Francesco Panzuto , Simona Barbi , Annalisa Trama , Nicola Fazio
{"title":"The importance of education and training in neuroendocrine neoplasms: challenges and opportunities for multidisciplinary management","authors":"Francesco Panzuto , Simona Barbi , Annalisa Trama , Nicola Fazio","doi":"10.1016/j.ctrv.2025.102998","DOIUrl":"10.1016/j.ctrv.2025.102998","url":null,"abstract":"<div><div>Neuroendocrine neoplasms (NENs) exemplify the challenges and opportunities inherent in managing rare cancers. Their rarity, biological heterogeneity, and diagnostic complexity necessitate a highly structured and multidisciplinary approach to patient care. In this context, education and training emerge as central pillars for improving clinical outcomes.</div><div>This review highlights how integrating multidisciplinary teams of diverse medical specialties enhances diagnostic accuracy, refines therapeutic strategies, and ensures adherence to evolving best practices. Establishing dedicated training pathways—both through traditional educational models and innovative digital platforms—is crucial to address the unique learning needs posed by NENs.</div><div>Scientific societies play a pivotal role by producing guidelines and fostering continuous professional development, although notable variability across international recommendations emphasizes the need for clinicians to harmonize and interpret critically. Patient advocacy groups, meanwhile, have become essential actors in the educational ecosystem, bridging informational gaps and advocating for patient-centered research and policy initiatives.</div><div>Emerging technologies, particularly artificial intelligence, offer promising tools to support clinical education and decision-making, provided that their implementation is cautious, validated, and integrated under healthcare professionals’ guidance.</div><div>By analyzing the NEN model, this review underscores that the future of rare cancer management relies on building strong collaborative networks, promoting standardized yet flexible educational programs, and embracing technological innovation, always focusing on quality, safety, and patient-centered care.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102998"},"PeriodicalIF":9.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703596","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}
Anja Holz , Bidisha Paul , Antonia Zapf , Klaus Pantel , Simon A. Joosse
{"title":"Circulating tumor DNA as prognostic marker in patients with metastatic colorectal cancer undergoing systemic therapy: A systematic review and meta-analysis","authors":"Anja Holz , Bidisha Paul , Antonia Zapf , Klaus Pantel , Simon A. Joosse","doi":"10.1016/j.ctrv.2025.102999","DOIUrl":"10.1016/j.ctrv.2025.102999","url":null,"abstract":"<div><h3>Background</h3><div>The response to systemic therapy against metastatic colorectal cancer (mCRC) is currently assessed by radiologic imaging. However, an increasing number of studies have shown that circulating tumor DNA (ctDNA) as liquid biopsy can be used as an alternative method to assess therapy efficacy. We conducted a systematic review with subsequent meta-analysis of primary studies to assess the prognostic value of sequential liquid biopsies in patients with metastatic colorectal cancer treated with systemic therapy.</div></div><div><h3>Methods</h3><div>Randomized, non-randomized, and prospective observational studies, reporting on the change in ctDNA concentration in total cell-free DNA over the course of systemic therapy of patients treated for metastatic colorectal cancer to predict treatment response according to RECIST criteria were included.</div></div><div><h3>Results</h3><div>Fifty-six studies involving 3735 evaluable patients with metastatic colorectal cancer were included in the meta-analysis. ctDNA increase during systemic therapy as compared to baseline was strongly associated with progression-free survival (HR: 2.44, 95% CI: 2.02–2.95) and overall survival (HR: 2.53, 95% CI: 2.01–3.18), which were reported in 39 and 33 studies, respectively.</div></div><div><h3>Conclusion</h3><div>Our analyses underscore the strong prognostic value of longitudinal plasma-based ctDNA analysis through liquid biopsy in mCRC patients. Subsequent research should evaluate the role of ctDNA in guiding therapy decisions, particularly in identifying patients likely to benefit from continuation or change of systemic therapy. While further standardization of ctDNA testing remains necessary, current evidence supports integrating serial ctDNA monitoring into upcoming clinical mCRC intervention trials, to lay the groundwork for its inclusion into future RECIST versions.</div></div><div><h3>Protocol registration</h3><div>The protocol for this review was registered on PROSPERO (CRD42023420012).</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102999"},"PeriodicalIF":10.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724589","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}
{"title":"Management changes and survival outcomes for cancer patients after multidisciplinary team discussion; a systematic review and meta-analysis","authors":"Gabrielle J. Williams , John F. Thompson","doi":"10.1016/j.ctrv.2025.102997","DOIUrl":"10.1016/j.ctrv.2025.102997","url":null,"abstract":"<div><h3>Objective</h3><div>Multidisciplinary team (MDT) review of cancer patients has become routine in many institutions worldwide. The process seeks to ensure correct diagnosis and staging, optimise treatment decisions and improve outcomes. The aim of this study was to measure any differences in management and survival of cancer patients reviewed at an MDT meeting compared to patients not reviewed or with management plans made prior to MDT review.</div></div><div><h3>Methods and Analysis</h3><div>A PRISMA-compliant systematic review was undertaken with searches of Medline, Embase and the Cochrane Trials Register to 7 June 2024, with no restrictions on language or era.</div></div><div><h3>Results</h3><div>From 2832 titles, 179 comparative studies were identified. Hazard ratios (HRs) for death, generated from multivariable analyses, were reported in 37 studies that included 56,187 patients but estimates were highly variable (I<sup>2</sup> 87 %), ranging from HR 0.1 to 0.96. While the magnitude of the benefit for patients after MDT review was variable, all 37 studies reported a reduced risk of death for MDT-reviewed patients compared to non-reviewed patients. Sub-group analyses based on the patient’s cancer type reduced heterogeneity in patients with breast and hepatocellular carcinomas and suggested a reduced risk of death in MDT-reviewed patients compared to those not reviewed (HR 0.86, 95 %CI 0.79–0.93, I<sup>2</sup> 56 %, p = 0.0001 and HR 0.82, 95 %CI 0.76–0.88, I<sup>2</sup> 36 %, p < 0.00001, respectively).</div></div><div><h3>Conclusion</h3><div>Extensive evidence shows a survival benefit for cancer patients discussed at an MDT meeting but there is considerable variation in the reported magnitude of that benefit, ranging from a 4% to a 90% reduction in the risk of death.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102997"},"PeriodicalIF":9.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703597","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}
F. Javier Muñoz-Carrillo , Marta Garcia de Herreros , David Carrillo , Olenka Peralta , Caterina Aversa , Laia Fernández-Mañas , Laura Ferrer-Mileo , Mariana Altamirano , Òscar Reig Torras , Natalia Jimenez , Begoña Mellado
{"title":"Exercise in patients with metastatic prostate cancer: A comprehensive review","authors":"F. Javier Muñoz-Carrillo , Marta Garcia de Herreros , David Carrillo , Olenka Peralta , Caterina Aversa , Laia Fernández-Mañas , Laura Ferrer-Mileo , Mariana Altamirano , Òscar Reig Torras , Natalia Jimenez , Begoña Mellado","doi":"10.1016/j.ctrv.2025.102996","DOIUrl":"10.1016/j.ctrv.2025.102996","url":null,"abstract":"<div><div>Prostate cancer (PC) is one of the most prevalent malignancies worldwide. Metastatic PC remains an incurable disease, with the androgen receptor (AR) pathway being the primary driver of tumor progression and the main target for therapeutic strategies. Thus, patients usually undergo long-term treatments, particularly androgen deprivation therapy (ADT), which can worsen the intrinsic deterioration in quality of life (QoL) caused by the disease burden. Increasing evidence supports the use of physical activity (PA) and structured exercise (EX) as complementary measures to mitigate treatment-related adverse effects and improve clinical outcomes across tumor types. EX has shown benefits across multiple systems and plays a significant role in modulating tumor progression through several cellular pathways. Furthermore, it has confirmed potential to alleviate cancer-related symptoms while enhancing functional capacity and tolerability of treatment. This review gathers the current evidence regarding the impact of PA and EX on patients with metastatic PC, integrating both epidemiological and interventional studies. Despite promising findings, most of the available evidence is documented on non-metastatic populations, highlighting the need for directed studies in advanced disease settings. Future research is needed in metastatic PC patients, in order to assess long-term impacts of EX in this population.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102996"},"PeriodicalIF":9.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694744","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}
Martina Bortolot , Jordi Remon , Paolo Bironzo , Francesco Cortiula , Jessica Menis , Sze Wai Chan , Robin van Geel , Noemi Reguart , Oscar Arrieta , Giannis Mountzios , Anne-Marie C. Dingemans , Benjamin Besse , Lizza E.L. Hendriks
{"title":"De-escalation strategies with targeted therapies in non-small cell lung cancer","authors":"Martina Bortolot , Jordi Remon , Paolo Bironzo , Francesco Cortiula , Jessica Menis , Sze Wai Chan , Robin van Geel , Noemi Reguart , Oscar Arrieta , Giannis Mountzios , Anne-Marie C. Dingemans , Benjamin Besse , Lizza E.L. Hendriks","doi":"10.1016/j.ctrv.2025.102995","DOIUrl":"10.1016/j.ctrv.2025.102995","url":null,"abstract":"<div><div>Targeted therapies (TT) for non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA), particularly <em>EGFR</em>-mutant and <em>ALK</em>-rearranged tumors, have become the standard of care across nearly all stages of the disease. However, the arbitrarily defined dose and treatment duration of TT, as well as the financial cost of these drugs, reduce their availability worldwide. Pharmacokinetic and pharmacodynamic properties of TT suggest that doses of some TT are overestimated as there is limited evidence supporting a direct relationship between therapeutic intensity and outcomes. This can lead to overtreatment of patients, resulting in an increased risk of toxicity without enhanced efficacy. Some academic initiatives have been launched aiming to explore de-escalating strategies with TT, either reducing the dose or the duration of these drugs. These approaches can decrease the risk of adverse events positively impacting patients’ quality of life, without compromising efficacy, while reducing economic impact. In this review, we summarize current data regarding de-escalating strategies with TT, ongoing trials and challenges of this approach.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102995"},"PeriodicalIF":9.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663353","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}
{"title":"Palliative systemic therapy for locally advanced or metastatic salivary duct carcinoma: A comprehensive review","authors":"Masafumi Kanno , Satoshi Kano , Yoshinori Imamura , Daisuke Kawakita , Norihiko Narita , Yuichiro Tada , Yumi Ito , Taiyo Morikawa , Yoshimasa Imoto , Yukinori Kato , Tetsuji Takabayashi , Shigeharu Fujieda","doi":"10.1016/j.ctrv.2025.102993","DOIUrl":"10.1016/j.ctrv.2025.102993","url":null,"abstract":"<div><div>Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy of the salivary glands. For patients ineligible for curative surgery or definitive radiotherapy, treatment options remain limited owing to the absence of standardized therapeutic protocols. This review draws upon major salivary gland cancer guidelines and integrates molecular profiles with clinical response data to propose an evidence-based treatment algorithm that stratifies patients into four groups according to the expression status of human epidermal growth factor receptor 2 (HER2) and androgen receptor (AR).</div><div>In HER2-positive tumors, HER2-targeted therapy constitutes the standard of care, with trastuzumab plus docetaxel providing clinical benefit. Antibody-drug conjugates, such as trastuzumab deruxtecan, have demonstrated efficacy even in patients with disease progression during trastuzumab-based therapy. In AR-positive tumors, androgen deprivation therapy, particularly combined androgen blockade, has demonstrated clinical activity, though concurrent molecular characteristics may influence treatment outcomes.</div><div>In HER2-positive/AR-positive tumors, HER2-targeted therapy is generally prioritized, although the absence of validated predictive biomarkers and defined thresholds remains a clinical challenge. For HER2-negative and AR-negative tumors, or those refractory to either or both targeted approaches, cytotoxic chemotherapy remains a viable option. Immune checkpoint inhibitors may offer benefits in tumors with high PD-L1 expression, although data on their role in SDC remain limited. Next-generation sequencing is recommended to identify actionable alterations (e.g., <em>NTRK</em>, <em>BRAF</em>, <em>FGFR</em>, <em>HRAS</em>) that may guide targeted therapy or clinical trial enrollment. Integrating comprehensive molecular profiling into treatment decision-making is essential to optimizing outcomes in advanced SDC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102993"},"PeriodicalIF":9.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655636","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}
{"title":"Long-term surveillance recommendations for young adult cancer survivors","authors":"Katharina Egger-Heidrich , Franziska Wolters , Mareike Frick , Teresa Halbsguth , Theresa Müller , Hannah Woopen , Kristin Tausche , Diana Richter , Judith Gebauer","doi":"10.1016/j.ctrv.2025.102992","DOIUrl":"10.1016/j.ctrv.2025.102992","url":null,"abstract":"<div><h3>Background</h3><div>Advancements in cancer treatment have led to increased survival rates among young adult cancer survivors (YACS). However, these individuals face unique long-term health risks, including secondary malignancies, cardiovascular disease, and psychosocial challenges. Effective long-term surveillance strategies are critical to mitigating these risks and improving health outcomes. This scoping review aims to summarize existing recommendations for long-term surveillance of YACS, identify gaps in current guidelines, and highlight areas for future research.</div></div><div><h3>Methods</h3><div>A scoping review was conducted using Pubmed focusing on peer-reviewed literature published between January 2015 and January 2025 that addresses post-treatment (>5 years after diagnosis) follow-up strategies for YACS. The review synthesizes recommendations across various cancer types, treatment modalities, and long-term effects.</div></div><div><h3>Results</h3><div>The review identified 32 recommendations. Of all eligible articles initially retrieved, 169 different articles were included after screening and eligibility. Findings indicate a lack of standardized, age-specific surveillance guidelines, with most recommendations adapted from pediatric or adult oncology frameworks. Emerging evidence suggests that risk-based, personalized surveillance approaches—incorporating genetic predisposition, treatment history, and lifestyle factors—may optimize long-term health outcomes.</div></div><div><h3>Discussion</h3><div>This review underscores the need for age-appropriate, evidence-based surveillance guidelines tailored to YACS and highlights the importance of multidisciplinary care models to support survivorship. Future research should focus on developing standardized, risk-stratified surveillance protocols and evaluating their impact on health outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102992"},"PeriodicalIF":9.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606174","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}
Zoulikha M. Zaïr , Gemma Butterworth , Mariam Shalaby , Eduard Oštarijaš , Fiona Thisthlethwaite
{"title":"T-cell engager toxicity in clinical phase trials; A systematic review and meta-analysis","authors":"Zoulikha M. Zaïr , Gemma Butterworth , Mariam Shalaby , Eduard Oštarijaš , Fiona Thisthlethwaite","doi":"10.1016/j.ctrv.2025.102991","DOIUrl":"10.1016/j.ctrv.2025.102991","url":null,"abstract":"<div><div>Engineered to activate a patient’s own immune response, T Cell Engagers (TCEs) are positioned to mediate T cell directed cytotoxicity through targeted engagement of a tumour antigen. Despite their attractive properties TCE therapies have yet to be widely used in the treatment of solid tumours with several obstacles that include adverse toxicity profiles.</div><div>This systematic review and <em>meta</em>-analysis assessed the toxicity associated with T-cell engagers (TCEs) in the treatment of solid tumours. Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus. Prevalence data from the identified primary studies was pooled using an inverse variance method with a restricted maximum likelihood estimator. Freeman-Tukey double arcsine transformation to determine toxicity prevalence and confidence intervals.</div><div>A total of 1147 publications were identified of which 30 were included for systematic review. Toxicity profiles from 17 TCEs, comprising 9 different ligands that utilised the CD3, CD40, CD28 or CD64 signalling pathways were characterised in this study. Of these studies, 21 publications were included for <em>meta</em>-analysis, focussing on four TCEs: catumaxomab, ertumaxomab, tebentafusb, and MDX-H210. Meta-analysis found that the most prevalent toxicities were gastrointestinal and inflammatory. Subgroup analysis revealed that Gastrointestinal toxicity (GI) toxicity was independent of tumour type or ligand. Cytokine Release Syndrome (CRS) is potentially being under-reported due to challenges of differentiation of CRS from other inflammatory mediated constituent symptoms, although Fc-independent TCEs were linked to lower inflammatory toxicity. The review highlights TCE-dependent toxicity profiles and highlights key features that may ameliorate TCE tolerance.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102991"},"PeriodicalIF":9.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588857","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}
Paul K. Paik , Wade T. Iams , Hatim Husain , Richard M. O’Hara Jr , Emmanuel Adewusi , Xiuning Le
{"title":"Tepotinib in patients with MET exon 14 skipping non-small cell lung cancer","authors":"Paul K. Paik , Wade T. Iams , Hatim Husain , Richard M. O’Hara Jr , Emmanuel Adewusi , Xiuning Le","doi":"10.1016/j.ctrv.2025.102990","DOIUrl":"10.1016/j.ctrv.2025.102990","url":null,"abstract":"<div><div>The management of non-small cell lung cancer (NSCLC) has been transformed by the identification of specific therapies which target oncogenic drivers, including <em>MET</em> exon 14 (<em>MET</em>ex14) skipping, which occurs in 3–4% of patients. The development of selective MET inhibitors, such as tepotinib, has provided much-needed oral, targeted treatment options for these patients who otherwise have poor outcomes. In the largest trial involving patients with <em>MET</em>ex14 skipping NSCLC, the Phase II VISION study, tepotinib demonstrated robust and durable efficacy, which was especially notable when used in the first-line setting. Subgroup analyses demonstrated consistent efficacy in older and younger patients, Asian patients, and patients with brain metastases. The trial supported initial approval of tepotinib in Japan in 2020 and later in the US (accelerated approval: 2021; full approval: 2024) and many other countries worldwide. Here we delve into published literature on tepotinib, overview the mechanism of action and pharmacology, and provide a deep-dive into data from the pivotal VISION study, examining long-term outcomes, insights relevant for treatment sequencing, and biomarker analyses. We also discuss real-world data for tepotinib, indirect comparisons versus immuno- and/or chemotherapy, and provide experience from clinical practice, including guidance on managing adverse events, to provide a valuable aid for clinical practitioners.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102990"},"PeriodicalIF":10.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722878","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}
{"title":"A systematic review of phase I trials in patients with ovarian cancer","authors":"Giuliana Pavone , Federica Martorana , Vincenza Ricco , Esteban Andres Ciliberti , Marta Nerone , Cristiana Sessa , Ilaria Colombo","doi":"10.1016/j.ctrv.2025.102982","DOIUrl":"10.1016/j.ctrv.2025.102982","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC) is the leading cause of death among gynecological malignancies, with limited treatment options for advanced and platinum-resistant disease. This systematic review analyzes phase I trials to assess recent therapeutic advancements.</div></div><div><h3>Methods</h3><div>We performed a systematic review of phase I trials in OC, published between 2012 and 2023, retrieving data on trial characteristics and outcomes. Studies were classified according to the tested treatment strategies into chemotherapy-only (CO), chemotherapy + non-chemotherapy agents (CNC) and chemotherapy-free (CF).</div></div><div><h3>Results</h3><div>78 trials were included, with more than 50 % of them published in the last four years. Overall, chemotherapy and immunotherapy were the most investigated agents. Fourteen trials (17.9 %) evaluated a CO strategy, 42 (53.8 %) a CNC combination and 22 (28.2 %) a CF therapy. Dose-limiting toxicities and toxic deaths were observed in 71 % and 100 % of CO studies, in 45.2 % and 21 % of CNC trials and in 37.4 % and 13.6 % of CF trials, respectively. CNC regimens outperformed the other treatment types in terms of efficacy outcomes, including overall response rate (11.5 % CO; 32.2 % CNC; 25.5 % CF), clinical benefit rate (40 % CO; 62 % CNC; 52 % CF) and median progression free survival (mPFS 5.9 months CO; 6.45 months CNC; 4.85 months CF). Trials enrolling platinum resistant or agnostic patients displayed worse clinical outcomes.</div></div><div><h3>Conclusions</h3><div>In the last years, there has been an increasing number of phase 1 trials assessing new agents and new combinations in patients with OC. Chemotherapy-free strategies display a more favorable safety profile, while regimens combining CNC agents seem to be more effective compared to CO approaches.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102982"},"PeriodicalIF":9.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502652","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}