Gynecologic oncology最新文献

{"title":"Oncologic and fertility outcomes in patients with juvenile granulosa cell tumor - a retrospective single centre analysis.","authors":"Giuseppe Marino, Liliana Marchetta, Serena Negri, Filippo Testa, Daniele Lugotti, Giulia Cavallo, Tommaso Grassi, Marta Jaconi, Elena De Ponti, Maria Cristina Bonazzi, Fabio Landoni, Robert Fruscio","doi":"10.1016/j.ygyno.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.ygyno.2024.11.007","url":null,"abstract":"<p><strong>Background: </strong>Granulosa cell tumors (GCTs) are rare neoplasia that account for less than 5 % of all the ovarian tumors. Juvenile GCT histotype is generally observed in adolescent and young women, representing a very rare disease, so only a paucity of data are present in literature. The aim of this study is to analyse the oncologic and fertility outcome in our case series of juvenile GCTs.</p><p><strong>Methods: </strong>Clinicopathological data were retrospectively collected and analysed from a cohort of 30 patients ovarian juvenile GCTs treated at IRCCS San Gerardo dei Tintori Hospital, Monza, between 1980 and 2024.</p><p><strong>Results: </strong>The median age of disease onset was 21.5. Among patients enrolled in the study, 80.0 % (24/30) were stage I (16/26, 1/26 and 7/26 of stage IA, IB and IC, respectively), 6.7 % (2/30) were stage II and 13.3 % stage III (4/30). In 86.7 % (26/30) of patients, a fertility-sparing surgery was carried out, while 13.3.% (4/30) of patients underwent radical surgery. Adjuvant chemotherapy was administered in 20.0 % (6/30) of cases, while 80.0 % (24/30) were followed only with surveillance. Three patients in thirty (10.0 %) relapsed and died of disease despite multi-therapeutic approaches. All of them had advanced stages of disease at time of diagnosis.</p><p><strong>Conclusions: </strong>Juvenile GCT appears to have a good prognosis at stage I disease. However, advanced stage represents a hard challenge for clinicians, showing a high rate of relapse and mortality.</p>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"89-93"},"PeriodicalIF":4.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and therapeutic implication of molecular classification including L1CAM expression in high-risk endometrial cancer","authors":"Andreas Kleppe ,&nbsp;Kristina Lindemann ,&nbsp;Wanja Kildal ,&nbsp;Kari Anne R. Tobin ,&nbsp;Manohar Pradhan ,&nbsp;Ljiljana Vlatkovic ,&nbsp;Maria X. Isaksen ,&nbsp;Håvard E. Danielsen ,&nbsp;Hanne A. Askautrud ,&nbsp;Gunnar B. Kristensen","doi":"10.1016/j.ygyno.2024.11.005","DOIUrl":"10.1016/j.ygyno.2024.11.005","url":null,"abstract":"<div><h3>Introduction</h3><div>The role of molecular classification and L1CAM in high-risk endometrial cancer is uncertain. We aimed to determine the association of molecular profiling and L1CAM with patterns of relapse and survival.</div></div><div><h3>Material and methods</h3><div>This retrospective cohort study included patients referred to Department for Gynecologic Oncology, Oslo University Hospital between January 1, 2006 and December 31, 2017. L1CAM expression and molecular profiling according to ProMisE was performed. Main outcome was time to recurrence (TTR) and cancer specific survival (CSS).</div></div><div><h3>Results</h3><div>Of 489 patients, 486 could be molecular classified. Thirty-seven (8 %) had <em>POLE</em> mutated tumors, 148 (30 %) had MMRd tumors, 189 (39 %) had p53 abnormal tumors, and 112 (23 %) had NSMP tumors. High L1CAM expression was observed in 256 (53 %), low in 227 (46 %) tumors (6 (1 %) missing). ProMisE was significant for TTR but not for CSS in multivariable analysis. L1CAM was significant in multivariable analysis for both TTR and CSS. In a multivariable model with ProMisE and L1CAM expression in the same multivariable model, ProMisE lost significance while L1CAM remained significant. Patients with <em>POLE</em> mutated tumors entailed an excellent prognosis while patients with p53 abnormal or L1CAM overexpressing tumors entailed a poor prognosis with a high frequency of distant recurrences. Patients with MMRd tumors, NSMP and p53 abnormal tumors with low L1CAM had an intermediate prognosis.</div></div><div><h3>Conclusions</h3><div>L1CAM is an additional adverse factor in the p53 abnormal and NSMP groups. These groups need special attention in studies intensifying adjuvant treatment.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"Pages 80-88"},"PeriodicalIF":4.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical trial enrollment during first course of gynecologic cancer treatment and survival","authors":"Wafa Khadraoui ,&nbsp;Jennifer A. Sinnott ,&nbsp;Caitlin E. Meade ,&nbsp;Jesse Plascak ,&nbsp;Autumn Carey ,&nbsp;Floor J. Backes ,&nbsp;Robert L. Dood ,&nbsp;Britton Trabert ,&nbsp;Ashley S. Felix","doi":"10.1016/j.ygyno.2024.11.003","DOIUrl":"10.1016/j.ygyno.2024.11.003","url":null,"abstract":"<div><h3>Objective</h3><div>Among gynecologic cancer patients, it is unclear whether participation in clinical trials impacts survival outcomes. In addition, given the known racial and ethnic disparities in gynecologic cancer trial enrollment, it is important to assess whether clinical trial enrollment is similarly related to overall survival among racial and ethnic minorities. Therefore, we examined associations between clinical trial enrollment and overall survival and potential effect modification by race/ethnicity and cancer site among gynecologic cancer patients.</div></div><div><h3>Methods</h3><div>We used the National Cancer Database to identify women diagnosed with a cervical, ovarian, or uterine cancer from 2004 to 2020 (<em>N</em> = 861,817). Race/ethnicity categories included American Indian/Alaska Native, Asian, Black, Hispanic (any race), Native Hawaiian/Pacific Islander, and White. We used stratified Cox proportional hazards regression to estimate univariable and multivariable-adjusted hazard ratios and 95% confidence intervals for associations of clinical trial enrollment and overall survival. Effect modification by race/ethnicity and cancer site was assessed with multiplicative interaction terms in separate models.</div></div><div><h3>Results</h3><div>Median follow-up was 56.0 months (range 0.03–229.4 months). Clinical trial enrollment was related to improved overall survival among gynecologic cancer patients in the overall study population (hazard ratio = 0.90, 95% confidence interval = 0.82–0.99). Neither race/ethnicity (<em>p</em> = 0.34) nor cancer site (<em>p</em> = 0.09) modified the association.</div></div><div><h3>Conclusion</h3><div>Clinical trial enrollment was associated with improved outcomes for gynecologic cancer patients. These findings are important in demonstrating that participation in clinical trials, regardless of therapeutic treatment assignment, is related to better outcomes.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"Pages 59-64"},"PeriodicalIF":4.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized controlled trial of an online support group addressing psychosexual distress among women treated for gynecologic cancer","authors":"Catherine C. Classen ,&nbsp;Meredith L. Chivers ,&nbsp;Lori A. Brotto ,&nbsp;Lisa Barbera ,&nbsp;Jeanne Carter ,&nbsp;John Koval ,&nbsp;John W. Robinson ,&nbsp;Sarah E. Ferguson","doi":"10.1016/j.ygyno.2024.10.032","DOIUrl":"10.1016/j.ygyno.2024.10.032","url":null,"abstract":"<div><h3>Objective</h3><div>To assess whether a 12-week, professionally facilitated, asynchronous online support group would reduce sexual distress (primary outcome) and improve sexual function, body image, depression symptoms, relationship satisfaction, and social support (secondary outcomes) in women treated for gynecologic cancer.</div></div><div><h3>Methods</h3><div>Participants were 398 women recruited from three Canadian provinces and one American cancer center in cohorts of 40. Participants were randomized (50:50 odds) to either the immediate treatment condition (ITC) or the waitlist control condition (WCC). Eligibility included: completed treatment for gynecologic cancer, disease-free for at least 3 months, no more than 5 years post-diagnosis, met criteria for psychosexual distress, willing to discuss sexual concerns, 18 years or older, English speaking, and access to a computer. Participants in the ITC received a 12-week online group along with psychoeducational material each week to stimulate discussion. Two 90-min synchronous sessions were offered in weeks 4 and 8.</div></div><div><h3>Results</h3><div>Reductions in sexual distress for ITC were not significantly different compared to WCC. Similarly, no treatment effects were observed for body image, depression, relationship satisfaction, or social support. ITC showed statistically significant improvements in sexual functioning compared to WCC, but these gains were not retained at 4-month follow-up.</div></div><div><h3>Conclusion</h3><div>Treatment effects were modest, although in the expected direction. As this study was underpowered, it offers preliminary evidence that an asynchronous, online psychoeducational support group may confer positive benefits for women's sexual functioning. The efficiency, convenience, and accessibility of online interventions has significant potential to close gaps in women's access to evidence-based sexual health care.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"Pages 73-79"},"PeriodicalIF":4.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repair Assisted Damage Detection (RADD) as a predictive biomarker for immunotherapy response in ovarian cancer","authors":"Manoj Sonavane ,&nbsp;Jenna Hedlich-Dwyer ,&nbsp;Valeria L. Dal Zotto ,&nbsp;Min Tang ,&nbsp;John Nemunaitis ,&nbsp;Laura Stanbery ,&nbsp;Adam Walter ,&nbsp;Ernest Bognar ,&nbsp;Rodney P. Rocconi ,&nbsp;Natalie R. Gassman","doi":"10.1016/j.ygyno.2024.11.006","DOIUrl":"10.1016/j.ygyno.2024.11.006","url":null,"abstract":"<div><h3>Objective</h3><div>Genomic instability has been proposed as a predictive biomarker for immunotherapy in ovarian cancer. We tested a method for measuring DNA damage, a direct measure of genomic instability, in ovarian tumors and its ability to predict immunotherapy response to Vigil (gemogenovatucel-T).</div></div><div><h3>Methods</h3><div>Eighty-two formalin-fixed paraffin-embedded tumors from the VITAL trial (<span><span>NCT02346747</span><svg><path></path></svg></span>) underwent DNA damage assessment using Repair Assisted Damage Detection (RADD). VITAL tested maintenance Vigil therapy vs. placebo for stage IIIB-IV newly diagnosed ovarian cancer in clinical complete response. DNA lesion levels determined by RADD were scored and assessed against patient survival outcomes, expression of CD39, and gene expression signatures.</div></div><div><h3>Results</h3><div>A graduated distribution of RADD scores occurred across all 82 ovarian samples. RADD scores were able to predict HR status (<em>p</em> &lt; 0.001). RADD demonstrated a significant Pearson's correlation with suggested Vigil biomarker CD39 (<em>r</em> = 0.473; p &lt; 0.001), specifically within HRP tumors (<em>r</em> = 0.57; <em>p</em> = 0.002). High RADD scores correlated with worse recurrent free survival (RFS) in the placebo arm of the trial (7.9 vs. 14.7 months, high vs. low; <em>p</em> = 0.066). High RADD scores were also predictive of significant RFS over 39.4 months with Vigil compared to placebo (25.1 vs. 11.7 months, <em>p</em> = 0.005) and improved, but not significantly, OS with 38.8 vs. 31.8 months.</div></div><div><h3>Conclusions</h3><div>RADD revealed DNA repair proficiency without mutation signatures or expression profiling. High DNA damage levels show improved survival for Vigil maintenance therapies and are correlated with immune evasion proteins. The persistence of DNA lesions in the genomic DNA offers a new biomarker for immunotherapy patient stratification.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"Pages 65-72"},"PeriodicalIF":4.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insurance coverage and access to gynecologic oncology: Where are we now","authors":"Lakeisha Mulugeta-Gordon ,&nbsp;Anna Jo Bodurtha Smith","doi":"10.1016/j.ygyno.2024.11.001","DOIUrl":"10.1016/j.ygyno.2024.11.001","url":null,"abstract":"<div><div>In the United Sates, over 115,000 individuals are diagnosed with a gynecologic cancer annually with access to a gynecologic oncologist and evidence-based treatment remaining a persistent challenge. Coverage decisions by private and public insurance, including Medicaid and Medicare, play key roles in access to care, impacting oncologic outcomes. The expansion of Medicaid insurance under the Affordable Care Act improved early diagnosis, treatment, and survival in gynecologic cancers, but disparities remain for individuals in non-Medicaid expansion states. For individuals with Medicare or private insurance, coverage gaps and high out-of-pocket costs are barriers to cancer care, particularly for novel therapeutic treatments. Efforts to streamline care access, expand clinical trial participation, and reduce administrative burdens continue. Addressing these disparities require improving insurance literacy in patients and clinicians, coordination, and community partnerships to support equitable and comprehensive gynecologic cancer care.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"Pages 56-58"},"PeriodicalIF":4.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse events in the placebo arm of SOLO2/ENGOT-Ov21 maintenance trial of olaparib in recurrent ovarian cancer","authors":"Katherine Elizabeth Francis ,&nbsp;Sandy Simon ,&nbsp;Val Gebski ,&nbsp;Florence Joly ,&nbsp;Jonathan A. Ledermann ,&nbsp;Richard T. Penson ,&nbsp;Amit M. Oza ,&nbsp;Jacob Korach ,&nbsp;Nuria Lainez ,&nbsp;Sabrina Chiara Cecere ,&nbsp;Giulia Tasca ,&nbsp;Martina Gropp-Meier ,&nbsp;Keiichi Fujiwara ,&nbsp;Elizabeth S. Lowe ,&nbsp;Michael Friedlander ,&nbsp;Eric Pujade-Lauraine ,&nbsp;Chee Khoon Lee","doi":"10.1016/j.ygyno.2024.11.004","DOIUrl":"10.1016/j.ygyno.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>In women with platinum sensitive recurrent ovarian cancer (PSROC) undergoing maintenance treatment, adverse events (AEs) not attributable to the current treatment are not well understood. We used data from SOLO2/ENGOT-Ov21 to evaluate AEs reported in the placebo arm and to explore their longitudinal trajectories.</div></div><div><h3>Methods</h3><div>SOLO2/ENGOT-Ov21 (<span><span>NCT01874353</span><svg><path></path></svg></span>) randomly assigned 295 PSROC participants with a <em>BRCA1/2</em> mutation to maintenance olaparib tablets (<em>N</em> = 196) or matching placebo (<em>N</em> = 99). For those assigned to placebo, we analyzed the AE (CTCAE v4.0) data including type, grade, time of onset and resolution, and attribution by investigator.</div></div><div><h3>Results</h3><div>Amongst 99 participants who received placebo 788 AEs were reported (95 % reporting ≥1 AE). Twenty-two percent of participants reported at least one grade ≥ 3 AE. Grade ≥ 2 AEs that persisted for over 100 days affected 21 % of participants. Recurring grade ≥ 1 AEs were experienced by 44 % of participants. Study investigators attributed 25 % of all AEs to the placebo treatment, with neutropenia (88 %), nausea (52 %) and thrombocytopenia (50 %) most attributed. Three percent of participants had a dose reduction, 19 % had treatment delays, and 2 % had permanent treatment discontinuation, due to AEs attributed to placebo.</div></div><div><h3>Conclusion</h3><div>Virtually all PSROC participants in the SOLO2/ENGOT-Ov21 experienced one or more AE whilst on placebo. Furthermore, study investigators attributed one quarter of AEs to be related to placebo therapy and dose alterations and treatment changes were made based on these AE. Further work is needed to improve measurement and categorization of AEs in trials of maintenance therapy in PSROC.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"Pages 50-55"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of dostarlimab in combination with chemotherapy in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer in a phase 3, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY)","authors":"Matthew A. Powell ,&nbsp;David Cibula ,&nbsp;David M. O'Malley ,&nbsp;Ingrid Boere ,&nbsp;Mark S. Shahin ,&nbsp;Antonella Savarese ,&nbsp;Dana M. Chase ,&nbsp;Lucy Gilbert ,&nbsp;Destin Black ,&nbsp;Jørn Herrstedt ,&nbsp;Sudarshan Sharma ,&nbsp;Stefan Kommoss ,&nbsp;Michael A. Gold ,&nbsp;Anna M. Thijs ,&nbsp;Kari Ring ,&nbsp;Magnus Frödin Bolling ,&nbsp;Joseph Buscema ,&nbsp;Sarah E. Gill ,&nbsp;Paul Nowicki ,&nbsp;Nicole Nevadunsky ,&nbsp;Mansoor Raza Mirza","doi":"10.1016/j.ygyno.2024.10.022","DOIUrl":"10.1016/j.ygyno.2024.10.022","url":null,"abstract":"<div><h3>Objectives</h3><div>Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.</div></div><div><h3>Methods</h3><div>Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with blinded independent central review, sensitivity analyses of the source-verified population compared with the randomized population, and analysis of safety in this population were completed.</div></div><div><h3>Results</h3><div>In total, 118 patients with dMMR/MSI-H were enrolled in the RUBY trial (53, dostarlimab arm; 65, placebo arm). At the first interim analysis, a 72% reduction in the risk of progression or death (<em>P</em> &lt; 0.0001) was seen with dostarlimab plus carboplatin-paclitaxel by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which was consistent with blinded independent central review per RECIST v1.1. Likewise, sensitivity analyses of the source-verified dMMR/MSI-H population compared with the randomized dMMR/MSI-H population were consistent for progression-free survival and overall survival. Safety results seen in the dMMR/MSI-H population were similar to those previously reported for the overall population.</div></div><div><h3>Conclusions</h3><div>All primary and secondary efficacy assessments demonstrate the consistent benefit of dostarlimab plus carboplatin-paclitaxel. The improvements seen in survival and the manageable safety profile support the favorable benefit–risk profile for dostarlimab plus carboplatin-paclitaxel in patients with dMMR/MSI-H primary advanced or recurrent EC.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"Pages 40-49"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of dostarlimab plus carboplatin-paclitaxel for primary advanced or recurrent endometrial cancer from a US payer perspective","authors":"Robert L. Coleman ,&nbsp;Solomon J. Lubinga ,&nbsp;Qin Shen ,&nbsp;Lydia Walder ,&nbsp;Mark Burton ,&nbsp;Cara Mathews","doi":"10.1016/j.ygyno.2024.10.021","DOIUrl":"10.1016/j.ygyno.2024.10.021","url":null,"abstract":"<div><h3>Objective</h3><div>Dostarlimab in combination with carboplatin-paclitaxel (CP) improves progression-free survival in patients with primary advanced or recurrent endometrial cancer (pA/rEC), including in patients whose cancer is mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H). This study examined the cost-effectiveness of dostarlimab plus CP as a first-line treatment in the dMMR/MSI-H and overall populations.</div></div><div><h3>Methods</h3><div>A partitioned survival model with three mutually exclusive health states (progression-free disease, progressed disease, death) was developed using a US base case and a third-party payer perspective. Clinical data were from the RUBY trial and published sources. Costs were from US databases. The primary outcomes were life-years (LYs), quality-adjusted life-years (QALYs), incremental costs, and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were also performed.</div></div><div><h3>Results</h3><div>In the dMMR/MSI-H population, the model predicted gains of 6.9 LYs and 5.4 QALYs with dostarlimab plus CP compared with CP; costs were $307,696 higher with dostarlimab plus CP, resulting in an ICER of $57,151 per QALY gained. In the overall population, gains of 2.0 LYs and 1.5 QALYs were predicted with dostarlimab plus CP compared with CP; costs were $215,876 higher, resulting in an ICER of $143,783 per QALY gained. ICERs were most sensitive to the overall survival hazard ratio. At a willingness-to-pay threshold of $150,000, dostarlimab plus CP had cost-effectiveness probabilities of 100 % and 53.7 % in the dMMR/MSI-H and overall populations, respectively.</div></div><div><h3>Conclusions</h3><div>Dostarlimab plus CP is cost-effective as a treatment for the dMMR/MSI-H and overall populations of US patients with pA/rEC.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"192 ","pages":"Pages 24-31"},"PeriodicalIF":4.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of the gut microbiome with outcomes in cervical and endometrial cancer patients treated with pembrolizumab: Insights from the phase II PRIMMO trial","authors":"Emiel A. De Jaeghere ,&nbsp;Hannelore Hamerlinck ,&nbsp;Sandra Tuyaerts ,&nbsp;Lien Lippens ,&nbsp;An M.T. Van Nuffel ,&nbsp;Regina Baiden-Amissah ,&nbsp;Peter Vuylsteke ,&nbsp;Stéphanie Henry ,&nbsp;Xuan Bich Trinh ,&nbsp;Peter A. van Dam ,&nbsp;Sandrine Aspeslagh ,&nbsp;Alex De Caluwé ,&nbsp;Eline Naert ,&nbsp;Diether Lambrechts ,&nbsp;An Hendrix ,&nbsp;Olivier De Wever ,&nbsp;Koen K. Van de Vijver ,&nbsp;Frédéric Amant ,&nbsp;Katrien Vandecasteele ,&nbsp;Bruno Verhasselt ,&nbsp;Hannelore G. Denys","doi":"10.1016/j.ygyno.2024.10.020","DOIUrl":"10.1016/j.ygyno.2024.10.020","url":null,"abstract":"<div><h3>Background</h3><div>The phase II PRIMMO trial investigated a pembrolizumab-based regimen in patients with recurrent and/or metastatic cervical (CC) or endometrial (EC) carcinoma who had at least one prior line of systemic therapy. Here, exploratory studies of the gut microbiome (GM) are presented.</div></div><div><h3>Methods</h3><div>The microbial composition of 77 longitudinal fecal samples obtained from 35 patients (CC, <em>n</em> = 15; EC, <em>n</em> = 20) was characterized using <em>16S rRNA</em> gene sequencing. Analyses included assessment of alpha (Shannon index) and beta diversity (weighted UniFrac), unbiased hierarchical clustering, and linear discriminant analysis effect size. Correlative studies with demographics, disease characteristics, safety, efficacy, and immune monitoring data were performed.</div></div><div><h3>Results</h3><div>Significant enrichment in multiple bacterial taxa was associated with the occurrence or resistance to severe treatment-related adverse events (overall or gastrointestinal toxicity specifically). Consistent differences in GM taxonomic composition before pembrolizumab initiation were observed between patients with favorable efficacy (e.g., enriched with <em>Blautia</em> genus) and those with poor efficacy (e.g., enriched with <em>Enterobacteriaceae</em> family and its higher-level taxa up to the phylum level, as well as <em>Clostridium</em> genus and its <em>Clostridiaceae</em> family). Two naturally occurring GM clusters with distinct bacterial compositions were identified. These clusters showed a more than four-fold differential risk for death (hazard ratio, 4.4 [95 % confidence interval, 1.9 to 10.3], <em>P</em> &lt; 0.001) and were associated with interesting (but non-significant) trends in peripheral immune monitoring data.</div></div><div><h3>Conclusion</h3><div>Although exploratory, this study offers initial insights into the intricate interplay between the GM and clinical outcomes in patients with CC and EC treated with a pembrolizumab-based regimen.</div><div>Trial registration: <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (identifier <span><span>NCT03192059</span><svg><path></path></svg></span>) and EudraCT Registry (number 2016–001569-97).</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 275-286"},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}