Cancer treatment reviews最新文献

{"title":"The more the merrier? Evidence and efficacy of immune checkpoint- and tyrosine kinase inhibitor combinations in advanced solid cancers","authors":"Angelika M. Starzer ,&nbsp;Ladislaia Wolff ,&nbsp;Petar Popov ,&nbsp;Barbara Kiesewetter ,&nbsp;Matthias Preusser ,&nbsp;Anna S. Berghoff","doi":"10.1016/j.ctrv.2024.102718","DOIUrl":"10.1016/j.ctrv.2024.102718","url":null,"abstract":"<div><p>Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have gained therapeutical significance in cancer therapy over the last years. Due to the high efficacy of each substance group, additive or complementary effects are considered, and combinations are the subject of multiple prospective trials in different tumor entities. The majority of available data results from clinical phase I and II trials. Although regarded as well-tolerated therapies ICI-TKI combinations have higher toxicities compared to monotherapies of one of the substance classes and some combinations were shown to be excessively toxic leading to discontinuation of trials. So far, ICI-TKI combinations with nivolumab + cabozantinib, pembrolizumab + axitinib, avelumab + axitinib, pembrolizumab + lenvatinib have been approved in advanced renal cell (RCC), with pembrolizumab + lenvatinib in endometrial carcinoma and with camrelizumab + rivoceranib in hepatocellular carcinoma (HCC). Several ICI-TKI combinations are currently investigated in phase I to III trials in various other cancer entities. Further, the optimal sequence of ICI-TKI combinations is an important subject of investigation, as cross-resistances between the substance classes were observed. This review reports on clinical trials with ICI-TKI combinations in different cancer entities, their efficacy and toxicity.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102718"},"PeriodicalIF":11.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224000458/pdfft?md5=dc176d81613cd91a6914c1da75714dfd&pid=1-s2.0-S0305737224000458-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140182271","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}

{"title":"Bridging gaps in cancer cachexia Care: Current insights and future perspectives","authors":"Carlotta Bianchini ,&nbsp;Pierluigi Bonomo ,&nbsp;Paolo Bossi ,&nbsp;Riccardo Caccialanza ,&nbsp;Alessandra Fabi","doi":"10.1016/j.ctrv.2024.102717","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102717","url":null,"abstract":"<div><p>Cachexia is characterized by severe weight loss and skeletal muscle depletion, and is a threat to cancer patients by worsening their prognosis. International guidelines set indications for the screening and diagnosis of cancer cachexia and suggest interventions (nutritional support, physical exercise, and pharmacological treatments). Nevertheless, real-life experience not always aligns with such indications. We aimed to review the current state of the field and the main advancements, with a focus on real-life clinical practice from the perspectives of oncologists, nutrition professionals, and radiologists. Pragmatic solutions are proposed to improve the current management of the disease, emphasizing the importance of increasing awareness of clinical nutrition’s benefits, fostering multidisciplinary collaboration, promoting early identification of at-risk patients, and leveraging available resources. Given the distinct needs of patients who are receiving oncologic anti-cancer treatments and those in the follow-up phase, the use of tailored approaches is encouraged. The pivotal role of healthcare professionals in managing patients in active treatment is highlighted, while patient and caregiver empowerment should be strengthened in the follow-up phase. Telemedicine and web-based applications represent valuable tools for continuous monitoring of patients, facilitating timely and personalized intervention through effective communication between patients and healthcare providers. These actions can potentially improve the outcomes, well-being, and survival of cancer patients with cachexia.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102717"},"PeriodicalIF":11.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224000446/pdfft?md5=fedc344b1171acad1c3fd0aac4e9a70a&pid=1-s2.0-S0305737224000446-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179730","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}

{"title":"Pancreatic cancer biomarkers: A pathway to advance in personalized treatment selection","authors":"Elena Brozos-Vázquez ,&nbsp;Marta Toledano-Fonseca ,&nbsp;Nicolás Costa-Fraga ,&nbsp;María Victoria García-Ortiz ,&nbsp;Ángel Díaz-Lagares ,&nbsp;Antonio Rodríguez-Ariza ,&nbsp;Enrique Aranda ,&nbsp;Rafael López-López","doi":"10.1016/j.ctrv.2024.102719","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102719","url":null,"abstract":"<div><p>Pancreatic cancer is one of the tumors with the worst prognosis, and unlike other cancers, few advances have been made in recent years. The only curative option is surgery, but only 15–20% of patients are candidates, with a high risk of relapse. In advanced pancreatic cancer there are few first-line treatment options and no validated biomarkers for better treatment selection. The development of targeted therapies in pancreatic cancer is increasingly feasible due to tumor-agnostic treatments, such as PARP inhibitors in patients with <em>BRCA1</em>, <em>BRCA2</em> or <em>PALB2</em> alterations or immunotherapies in patients with high microsatellite instability/tumor mutational burden. In addition, other therapeutic molecules have been developed for patients with <em>KRAS</em> G12C mutation or fusions in <em>NTRK</em> or <em>NRG1</em>. Consequently, there has been a growing interest in biomarkers that may help guide targeted therapy in pancreatic cancer. Therefore, this review aims to offer an updated perspective on biomarkers with therapeutic potential in pancreatic cancer.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102719"},"PeriodicalIF":11.8,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S030573722400046X/pdfft?md5=96ec3537f15005b18419db44251fc740&pid=1-s2.0-S030573722400046X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140122558","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}

{"title":"Well-differentiated liposarcomas and dedifferentiated liposarcomas: Systemic treatment options for two sibling neoplasms","authors":"A. Kyriazoglou ,&nbsp;A. Pagkali ,&nbsp;I. Kotsantis ,&nbsp;P. Economopoulou ,&nbsp;M. Kyrkasiadou ,&nbsp;M. Moutafi ,&nbsp;N. Gavrielatou ,&nbsp;M. Anastasiou ,&nbsp;A. Boulouta ,&nbsp;A. Pantazopoulos ,&nbsp;M. Giannakakou ,&nbsp;A. Digklia ,&nbsp;A. Psyrri","doi":"10.1016/j.ctrv.2024.102716","DOIUrl":"10.1016/j.ctrv.2024.102716","url":null,"abstract":"<div><p>Well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) account for 60 % of all liposarcomas, reflecting the heterogeneity of this type of sarcoma. Genetically, both types of liposarcomas are characterized by the amplification of <em>MDM2</em> and <em>CDK4</em> genes, which indicates an important molecular event with diagnostic and therapeutic relevance. In both localized WDLPS and DDLPS of the retroperitoneum and the extremities, between 25 % and 30 % of patients have local or distant recurrence, even when perioperatively treated, with clear margins present. The systemic treatment of WDLPS and DDLPS remains a challenge, with anthracyclines as the gold standard for first-line treatment. Several regimens have been tested with modest results regarding their efficacy. Herein we discuss the systemic treatment options for WDLPS and DDLPS and review their reported clinical efficacy results.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102716"},"PeriodicalIF":11.8,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140124695","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":"Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan","authors":"Rebecca S. Heist ,&nbsp;Jacob Sands ,&nbsp;Aditya Bardia ,&nbsp;Toshio Shimizu ,&nbsp;Aaron Lisberg ,&nbsp;Ian Krop ,&nbsp;Noboru Yamamoto ,&nbsp;Takahiro Kogawa ,&nbsp;Saba Al-Hashimi ,&nbsp;Simon S.M. Fung ,&nbsp;Anat Galor ,&nbsp;Francesca Pisetzky ,&nbsp;Priyanka Basak ,&nbsp;Cindy Lau ,&nbsp;Funda Meric-Bernstam","doi":"10.1016/j.ctrv.2024.102720","DOIUrl":"10.1016/j.ctrv.2024.102720","url":null,"abstract":"<div><p>Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor<!--> <!-->2-negative breast cancer (HR+/HER2– BC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC).</p><p>Improved understanding of the adverse events (AEs) that are associated with Dato-DXd and their optimal management is essential to ensure safe and successful administration. Interstitial lung disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, and ocular surface events have been identified as AEs of special interest (AESIs) for which appropriate prevention, monitoring, and management is essential. This article summarizes the incidence of AESIs among patients with HR+/HER2− BC, TNBC, and NSCLC reported in TROPION-PanTumor01. We report our recommendations for AESI prophylaxis, early detection, and management, using experience gained from treating AESIs that occur with Dato-DXd in clinical trials.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102720"},"PeriodicalIF":11.8,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224000471/pdfft?md5=42e58372bfd4d21d42fccffff25e1a90&pid=1-s2.0-S0305737224000471-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140124591","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}

{"title":"How to manage waldenström’s macroglobulinemia in 2024","authors":"Alexander Grunenberg ,&nbsp;Christian Buske","doi":"10.1016/j.ctrv.2024.102715","DOIUrl":"10.1016/j.ctrv.2024.102715","url":null,"abstract":"<div><p>Clinical management of Waldenström’s Macroglobulinemia has seen major progress in the recent years, triggered by our improved understanding of the biology of the disease and the development of new therapies. Based on this there are multiple treatment options available for patients with WM ranging from classical immunochemotherapy to targeted approaches blocking key enzymes involved in lymphoma growth. This review summarizes our current knowledge about diagnostics and treatment of this rare but recurrent lymphoma subtype, which often presents a major clinical challenge in daily clinical life.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102715"},"PeriodicalIF":11.8,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140055896","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":"Tumor-agnostic baskets to N-of-1 platform trials and real-world data: Transforming precision oncology clinical trial design","authors":"Elena Fountzilas ,&nbsp;Apostolia-Maria Tsimberidou ,&nbsp;Henry Hiep Vo ,&nbsp;Razelle Kurzrock","doi":"10.1016/j.ctrv.2024.102703","DOIUrl":"10.1016/j.ctrv.2024.102703","url":null,"abstract":"<div><p>Choosing the right drug(s) for the right patient via advanced genomic sequencing and multi-omic interrogation is the <em>sine qua non</em> of precision cancer medicine. Traditional cancer clinical trial designs follow well-defined protocols to evaluate the efficacy of new therapies in patient groups, usually identified by their histology/tissue of origin of their malignancy. In contrast, precision medicine seeks to optimize benefit in individual patients, i.e., to define who benefits rather than determine whether the overall group benefits. Since cancer is a disease driven by molecular alterations, innovative trial designs, including biomarker-defined tumor-agnostic basket trials, are driving ground-breaking regulatory approvals and deployment of gene- and immune-targeted drugs. Molecular interrogation further reveals the disruptive reality that advanced cancers are extraordinarily complex and individually distinct. Therefore, optimized treatment often requires drug combinations and N-of-1 customization, addressed by a new generation of N-of-1 trials. Real-world data and structured master registry trials are also providing massive datasets that are further fueling a transformation in oncology. Finally, machine learning is facilitating rapid discovery, and it is plausible that high-throughput computing, <em>in silico</em> modeling, and 3-dimensional printing may be exploitable in the near future to discover and design customized drugs in real time.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102703"},"PeriodicalIF":11.8,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140055973","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":"Pharmacological prevention and treatment of opioid-induced constipation in cancer patients: A systematic review and meta-analysis","authors":"K.R.J. Kistemaker ,&nbsp;F. Sijani ,&nbsp;D.J. Brinkman ,&nbsp;A. de Graeff ,&nbsp;G.L. Burchell ,&nbsp;M.A.H. Steegers ,&nbsp;L. van Zuylen","doi":"10.1016/j.ctrv.2024.102704","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102704","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC.&lt;/p&gt;&lt;p&gt;This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review.&lt;/p&gt;&lt;p&gt;Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible.&lt;/p&gt;&lt;p&gt;Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis.&lt;/p&gt;&lt;p&gt;Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD −13.68; 95 % CI −18.38 to −8.98; I&lt;sup&gt;2&lt;/sup&gt; = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31–0.83; I&lt;sup&gt;2&lt;/sup&gt; = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64–2.61, I&lt;sup&gt;2&lt;/sup&gt; = 0 %; MNTX: RR 3.83, 95 % CI 2.81–5.22, I&lt;sup&gt;2&lt;/sup&gt; = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Magnesium oxide and nalde","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102704"},"PeriodicalIF":11.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224000227/pdfft?md5=71786d5672fa6b4f1ee184e40fb33ac1&pid=1-s2.0-S0305737224000227-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041820","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}

{"title":"Cancer genetic counselling for hereditary breast cancer in the era of precision oncology","authors":"M. Pensabene ,&nbsp;A. Calabrese ,&nbsp;C. von Arx,&nbsp;R. Caputo,&nbsp;M. De Laurentiis","doi":"10.1016/j.ctrv.2024.102702","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102702","url":null,"abstract":"<div><p>A relevant percentage of breast cancers (BCs) are tied to pathogenetic (P)/likely pathogenetic (LP) variants in predisposing genes. The knowledge of P/LP variants is an essential element in the management of BC patients since the first diagnosis because it influences surgery and subsequent oncological treatments and follow-up. Moreover, patients with metastatic BCs can benefit from personalized treatment if carriers of P/LP in BRCA1/2 genes. Multigene panels allow the identification of other predisposing genes with an impact on management. Cascade genetic testing for healthy family members allows personalized preventive strategies. Here, we review the advances and the challenges of Cancer Genetic Counseling (CGC). We focus on the area of oncology directed to hereditary BC management describing the peculiar way to lead CGC and how CGC changes over time. The authors describe the impact of genetic testing by targeted approach or universal approach on the management of BC according to the stage at diagnosis. Moreover, they describe the burden of CGC and testing and future perspectives to widely offer testing. A new perspective is needed for models of service delivery of CGC and testing, beyond formal genetic counselling. A broader genetic test can be quickly usable in clinical practice for comprehensive BC management and personalized prevention in the era of precision oncology.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102702"},"PeriodicalIF":11.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224000203/pdfft?md5=df11a66a33e2c56e6989728f2a516d15&pid=1-s2.0-S0305737224000203-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041819","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}

{"title":"Incorporation of anti-PD1 or anti PD-L1 agents to platinum-based chemotherapy for the primary treatment of advanced or recurrent endometrial cancer. A meta-analysis","authors":"Michele Bartoletti ,&nbsp;Marcella Montico ,&nbsp;Domenica Lorusso ,&nbsp;Roberta Mazzeo ,&nbsp;Ana Oaknin ,&nbsp;Lucia Musacchio ,&nbsp;Giovanni Scambia ,&nbsp;Fabio Puglisi ,&nbsp;Sandro Pignata","doi":"10.1016/j.ctrv.2024.102701","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102701","url":null,"abstract":"<div><h3>Importance</h3><p>Various randomized trials have explored the efficacy of combining immune checkpoint inhibitors (ICIs) with first-line chemotherapy in advanced endometrial cancer. We aimed to summarize available data and clarify the benefit of adding immunotherapy according to the DNA mismatch repair status (deficient, dMMR or proficient, pMMR) and the specific type of agent used (anti-PD1 or anti-PD-L1).</p></div><div><h3>Objective</h3><p>To assess whether the addition of ICIs to standard platinum-based chemotherapy enhances progression-free survival (PFS) for patients with advanced endometrial cancer both overall and based on DNA mismatch repair status.</p></div><div><h3>Data sources</h3><p>Electronic databases (PubMed, Embase and Cochrane Library) and conference proceedings were searched for first line, randomized and controlled trials integrating ICIs with chemotherapy for the treatment of advanced endometrial cancer published or presented by November 1, 2023.</p></div><div><h3>Study selection</h3><p>Five studies, comprising 2456 patients (1308 received ICIs with chemotherapy and 1148 treated with chemotherapy alone) met the selection criteria and were included in the analysis. Experimental arms included pembrolizumab, dostarlimab (anti-PD1) and durvalumab, atezolizumab and avelumab (anti-PD-L1) combined with standard three-weekly carboplatin-paclitaxel chemotherapy backbone. Endometrial carcinosarcoma were included in 3 out of 5 trials.</p></div><div><h3>Data extraction and synthesis</h3><p>For comparison of PFS outcomes, extrapolation of hazard ratios (HRs), 95% confidence intervals (CI) and PFS events was performed for each included study in the overall population and according to subgroups. Data analysis was conducted using a random-effects model.</p></div><div><h3>Results</h3><p>The addition of ICIs to chemotherapy improved PFS compared to chemotherapy alone in the overall population (pooled HR, 0.63; 95 % CI, 0.52––0.76; P &lt;.001). In the dMMR subgroup the benefit was more pronounced (pooled HR, 0.34; 95 % CI, 0.27––0.44; P &lt;.001) and not affected by drugs used with pooled HRs of 0.39 (95 % CI, 0.28––0.55; P &lt;.001) and 0.34 (95 % CI, 0.27––0.44; P &lt;.001) for PD-L1 and PD1 inhibitors, respectively. For pMMR patients, a statistically significant benefit in terms of PFS was confirmed only when anti-PD1 were used (anti-PD-1: HR 0.64, 95 % CI: 0.46–0.90, P =.010 vs anti-PD-L1: HR 0.87, 95 % CI: 0.73–1.03, P =.104)</p></div><div><h3>Conclusions and relevance</h3><p>This <em>meta</em>-analysis confirmed the advantage in terms of PFS of adding ICIs to standard platinum-based chemotherapy. While dMMR patients benefit from the incorporation of both anti PD-1 or anti PD-L1, this benefit is confined to the association of anti-PD1 agents in pMMR patients. Updated analysis of trials is awaited to clarify the impact of immunotherapy on overall survival.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"125 ","pages":"Article 102701"},"PeriodicalIF":11.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224000197/pdfft?md5=70aba726898887fdf324df961a3425eb&pid=1-s2.0-S0305737224000197-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139993345","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}