Conclusion</h3><div>HER2 IHC 3 + tumors are substantially more likely to achieve pCR following anti-HER2–based NACT than HER2 (2 + )/ISH + tumors, indicating that HER2 expression intensity has predictive relevance. Quantitative HER2 assessment should be integrated into therapeutic planning and trial stratification to optimize outcomes in early-stage HER2-positive BC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103074"},"PeriodicalIF":10.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922951","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 : 2026-01-04DOI: 10.1016/j.ctrv.2025.103086
Chiara Fabbroni , Edward.W. Johnston , Roberta Sanfilippo , Dirk C. Strauss , Sylvie Bonvalot , Mateusz Spalek , Winan. J. Van Houdt , Samuel J. Ford , Kyo Won Lee , Abdulazeez Salawu , Carol J. Swallow , Susie Bae , David E. Gyorki , Chandrajit P. Raut , John E. Mullinax , Markus Albertsmeier , Ferdinando Cananzi , David Konieczkowski , Valerie P. Grignol , Elisabetta Pennacchioli , William W. Tseng
Background
Retroperitoneal sarcoma (RPS) encompasses a heterogenous group of rare malignancies that develop in the back of the abdomen. For localized primary disease, the mainstay of treatment is surgery. Beyond the primary site, patterns of disease manifestation vary by histologic type and include visceral organ metastasis, as well as intraabdominal multifocal disease. Although cure is extremely rare, some patients may still derive significant benefit from treatment.
Methods
A comprehensive literature search was performed and international, key opinion leaders for RPS met together to discuss principles of practice for multifocal and metastatic disease, summarized in 45 statements, each given a level of evidence and grade of recommendation.
Results
Patients should be evaluated in a multidisciplinary sarcoma center with experience in RPS and recognition of histologic type is critical to guide management. After pretreatment assessment that includes imaging and pathology review, the goals of treatment should be clarified upfront and aligned with the anticipated ability for the patient to tolerate treatment. Disease biology (e.g., disease-free interval) should be thoroughly understood. Treatment modalities can include a combination of surgery, non-surgical local therapy (radiation therapy, percutaneous tumor ablation and embolization) and systemic therapy.
Conclusions
This updated consensus document gives comprehensive and practical clinical guidance to providers for the management of multifocal and metastatic RPS. The current document also serves as the foundation for future clinical and translational investigation, as we continue to optimize patient care in these complex and challenging cases.
{"title":"Management of multifocal and metastatic retroperitoneal sarcoma: an updated consensus approach from the transatlantic retroperitoneal sarcoma working group (TARPSWG)","authors":"Chiara Fabbroni , Edward.W. Johnston , Roberta Sanfilippo , Dirk C. Strauss , Sylvie Bonvalot , Mateusz Spalek , Winan. J. Van Houdt , Samuel J. Ford , Kyo Won Lee , Abdulazeez Salawu , Carol J. Swallow , Susie Bae , David E. Gyorki , Chandrajit P. Raut , John E. Mullinax , Markus Albertsmeier , Ferdinando Cananzi , David Konieczkowski , Valerie P. Grignol , Elisabetta Pennacchioli , William W. Tseng","doi":"10.1016/j.ctrv.2025.103086","DOIUrl":"10.1016/j.ctrv.2025.103086","url":null,"abstract":"<div><h3>Background</h3><div>Retroperitoneal sarcoma (RPS) encompasses a heterogenous group of rare malignancies that develop in the back of the abdomen. For localized primary disease, the mainstay of treatment is surgery. Beyond the primary site, patterns of disease manifestation vary by histologic type and include visceral organ metastasis, as well as intraabdominal multifocal disease. Although cure is extremely rare, some patients may still derive significant benefit from treatment.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was performed and international, key opinion leaders for RPS met together to discuss principles of practice for multifocal and metastatic disease, summarized in 45 statements, each given a level of evidence and grade of recommendation.</div></div><div><h3>Results</h3><div>Patients should be evaluated in a multidisciplinary sarcoma center with experience in RPS and recognition of histologic type is critical to guide management. After pretreatment assessment that includes imaging and pathology review, the goals of treatment should be clarified upfront and aligned with the anticipated ability for the patient to tolerate treatment. Disease biology (e.g., disease-free interval) should be thoroughly understood. Treatment modalities can include a combination of surgery, non-surgical local therapy (radiation therapy, percutaneous tumor ablation and embolization) and systemic therapy.</div></div><div><h3>Conclusions</h3><div>This updated consensus document gives comprehensive and practical clinical guidance to providers for the management of multifocal and metastatic RPS. The current document also serves as the foundation for future clinical and translational investigation, as we continue to optimize patient care in these complex and challenging cases.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103086"},"PeriodicalIF":10.5,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922949","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 : 2026-01-03DOI: 10.1016/j.ctrv.2026.103087
Bartłomiej Skrzypiec, Agnieszka Żółciak-Siwińska, Lucyna Pietrzak, Krzysztof Bujko
Introduction
To enable cross-trial comparisons of the benefit-risk ratio of the watch-and- wait strategy, two endpoints are required: a primary to assess the benefit and a co-primary to assess the main risk, i.e. regrowth.
Material and methods
We performed a literature search to identify and critically analyse endpoints used to evaluate the watch-and-wait strategies.
Results and discussion
The review identified four watch-and-wait strategy-specific primary endpoints assessing benefit and four methods for calculating regrowth rate across nine prospective studies, indicating the need for standardisation. To initiate a debate on this topic, we discuss shortcomings of the following commonly used endpoints: 1) “The clinical complete response (cCR) rate” is flawed for demonstrating benefit, as it combines patients who ultimately achieve sustained cCR (‘winners’) with those who eventually experience regrowth (‘losers’); 2) “the organ preservation rate” combines two procedures with different outcomes: watch-and-wait strategy and local excision; 3) calculating “the regrowth rate” only among patients achieving cCR—while excluding those with near-cCR who pursue watch-and-wait but later require surgery for persistent or progressive abnormalities—leads to an underestimation of the risk associated with deferring surgery. The following endpoints do not share these limitations and are therefore proposed for consideration in the debate on standardisation: 1) proportion of patients with sustained cCR among those who start radio(chemo)therapy; 2) the calculation of regrowth rate among pooled patients with cCR and all with near-cCR pursuing watch-and-wait surveillance.
{"title":"Rethinking endpoints for the watch-and-wait strategy in rectal cancer","authors":"Bartłomiej Skrzypiec, Agnieszka Żółciak-Siwińska, Lucyna Pietrzak, Krzysztof Bujko","doi":"10.1016/j.ctrv.2026.103087","DOIUrl":"10.1016/j.ctrv.2026.103087","url":null,"abstract":"<div><h3>Introduction</h3><div>To enable cross-trial comparisons of the benefit-risk ratio of the watch-and- wait strategy, two endpoints are required: a primary to assess the benefit and a co-primary to assess the main risk, i.e. regrowth.</div></div><div><h3>Material and methods</h3><div>We performed a literature search to identify and critically analyse endpoints used to evaluate the watch-and-wait strategies.</div></div><div><h3>Results and discussion</h3><div>The review identified four watch-and-wait strategy-specific primary endpoints assessing benefit and four methods for calculating regrowth rate across nine prospective studies, indicating the need for standardisation. To initiate a debate on this topic, we discuss shortcomings of the following commonly used endpoints: 1) “The clinical complete response (cCR) rate” is flawed for demonstrating benefit, as it combines patients who ultimately achieve sustained cCR (‘winners’) with those who eventually experience regrowth (‘losers’); 2) “the organ preservation rate” combines two procedures with different outcomes: watch-and-wait strategy and local excision; 3) calculating “the regrowth rate” only among patients achieving cCR—while excluding those with near-cCR who pursue watch-and-wait but later require surgery for persistent or progressive abnormalities—leads to an underestimation of the risk associated with deferring surgery. The following endpoints do not share these limitations and are therefore proposed for consideration in the debate on standardisation: 1) proportion of patients with sustained cCR among those who start radio(chemo)therapy; 2) the calculation of regrowth rate among pooled patients with cCR and all with near-cCR pursuing watch-and-wait surveillance.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103087"},"PeriodicalIF":10.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919264","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}
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