Pub Date : 2024-10-11DOI: 10.1016/j.ctrv.2024.102840
Miaoying Cai , Yifu Wang , Huangrong Ma , Li Yang , Zhiyuan Xu
Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor of the head and neck, with approximately 70 % of patients being diagnosed at a locally advanced stage. Despite the responsiveness to radiotherapy and chemotherapy, the 5-year survival rate of locally advanced NPC (LANPC) remains at approximately 80 %. Hence, there is an urgent need for novel treatment strategies to improve the prognosis of patients with LANPC. Numerous studies have illustrated the efficacy of immune checkpoint inhibitors (ICIs) in recurrent/metastatic NPC. Hence, the potential of immunotherapy for LANPC is under investigation. Using the Web of Clinical Trials, we identified 84 relevant trials exploring immunotherapy for NPC, encompassing 17 trials focusing on ICIs for LANPC. Preliminary findings from several trials suggest that adding ICIs into the primary treatment for LANPC significantly enhances the objective response rate and progression-free survival, with manageable safety profiles. However, the type, dosage, and timing of integration (induction phase, concurrent phase, and adjuvant phase) of ICIs into standard primary treatment of LANPC varies among these trials and further researches are warranted. This review provides an overview of immunotherapy principles in NPC, discusses recent advances and challenges associated with ICIs in the primary treatment for LANPC derived from published and ongoing clinical trials, and outlines the current landscape of other immunotherapies in LANPC, such as adoptive cell therapy, immunomodulatory agents, and tumor vaccines in LANPC. These insights aim to inform clinical practice and guide future researches.
{"title":"Advances and challenges in immunotherapy for locally advanced nasopharyngeal carcinoma","authors":"Miaoying Cai , Yifu Wang , Huangrong Ma , Li Yang , Zhiyuan Xu","doi":"10.1016/j.ctrv.2024.102840","DOIUrl":"10.1016/j.ctrv.2024.102840","url":null,"abstract":"<div><div>Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor of the head and neck, with approximately 70 % of patients being diagnosed at a locally advanced stage. Despite the responsiveness to radiotherapy and chemotherapy, the 5-year survival rate of locally advanced NPC (LANPC) remains at approximately 80 %. Hence, there is an urgent need for novel treatment strategies to improve the prognosis of patients with LANPC. Numerous studies have illustrated the efficacy of immune checkpoint inhibitors (ICIs) in recurrent/metastatic NPC. Hence, the potential of immunotherapy for LANPC is under investigation. Using the Web of Clinical Trials, we identified 84 relevant trials exploring immunotherapy for NPC, encompassing 17 trials focusing on ICIs for LANPC. Preliminary findings from several trials suggest that adding ICIs into the primary treatment for LANPC significantly enhances the objective response rate and progression-free survival, with manageable safety profiles. However, the type, dosage, and timing of integration (induction phase, concurrent phase, and adjuvant phase) of ICIs into standard primary treatment of LANPC varies among these trials and further researches are warranted. This review provides an overview of immunotherapy principles in NPC, discusses recent advances and challenges associated with ICIs in the primary treatment for LANPC derived from published and ongoing clinical trials, and outlines the current landscape of other immunotherapies in LANPC, such as adoptive cell therapy, immunomodulatory agents, and tumor vaccines in LANPC. These insights aim to inform clinical practice and guide future researches.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"131 ","pages":"Article 102840"},"PeriodicalIF":9.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483073","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 : 2024-10-05DOI: 10.1016/j.ctrv.2024.102832
Stefania Gori , Fiorenza De Rose , Antonella Ferro , Alessandra Fabi , Catia Angiolini , Giuseppe Azzarello , Maurizio Cancian , Michela Cinquini , Luca Arecco , Cynthia Aristei , Daniela Bernardi , Laura Biganzoli , Anna Cariello , Laura Cortesi , Elisabetta Cretella , Carmen Criscitiello , Ugo De Giorgi , Maria Carmen De Santis , Giuseppe Deledda , Massimo Dessena , Alberto Zambelli
Breast cancer stands as the most frequently diagnosed cancer and the primary cause of cancer-related mortality among women worldwide, including Italy. With the increasing number of survivors, many are enrolled in regular follow-up programs. However, adherence to recommendations from scientific societies (such as ASCO, ESMO, AIOM) for breast cancer follow-up management varies in daily clinical practice across different cancer centers, potentially resulting in unequal management and escalating costs.
To address these concerns, the Italian Association of Multidisciplinary Oncology Groups (AIGOM) orchestrated a Consensus on early Breast Cancer follow-up utilizing the Estimate-Talk-Estimate methodology. Following the identification of 18 Items and 38 statements by a select Board, 46 out of 54 (85.1%) experts comprising a multidisciplinary and multiprofessional panel expressed their degree of consensus (Expert Panel).
The Expert Panel underscores the potential for the multidisciplinary team to tailor follow-up intensity based on the individual risk of recurrence. In selected cases, the general practitioner may be recommended as the clinical lead for breast cancer follow-up, both after completion of adjuvant treatment and at early initiation of endocrine therapy in low-risk patients. Throughout follow-up, and alongside oncologic surveillance, the expert panel advises osteometabolic, cardiologic, and gynecologic surveillance for the early detection and management of early and late treatment toxicities. Moreover, preserving quality of life is emphasized, with provisions for psycho-oncologic support and encouragement to adopt protective lifestyle behaviors.
{"title":"Follow-up of early breast cancer in a public health system: A 2024 AIGOM consensus project","authors":"Stefania Gori , Fiorenza De Rose , Antonella Ferro , Alessandra Fabi , Catia Angiolini , Giuseppe Azzarello , Maurizio Cancian , Michela Cinquini , Luca Arecco , Cynthia Aristei , Daniela Bernardi , Laura Biganzoli , Anna Cariello , Laura Cortesi , Elisabetta Cretella , Carmen Criscitiello , Ugo De Giorgi , Maria Carmen De Santis , Giuseppe Deledda , Massimo Dessena , Alberto Zambelli","doi":"10.1016/j.ctrv.2024.102832","DOIUrl":"10.1016/j.ctrv.2024.102832","url":null,"abstract":"<div><div>Breast cancer stands as the most frequently diagnosed cancer and the primary cause of cancer-related mortality among women worldwide, including Italy. With the increasing number of survivors, many are enrolled in regular follow-up programs. However, adherence to recommendations from scientific societies (such as ASCO, ESMO, AIOM) for breast cancer follow-up management varies in daily clinical practice across different cancer centers, potentially resulting in unequal management and escalating costs.</div><div>To address these concerns, the Italian Association of Multidisciplinary Oncology Groups (AIGOM) orchestrated a Consensus on early Breast Cancer follow-up utilizing the Estimate-Talk-Estimate methodology. Following the identification of 18 Items and 38 statements by a select Board, 46 out of 54 (85.1%) experts comprising a multidisciplinary and multiprofessional panel expressed their degree of consensus (Expert Panel).</div><div>The Expert Panel underscores the potential for the multidisciplinary team to tailor follow-up intensity based on the individual risk of recurrence. In selected cases, the general practitioner may be recommended as the clinical lead for breast cancer follow-up, both after completion of adjuvant treatment and at early initiation of endocrine therapy in low-risk patients. Throughout follow-up, and alongside oncologic surveillance, the expert panel advises osteometabolic, cardiologic, and gynecologic surveillance for the early detection and management of early and late treatment toxicities. Moreover, preserving quality of life is emphasized, with provisions for psycho-oncologic support and encouragement to adopt protective lifestyle behaviors.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"131 ","pages":"Article 102832"},"PeriodicalIF":9.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514605","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}
Neoadjuvant immune checkpoint blockade (ICB) combined with chemotherapy has improved survival outcomes in locally-advanced non-small cell lung cancer (NSCLC). However, its impact on surgery has not been fully elucidated. We performed a systematic review and meta-analysis to compare surgical outcomes between neoadjuvant chemoimmunotherapy and chemotherapy alone in resectable NSCLC. PubMed and Embase were searched to select randomized controlled trials (RCTs) evaluating neoadjuvant ICB therapy for resectable NSCLC. The risk difference (RD) and odds ratio (OR) of outcomes such as surgical and R0 resection rates, overall complication rates, treatment-related adverse events (TRAEs), and AEs leading to cancellation of surgery were pooled using the random-effect model meta-analysis. We also evaluated the correlations between overall survival (OS) and surgical and safety outcomes. Eight RCTs with 3,387 patients were analyzed. Neoadjuvant chemoimmunotherapy was associated with improved surgical resection (RD 4.52 %, 95 % confidence interval [CI] 0.95 %-8.09 %, p = 0.01) and R0 resection (RD 4.04 %, 95 % CI 1.69 %-6.40 %, p = 0.0008) without increasing overall complications (RD −0.13 %, 95 % CI −5.14 %-4.88 %, p = 0.96), but an increase in surgery cancellation due to AEs (RD 1.15 %, 95 % CI 0.25 %- 2.05 %; p = 0.01) and grade 3–4 TRAEs (RD 3.42 %, 95 % CI 0.33 %-6.52 %, p = 0.03). OS did not show a direct significant correlation with surgical outcomes or TRAEs. Neoadjuvant chemoimmunotherapy improves resection rates but increases high-grade TRAEs and AEs leading to surgery cancellation. Nevertheless, incorporating ICB into neoadjuvant approach appears reasonable by improving surgical outcomes, potentially leading to improved survival in patients with locally-advanced NSCLC.
{"title":"Surgical and safety outcomes in patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy versus chemotherapy alone: A systematic review and meta-analysis","authors":"Riona Aburaki , Yu Fujiwara , Kohei Chida , Nobuyuki Horita , Misako Nagasaka","doi":"10.1016/j.ctrv.2024.102833","DOIUrl":"10.1016/j.ctrv.2024.102833","url":null,"abstract":"<div><div>Neoadjuvant immune checkpoint blockade (ICB) combined with chemotherapy has improved survival outcomes in locally-advanced non-small cell lung cancer (NSCLC). However, its impact on surgery has not been fully elucidated. We performed a systematic review and <em>meta</em>-analysis to compare surgical outcomes between neoadjuvant chemoimmunotherapy and chemotherapy alone in resectable NSCLC. PubMed and Embase were searched to select randomized controlled trials (RCTs) evaluating neoadjuvant ICB therapy for resectable NSCLC. The risk difference (RD) and odds ratio (OR) of outcomes such as surgical and R0 resection rates, overall complication rates, treatment-related adverse events (TRAEs), and AEs leading to cancellation of surgery were pooled using the random-effect model <em>meta</em>-analysis. We also evaluated the correlations between overall survival (OS) and surgical and safety outcomes. Eight RCTs with 3,387 patients were analyzed. Neoadjuvant chemoimmunotherapy was associated with improved surgical resection (RD 4.52 %, 95 % confidence interval [CI] 0.95 %-8.09 %, p = 0.01) and R0 resection (RD 4.04 %, 95 % CI 1.69 %-6.40 %, p = 0.0008) without increasing overall complications (RD −0.13 %, 95 % CI −5.14 %-4.88 %, p = 0.96), but an increase in surgery cancellation due to AEs (RD 1.15 %, 95 % CI 0.25 %- 2.05 %; p = 0.01) and grade 3–4 TRAEs (RD 3.42 %, 95 % CI 0.33 %-6.52 %, p = 0.03). OS did not show a direct significant correlation with surgical outcomes or TRAEs. Neoadjuvant chemoimmunotherapy improves resection rates but increases high-grade TRAEs and AEs leading to surgery cancellation. Nevertheless, incorporating ICB into neoadjuvant approach appears reasonable by improving surgical outcomes, potentially leading to improved survival in patients with locally-advanced NSCLC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"131 ","pages":"Article 102833"},"PeriodicalIF":9.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382759","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 : 2024-09-24DOI: 10.1016/j.ctrv.2024.102830
Ye Lu , Xiangyi Kong , Xiangyu Wang , Wenxiang Zhang , Yifei Li , Hao Dong , Zhongzhao Wang , Jidong Gao , Jing Wang
Primary acinic cell carcinoma (PACC) of the breast is a rare oncological entity that mimics acinar cell differentiation similar to that observed in salivary glands. This distinct subtype is characterized by low-grade malignancy and has only been documented in a limited number of cases. Despite its classification frequently as TNBC, PACC of the breast typically shows a comparatively favorable prognosis. Our study aims to enrich the current understanding of PACC through a comprehensive review of cases managed at our institution, analyzing their clinical, histopathological, and therapeutic profiles including chemotherapy and radiation therapy, and patient outcomes and allows us to compile a comprehensive dataset for in-depth analysis of treatment responses and long-term survival rates, contributing to a broader understanding of the disease’s natural history.
{"title":"Deciphering primary acinic cell carcinoma of the Breast: Insights from a comprehensive case series and Systematic review","authors":"Ye Lu , Xiangyi Kong , Xiangyu Wang , Wenxiang Zhang , Yifei Li , Hao Dong , Zhongzhao Wang , Jidong Gao , Jing Wang","doi":"10.1016/j.ctrv.2024.102830","DOIUrl":"10.1016/j.ctrv.2024.102830","url":null,"abstract":"<div><div>Primary acinic cell carcinoma (PACC) of the breast is a rare oncological entity that mimics acinar cell differentiation similar to that observed in salivary glands. This distinct subtype is characterized by low-grade malignancy and has only been documented in a limited number of cases. Despite its classification frequently as TNBC, PACC of the breast typically shows a comparatively favorable prognosis. Our study aims to enrich the current understanding of PACC through a comprehensive review of cases managed at our institution, analyzing their clinical, histopathological, and therapeutic profiles including chemotherapy and radiation therapy, and patient outcomes and allows us to compile a comprehensive dataset for in-depth analysis of treatment responses and long-term survival rates, contributing to a broader understanding of the disease’s natural history.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"131 ","pages":"Article 102830"},"PeriodicalIF":9.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441503","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 : 2024-09-24DOI: 10.1016/j.ctrv.2024.102831
Federico Rebaudi , Fabiana De Franco , Rayan Goda , Valentina Obino , Giorgio Vita , Camilla Baronti , Eleonora Iannone , Francesca Pitto , Barbara Massa , Daniela Fenoglio , Camilla Jandus , Francesca Poggio , Piero Fregatti , Ombretta Melaiu , Matteo Bozzo , Simona Candiani , Federica Papaccio , Marco Greppi , Silvia Pesce , Emanuela Marcenaro
This review focuses on the immune checkpoint inhibitors (ICIs) in the context of breast cancer (BC) management. These innovative treatments, by targeting proteins expressed on both tumor and immune cells, aim to overcome tumor-induced immune suppression and reactivate the immune system. The potential of this approach is the subject of numerous clinical studies. Here, we explore the key studies and emerging therapies related to ICIs providing a detailed analysis of their specific and combined use in BC treatment.
{"title":"The landscape of combining immune checkpoint inhibitors with novel Therapies: Secret alliances against breast cancer","authors":"Federico Rebaudi , Fabiana De Franco , Rayan Goda , Valentina Obino , Giorgio Vita , Camilla Baronti , Eleonora Iannone , Francesca Pitto , Barbara Massa , Daniela Fenoglio , Camilla Jandus , Francesca Poggio , Piero Fregatti , Ombretta Melaiu , Matteo Bozzo , Simona Candiani , Federica Papaccio , Marco Greppi , Silvia Pesce , Emanuela Marcenaro","doi":"10.1016/j.ctrv.2024.102831","DOIUrl":"10.1016/j.ctrv.2024.102831","url":null,"abstract":"<div><div>This review focuses on the immune checkpoint inhibitors (ICIs) in the context of breast cancer (BC) management. These innovative treatments, by targeting proteins expressed on both tumor and immune cells, aim to overcome tumor-induced immune suppression and reactivate the immune system. The potential of this approach is the subject of numerous clinical studies. Here, we explore the key studies and emerging therapies related to ICIs providing a detailed analysis of their specific and combined use in BC treatment.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"130 ","pages":"Article 102831"},"PeriodicalIF":9.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334356","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 : 2024-09-16DOI: 10.1016/j.ctrv.2024.102829
Roberto Moretto , Guglielmo Vetere , Martina Carullo , Paolo Ciracì , Gianluca Masi , Chiara Cremolini
<div><h3>Background</h3><p>The PRODIGE-23 study showed a higher benefit for FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) as induction chemotherapy followed by long-course chemoradiotherapy (CTRT) respect to neoadjuvant CTRT alone both followed by total mesorectal excision (TME) in terms of disease-free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The added value of treatment intensification with irinotecan, over the doublet induction with fluoropyrimidine and oxaliplatin is still debated.</p></div><div><h3>Objective</h3><p>To assess survival, pathological complete response (pCR) rate, and safety from phase II-III trials comparing triplet and doublet induction both followed by CTRT and TME in LARC.</p></div><div><h3>Methods</h3><p>After a systematic literature review of PubMed, Embase, Cochrane, American Society of Clinical Oncology and European Society for Medical Oncology meetings’ libraries, data from Kaplan-Meier (KM) curves were extracted from phase II-III clinical trials. Phase II-III trials including at least one treatment arm with doublet or triplet induction chemotherapy without biological agents administered for a minimum of 3 months followed by long-course CTRT and TME and with at least 48 months of follow-up were selected. When available, the neoadjuvant CTRT alone arms of the selected studies were included as a comparator reference treatment. Individual patient DFS and OS data were extracted from Kaplan-Meier plots of original trials through graphical reconstruction between April 10th and May 19th, 2024. A pooled analysis was conducted, and results were validated in a subsequent network <em>meta</em>-analysis (NMA). pCR rates and grade ≥ 3 adverse events rates were also collected. Primary endpoints were DFS and OS between triplet and doublet induction. Secondary endpoints were DFS and OS between neoadjuvant CTRT alone and triplet or doublet induction as well as pCR rates and safety profile among different arms.</p></div><div><h3>Results</h3><p>Out of 674 patients enrolled in 3 trials, 231, 161 and 282 were treated with FOLFIRINOX or CAPOX (capecitabine and oxaliplatin) followed by CTRT or neoadjuvant CTRT alone, respectively. 5-year DFS rates were 73.1 % [95 %CI: 67.2 % – 79.0 %], 61.7 % [95 %CI: 53.9 % – 69.5 %] and 65.1 % [95 %CI: 59.4 % – 70.8 %] for triplet induction, doublet induction, and neoadjuvant CTRT alone, respectively. 5-year OS rates were 86.8 % [95 %CI: 82.3 % – 91.3 %], 74.7 % [95 %CI: 67.6 % – 81.8 %], and 79.6 % [95 %CI: 74.9 % – 84.3 %] for FOLFIRINOX, CAPOX, and neoadjuvant CTRT alone, respectively. Triplet induction showed longer DFS and OS respect to doublet induction (HR for DFS: 0.67 [95 % CI 0.47 – 0.96], p = 0.03; HR for OS: 0.49 [95 % CI 0.31 – 0.78], p = 0.003) with a trend for superiority when compared with neoadjuvant CTRT alone (HR for DFS: 0.77 [95 % CI 0.57 – 1.05], p = 0.10; HR for OS: 0.67 [95 % CI 0.45 – 1.01], p = 0.06). No difference was observed be
{"title":"Induction treatment with FOLFIRINOX or oxaliplatin-based doublet followed by long-course chemoradiotherapy and surgery in locally advanced rectal cancer. A systematic review and pooled analysis from phase II and III trials.","authors":"Roberto Moretto , Guglielmo Vetere , Martina Carullo , Paolo Ciracì , Gianluca Masi , Chiara Cremolini","doi":"10.1016/j.ctrv.2024.102829","DOIUrl":"10.1016/j.ctrv.2024.102829","url":null,"abstract":"<div><h3>Background</h3><p>The PRODIGE-23 study showed a higher benefit for FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) as induction chemotherapy followed by long-course chemoradiotherapy (CTRT) respect to neoadjuvant CTRT alone both followed by total mesorectal excision (TME) in terms of disease-free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The added value of treatment intensification with irinotecan, over the doublet induction with fluoropyrimidine and oxaliplatin is still debated.</p></div><div><h3>Objective</h3><p>To assess survival, pathological complete response (pCR) rate, and safety from phase II-III trials comparing triplet and doublet induction both followed by CTRT and TME in LARC.</p></div><div><h3>Methods</h3><p>After a systematic literature review of PubMed, Embase, Cochrane, American Society of Clinical Oncology and European Society for Medical Oncology meetings’ libraries, data from Kaplan-Meier (KM) curves were extracted from phase II-III clinical trials. Phase II-III trials including at least one treatment arm with doublet or triplet induction chemotherapy without biological agents administered for a minimum of 3 months followed by long-course CTRT and TME and with at least 48 months of follow-up were selected. When available, the neoadjuvant CTRT alone arms of the selected studies were included as a comparator reference treatment. Individual patient DFS and OS data were extracted from Kaplan-Meier plots of original trials through graphical reconstruction between April 10th and May 19th, 2024. A pooled analysis was conducted, and results were validated in a subsequent network <em>meta</em>-analysis (NMA). pCR rates and grade ≥ 3 adverse events rates were also collected. Primary endpoints were DFS and OS between triplet and doublet induction. Secondary endpoints were DFS and OS between neoadjuvant CTRT alone and triplet or doublet induction as well as pCR rates and safety profile among different arms.</p></div><div><h3>Results</h3><p>Out of 674 patients enrolled in 3 trials, 231, 161 and 282 were treated with FOLFIRINOX or CAPOX (capecitabine and oxaliplatin) followed by CTRT or neoadjuvant CTRT alone, respectively. 5-year DFS rates were 73.1 % [95 %CI: 67.2 % – 79.0 %], 61.7 % [95 %CI: 53.9 % – 69.5 %] and 65.1 % [95 %CI: 59.4 % – 70.8 %] for triplet induction, doublet induction, and neoadjuvant CTRT alone, respectively. 5-year OS rates were 86.8 % [95 %CI: 82.3 % – 91.3 %], 74.7 % [95 %CI: 67.6 % – 81.8 %], and 79.6 % [95 %CI: 74.9 % – 84.3 %] for FOLFIRINOX, CAPOX, and neoadjuvant CTRT alone, respectively. Triplet induction showed longer DFS and OS respect to doublet induction (HR for DFS: 0.67 [95 % CI 0.47 – 0.96], p = 0.03; HR for OS: 0.49 [95 % CI 0.31 – 0.78], p = 0.003) with a trend for superiority when compared with neoadjuvant CTRT alone (HR for DFS: 0.77 [95 % CI 0.57 – 1.05], p = 0.10; HR for OS: 0.67 [95 % CI 0.45 – 1.01], p = 0.06). No difference was observed be","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"130 ","pages":"Article 102829"},"PeriodicalIF":9.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224001579/pdfft?md5=731879fc941d5c6224ec67a08070c094&pid=1-s2.0-S0305737224001579-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270577","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 : 2024-09-11DOI: 10.1016/j.ctrv.2024.102825
Mathilde Gheysen , Kevin Punie , Hans Wildiers , Patrick Neven
Background
Primary and acquired endocrine resistance remains a major issue in the treatment of hormone receptor positive breast cancer. Acquired resistance often results from estrogen receptor 1 (ESR1) mutations leading to estrogen independent estrogen receptor activation. Selective estrogen receptor degraders (SERDs) induce degradation of this receptor, thereby overcoming this resistance. The intramuscular administration and modest efficacy of fulvestrant, the first SERD, triggered development of oral, more potent SERDs. This narrative review gives an overview of the current evidence regarding this new drug class.
Methods
Medline/PubMed and Embase database were screened using a systematic search strategy. We assessed the San Antonio Breast Cancer Symposium abstract reports, the European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) meeting resources by applying the following terms: ‘SERD’, ‘giredestrant’, ‘elacestrant’, ‘imlunestrant’, ‘amcenestrant’, ‘camizestrant’ and ‘rintodestrant’. ClinicalTrials.gov was consulted to include ongoing trials.
Results
The search retrieved 1191 articles. After screening, 108 articles were retained. In the phase 3 EMERALD trial, elacestrant demonstrated benefit in progression free survival (PFS) in second line metastatic disease in postmenopausal women or men, leading to Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for the ESR1 mutated population. This PFS advantage was more pronounced among patients who had priorly received at least 12 months of a cyclin-dependent kinases 4/6 inhibitor (CDK4/6i). In the phase 2 SERENA-2 trial, camizestrant improved PFS as second line treatment. However, trials of giredestrant and amcenestrant failed to show PFS benefit in second line metastatic setting. In the preoperative setting, several oral SERDs resulted in a significant reduction of tumoral proliferation. Furthermore, many trials are still in progress.
Conclusion
Oral SERDs constitute an exciting new drug class. Ongoing and future research will further refine the role of these drugs next to standard endocrine treatments and targeted therapies.
{"title":"Oral SERDs changing the scenery in hormone receptor positive breast cancer, a comprehensive review","authors":"Mathilde Gheysen , Kevin Punie , Hans Wildiers , Patrick Neven","doi":"10.1016/j.ctrv.2024.102825","DOIUrl":"10.1016/j.ctrv.2024.102825","url":null,"abstract":"<div><h3>Background</h3><p>Primary and acquired endocrine resistance remains a major issue in the treatment of hormone receptor positive breast cancer. Acquired resistance often results from estrogen receptor 1 (<em>ESR1</em>) mutations leading to estrogen independent estrogen receptor activation. Selective estrogen receptor degraders (SERDs) induce degradation of this receptor, thereby overcoming this resistance. The intramuscular administration and modest efficacy of fulvestrant, the first SERD, triggered development of oral, more potent SERDs. This narrative review gives an overview of the current evidence regarding this new drug class.</p></div><div><h3>Methods</h3><p>Medline/PubMed and Embase database were screened using a systematic search strategy. We assessed the San Antonio Breast Cancer Symposium abstract reports, the European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) meeting resources by applying the following terms: ‘SERD’, ‘giredestrant’, ‘elacestrant’, ‘imlunestrant’, ‘amcenestrant’, ‘camizestrant’ and ‘rintodestrant’. ClinicalTrials.gov was consulted to include ongoing trials.</p></div><div><h3>Results</h3><p>The search retrieved 1191 articles. After screening, 108 articles were retained. In the phase 3 EMERALD trial, elacestrant demonstrated benefit in progression free survival (PFS) in second line metastatic disease in postmenopausal women or men, leading to Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for the <em>ESR1</em> mutated population. This PFS advantage was more pronounced among patients who had priorly received at least 12 months of a cyclin-dependent kinases 4/6 inhibitor (CDK4/6i). In the phase 2 SERENA-2 trial, camizestrant improved PFS as second line treatment. However, trials of giredestrant and amcenestrant failed to show PFS benefit in second line metastatic setting. In the preoperative setting, several oral SERDs resulted in a significant reduction of tumoral proliferation. Furthermore, many trials are still in progress.</p></div><div><h3>Conclusion</h3><p>Oral SERDs constitute an exciting new drug class. Ongoing and future research will further refine the role of these drugs next to standard endocrine treatments and targeted therapies.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"130 ","pages":"Article 102825"},"PeriodicalIF":9.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224001531/pdfft?md5=8421fea5bbb25d737f5e4ddb8c86757b&pid=1-s2.0-S0305737224001531-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238113","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}
With the advancements in conventional treatment modalities such as radiation, chemotherapy, and surgery, as well as the emergence of immunotherapy, the overall cure rate for solid tumor malignancies has experienced a significant increase. However, it is unfortunate that exposure to cancer treatments can have detrimental effects on the function of osteoblasts and osteoclasts, disturbing bone metabolic homeostasis in patients, as well as causing damage to bone marrow cells and other bone tissues. Consequently, certain tumor treatment options may pose a risk for subsequent bone diseases. Common bone disorders associated with cancer treatment include osteonecrosis, bone loss, and secondary bone tumors. (1)Cancer treatment-related osteonecrosis is primarily linked to the use of radiation therapy and certain chemicals, such as bisphosphonates, denosumab, antiangiogenic agents, and immunomodulators. It has been observed that high-dose radiation therapy is more likely to result in osteonecrosis. (2)Chemicals and hormones, particularly sex hormones, glucocorticoids, and thyroid hormones or thyrotropic hormones, are among the factors that can contribute to cancer treatment-related bone loss. (3)Secondary bone tumors differ from metastases originating from primary tumors, and radiotherapy plays a significant role in their development, while chemotherapy may also exert some influence. Radiogenic secondary bone tumors are predominantly malignant, with osteosarcoma being the most common type. Chemotherapy may be a risk factor for the relatively rare occurrence of secondary Ewing sarcoma of the bone. These treatment-related bone disorders have a considerable adverse impact on the prognosis of cancer patients. Hence, it is imperative to prioritize the bone health of patients undergoing cancer treatment and give it further attention.
{"title":"Bone complications of cancer treatment","authors":"Nanxi Zhu , Hao Ni , Shengzhao Guo, Ying-Qiang Shen, Qianming Chen","doi":"10.1016/j.ctrv.2024.102828","DOIUrl":"10.1016/j.ctrv.2024.102828","url":null,"abstract":"<div><p>With the advancements in conventional treatment modalities such as radiation, chemotherapy, and surgery, as well as the emergence of immunotherapy, the overall cure rate for solid tumor malignancies has experienced a significant increase. However, it is unfortunate that exposure to cancer treatments can have detrimental effects on the function of osteoblasts and osteoclasts, disturbing bone metabolic homeostasis in patients, as well as causing damage to bone marrow cells and other bone tissues. Consequently, certain tumor treatment options may pose a risk for subsequent bone diseases. Common bone disorders associated with cancer treatment include osteonecrosis, bone loss, and secondary bone tumors. (1)Cancer treatment-related osteonecrosis is primarily linked to the use of radiation therapy and certain chemicals, such as bisphosphonates, denosumab, antiangiogenic agents, and immunomodulators. It has been observed that high-dose radiation therapy is more likely to result in osteonecrosis. (2)Chemicals and hormones, particularly sex hormones, glucocorticoids, and thyroid hormones or thyrotropic hormones, are among the factors that can contribute to cancer treatment-related bone loss. (3)Secondary bone tumors differ from metastases originating from primary tumors, and radiotherapy plays a significant role in their development, while chemotherapy may also exert some influence. Radiogenic secondary bone tumors are predominantly malignant, with osteosarcoma being the most common type. Chemotherapy may be a risk factor for the relatively rare occurrence of secondary Ewing sarcoma of the bone. These treatment-related bone disorders have a considerable adverse impact on the prognosis of cancer patients. Hence, it is imperative to prioritize the bone health of patients undergoing cancer treatment and give it further attention.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"130 ","pages":"Article 102828"},"PeriodicalIF":9.6,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224001567/pdfft?md5=e887f00481c06a323976a8760da64f90&pid=1-s2.0-S0305737224001567-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173534","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}
Recently, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have emerged as a novel treatment strategy for breast cancer. However, increasing reports of CDK4/6i-associated venous thromboembolism (VTE) have garnered attention. This study assessed CDK4/6i-associated VTE in breast cancer, and examined the effect of CDK4/6i on platelet/coagulation function for the first time in vitro.
Methods
PubMed and Embase databases were searched for studies published from the establishment of the database to December 31, 2022 for randomized controlled trials (RCTs) and real-world studies of CDK4/6i in patients with breast cancer, and the data obtained from the included studies were used for meta-analysis. A disproportionality analysis by extracting adverse drug reaction signals of CDK4/6i-associated VTE from the FDA Adverse Event Reporting System (FAERS) database was also conducted. Additionally, the in vitro effect of CDK4/6i on platelet function was assessed based on platelet aggregation tests and flow cytometry, and coagulation function was assessed based on the blood clotting function test.
Findings
A total of 16,903 patients in 13 RCTs and 6,490 patients in 9 real-world studies were included in the meta-analysis. In RCTs, VTE occurred in 193 (2.1 %) and 55 (0.7 %) patients in the CDK4/6i and control groups, respectively. In real-world studies, the aggregate incidence rate of VTE was 4.2 % (95 % CI: 2.1, 6.3). The meta-analysis of RCTs revealed that abemaciclib (Odds ratio [OR]: 4.40 [95 % CI: 2.74,7.05], p < 0.001) and palbociclib (OR: 2.35 [95 % CI: 1.34, 4.12], p < 0.01) significantly increased the risk of VTE in patients with breast cancer compared to placebo. FAERS database analysis revealed that abemaciclib (reporting odds ratio [ROR]: 1.63 [95 % CI: 1.36, 1.97]; IC025: 0.67) and ribociclib (ROR: 1.17 [95 % CI: 1.0, 1.39]; IC025: 0.18) demonstrated a significantly increased signal of VTE. Similarly, findings from in vitro experiments demonstrated that abemaciclib enhanced agonist-induced platelet activation, especially when collagen was used as the inducer, and this effect became more prominent with increasing its concentration.
Interpretation
Use of abemaciclib may increase the risk of VTE in patients with breast cancer, which may be partially attributed to the effect of abemaciclib on platelet function. Close monitoring of VTE occurrence is highly recommended while using abemaciclib, especially in patients at a high risk of VTE.
{"title":"Abemaciclib increases the risk of venous thromboembolism in breast cancer: Integrate meta-analysis, pharmacovigilance database analysis, and in vitro validation","authors":"Manqi Hua , Fei Xiong , Shan Chong , Zhuo Zhang , Qianxin Liu , Jingyi Hou , Zhiqi Zhang , Zhichun Gu , Xiangli Cui , Yimin Cui , Ling Xu , Qian Xiang","doi":"10.1016/j.ctrv.2024.102827","DOIUrl":"10.1016/j.ctrv.2024.102827","url":null,"abstract":"<div><h3>Background</h3><p>Recently, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have emerged as a novel treatment strategy for breast cancer. However, increasing reports of CDK4/6i-associated venous thromboembolism (VTE) have garnered attention. This study assessed CDK4/6i-associated VTE in breast cancer, and examined the effect of CDK4/6i on platelet/coagulation function for the first time <em>in vitro</em>.</p></div><div><h3>Methods</h3><p>PubMed and Embase databases were searched for studies published from the establishment of the database to December 31, 2022 for randomized controlled trials (RCTs) and real-world studies of CDK4/6i in patients with breast cancer, and the data obtained from the included studies were used for <em>meta</em>-analysis. A disproportionality analysis by extracting adverse drug reaction signals of CDK4/6i-associated VTE from the FDA Adverse Event Reporting System (FAERS) database was also conducted. Additionally, the <em>in vitro</em> effect of CDK4/6i on platelet function was assessed based on platelet aggregation tests and flow cytometry, and coagulation function was assessed based on the blood clotting function test.</p></div><div><h3>Findings</h3><p>A total of 16,903 patients in 13 RCTs and 6,490 patients in 9 real-world studies were included in the <em>meta</em>-analysis. In RCTs, VTE occurred in 193 (2.1 %) and 55 (0.7 %) patients in the CDK4/6i and control groups, respectively. In real-world studies, the aggregate incidence rate of VTE was 4.2 % (95 % CI: 2.1, 6.3). The <em>meta</em>-analysis of RCTs revealed that abemaciclib (Odds ratio [OR]: 4.40 [95 % CI: 2.74,7.05], p < 0.001) and palbociclib (OR: 2.35 [95 % CI: 1.34, 4.12], p < 0.01) significantly increased the risk of VTE in patients with breast cancer compared to placebo. FAERS database analysis revealed that abemaciclib (reporting odds ratio [ROR]: 1.63 [95 % CI: 1.36, 1.97]; IC<sub>025</sub>: 0.67) and ribociclib (ROR: 1.17 [95 % CI: 1.0, 1.39]; IC<sub>025</sub>: 0.18) demonstrated a significantly increased signal of VTE. Similarly, findings from <em>in vitro</em> experiments demonstrated that abemaciclib enhanced agonist-induced platelet activation, especially when collagen was used as the inducer, and this effect became more prominent with increasing its concentration.</p></div><div><h3>Interpretation</h3><p>Use of abemaciclib may increase the risk of VTE in patients with breast cancer, which may be partially attributed to the effect of abemaciclib on platelet function. Close monitoring of VTE occurrence is highly recommended while using abemaciclib, especially in patients at a high risk of VTE.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"130 ","pages":"Article 102827"},"PeriodicalIF":9.6,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224001555/pdfft?md5=900de26a15033f6cea82b631e4857ea1&pid=1-s2.0-S0305737224001555-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232926","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 : 2024-09-04DOI: 10.1016/j.ctrv.2024.102824
Carla Corvaja, Antonio Passaro, Ilaria Attili, Pamela Trillo Aliaga, Gianluca Spitaleri, Ester Del Signore, Filippo de Marinis
Third-generation EGFR tyrosine kinase inhibitor (TKIs) have revolutionized the treatment landscape for patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations, with improved long-term outcomes compared to first-generation TKIs. Nevertheless, disease progression inevitably occurs, limiting osimertinib long-term efficacy. Indeed, the molecular biology underlying acquired resistance to first-line osimertinib is multifaceted and includes the emergence of on-target and off-target alterations. EGFR-C797S mutation represents the most frequent mechanism of on-target resistance and hinders drug binding to the target site. EGFR-independent resistance includes the activation of alternative signaling pathways, such as MET amplification and HER2 mutations, and histological transformation. In this setting, chemotherapy is the current therapeutic option, with modest clinical outcomes. Therefore, the development of novel therapeutic strategies to overcome resistance to osimertinib is a major challenge. In this setting, fourth-generation TKIs are emerging as an interesting therapeutic option to overcome on-target resistance. Preclinical drug development has led to the discovery of thiazole-amid inhibitors, which activity is mediated by the allosteric inhibition of EGFR, resulting in high specificity towards mutant-EGFR. Early phase 1/2 clinical trials are ongoing to elucidate their activity also in the clinical setting. Aim of this review is to provide a state-of-the-art analysis on preclinical development of fourth-generation EGFR-TKIs and promising preliminary clinical data.
{"title":"Advancements in fourth-generation EGFR TKIs in EGFR-mutant NSCLC: Bridging biological insights and therapeutic development","authors":"Carla Corvaja, Antonio Passaro, Ilaria Attili, Pamela Trillo Aliaga, Gianluca Spitaleri, Ester Del Signore, Filippo de Marinis","doi":"10.1016/j.ctrv.2024.102824","DOIUrl":"10.1016/j.ctrv.2024.102824","url":null,"abstract":"<div><div>Third-generation EGFR tyrosine kinase inhibitor (TKIs) have revolutionized the treatment landscape for patients with non-small cell lung cancer (NSCLC) harboring <em>EGFR</em> activating mutations, with improved long-term outcomes compared to first-generation TKIs. Nevertheless, disease progression inevitably occurs, limiting osimertinib long-term efficacy. Indeed, the molecular biology underlying acquired resistance to first-line osimertinib is multifaceted and includes the emergence of on-target and off-target alterations. <em>EGFR</em>-C797S mutation represents the most frequent mechanism of on-target resistance and hinders drug binding to the target site. <em>EGFR</em>-independent resistance includes the activation of alternative signaling pathways, such as <em>MET</em> amplification and <em>HER2</em> mutations, and histological transformation. In this setting, chemotherapy is the current therapeutic option, with modest clinical outcomes. Therefore, the development of novel therapeutic strategies to overcome resistance to osimertinib is a major challenge. In this setting, fourth-generation TKIs are emerging as an interesting therapeutic option to overcome on-target resistance. Preclinical drug development has led to the discovery of thiazole-amid inhibitors, which activity is mediated by the allosteric inhibition of EGFR, resulting in high specificity towards mutant-EGFR. Early phase 1/2 clinical trials are ongoing to elucidate their activity also in the clinical setting. Aim of this review is to provide a state-of-the-art analysis on preclinical development of fourth-generation EGFR-TKIs and promising preliminary clinical data.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"130 ","pages":"Article 102824"},"PeriodicalIF":9.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376459","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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