Gynecologic oncology最新文献

{"title":"Understanding frailty and the role of patient-centered care for older adults with gynecologic cancer","authors":"Stephanie Cham ,&nbsp;Amanika Kumar ,&nbsp;Louise C. Walter ,&nbsp;Stuart Lichtman ,&nbsp;William P. Tew","doi":"10.1016/j.ygyno.2025.03.035","DOIUrl":"10.1016/j.ygyno.2025.03.035","url":null,"abstract":"<div><div>The number of older adults with cancer will significantly grow in the coming decades. 45 % of older adults with gynecologic cancer are estimated to be affected by frailty. Frailty is a state of reduced physiologic reserve and decreased resiliency resulting in increased vulnerability to stressors. Importantly, frailty can exist in conjunction, but is not synonymous, with chronological age and older adults can be a heterogenous population. Routine assessment of frailty can help providers prevent both over- and under-treatment. The purpose of this review to describe the current state of literature on frailty as it relates to gynecologic cancer and draw from other literature including geriatrics, medical oncology, and surgery to suggest approaches to care.</div><div>Frail patients have increased rates of surgical morbidity and mortality, higher toxicity to systemic therapy, and lower overall survival. Principles of the 5Ms (mobility, multi-complexity, mind, medications, and matters most) can be used in the clinic to guide care for older vulnerable (at risk) or frail adults. Surgical and medical oncology literature consistently indicates improved outcomes when multi-disciplinary approaches are used with routine frailty assessment. Future work is urgently needed to add validated geriatric measurements and outcomes into therapeutic trials and evaluate the impact of treatment choices on outcomes important to older adults such as functional recovery.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 42-53"},"PeriodicalIF":4.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748290","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":"MUTYH: Possibly another important gene in ovarian cancer?","authors":"Roxanna Haghighat ,&nbsp;Amanda Laterza Ozarowski ,&nbsp;Ying L. Liu ,&nbsp;Melissa K. Frey","doi":"10.1016/j.ygyno.2025.03.029","DOIUrl":"10.1016/j.ygyno.2025.03.029","url":null,"abstract":"","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 59-61"},"PeriodicalIF":4.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748415","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":"Reduced dosing of lenvatinib with pembrolizumab for advanced endometrial cancer","authors":"Quang D. Ta ,&nbsp;Connie Do ,&nbsp;Kavita Sharma ,&nbsp;Hormozan (Zan) Sorooshian ,&nbsp;Merta Cushing ,&nbsp;Nina Shah ,&nbsp;Juraj Kavecansky ,&nbsp;Michael Bookman ,&nbsp;Fang Niu ,&nbsp;Rita Hui","doi":"10.1016/j.ygyno.2025.03.034","DOIUrl":"10.1016/j.ygyno.2025.03.034","url":null,"abstract":"<div><h3>Objective</h3><div>Evaluate safety and effectiveness of reduced lenvatinib doses with pembrolizumab in patients with mismatch repair-proficient (MMRp) advanced endometrial cancer.</div></div><div><h3>Methods</h3><div>In this retrospective cohort study of lenvatinib-pembrolizumab combination therapy, patients were grouped based on initial lenvatinib dose: 20 mg daily (Group 1), less than 20 mg daily (Group 2), and 20 mg daily five days per week (Group 3). The primary outcome was six-month progression-free survival (PFS-6); safety outcomes included incidences of lenvatinib dose discontinuation or reduction due to adverse events (AEs).</div></div><div><h3>Results</h3><div>This study included 369 patients (Group 1, <em>n</em> = 204, Group 2, <em>n</em> = 154, and Group 3, <em>n</em> = 11). There was no difference in PFS-6 between Groups 1 and 2 (40.2 % vs 33.8 % respectively; <em>p</em> = 0.26) or median PFS (both 4.2 months; <em>p</em> = 0.92). A significantly higher incidence in lenvatinib dose reduction was found in Group 1 (28.1 vs 14.3 per 100 person-year; <em>p</em> &lt; 0.01). However, there was no difference in AE-related lenvatinib dose discontinuation between Groups 1 and 2 (7.2 vs 6.6 per 100 person-year, respectively; <em>p</em> = 0.61).</div></div><div><h3>Conclusion</h3><div>Full-dose lenvatinib has been associated with frequent dose modification without prospective data to guide optimization. We found no difference in PFS-6 or median PFS between starting doses of 20 mg daily versus &lt;20 mg daily in combination with pembrolizumab. Fewer dose reductions were experienced with a lower starting dose. However, no difference in dose discontinuation was observed. These findings suggest lower initial lenvatinib doses may be better tolerated without compromising effectiveness, although the lower limit of effective dosing remains to be defined.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 36-41"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740118","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":"Rethinking metformin in advanced endometrial cancer: Scientific humility, translational challenges, and the urgency for equity","authors":"Vivek Podder,&nbsp;Brian M. Slomovitz","doi":"10.1016/j.ygyno.2025.04.004","DOIUrl":"10.1016/j.ygyno.2025.04.004","url":null,"abstract":"","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages A1-A2"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844395","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":"Cemiplimab plus peltopepimut-S vaccine in recurrent cervical cancer: A phase 2 clinical trial","authors":"Domenica Lorusso ,&nbsp;Ana Oaknin ,&nbsp;Giuliano S. Borges ,&nbsp;Fernanda Damian ,&nbsp;Nelleke Ottevanger ,&nbsp;Toon Van Gorp ,&nbsp;Carlos E. Paiva ,&nbsp;Judith R. Kroep ,&nbsp;Yong-Man Kim ,&nbsp;Hee-Seung Kim ,&nbsp;Jae-Kwan Lee ,&nbsp;Hannelore Denys ,&nbsp;Roy Lalisang ,&nbsp;Andreia Cristina De Melo ,&nbsp;Andres Redondo ,&nbsp;Anna K.L. Reyners ,&nbsp;Paulo Mora ,&nbsp;Celine Closset ,&nbsp;Cornelis J.M. Melief ,&nbsp;Leon Hooftman ,&nbsp;Nicoletta Colombo","doi":"10.1016/j.ygyno.2025.03.019","DOIUrl":"10.1016/j.ygyno.2025.03.019","url":null,"abstract":"<div><h3>Objective</h3><div>To estimate the clinical benefit of cemiplimab+peltopepimut-S vaccine after disease progression on first-line chemotherapy.</div></div><div><h3>Methods</h3><div>This global phase 2 open-label study (<span><span>NCT04646005</span><svg><path></path></svg></span>) recruited patients with recurrent HPV16+ cervical cancer who had previously experienced disease progression after first-line chemotherapy. Patients received a total of 3 doses of peltopepimut-S vaccine on days 1, 29, and 50 and cemiplimab 350 mg every 3 weeks until disease progression or other reason for early discontinuation. Primary endpoint was objective response rate (ORR) per RECIST version 1.1; secondary endpoints were duration of response (DOR), overall survival (OS), progression-free survival (PFS), and safety.</div></div><div><h3>Results</h3><div>Of 113 patients enrolled between June 28, 2021 and May 22, 2023, 80.5 % were white, with a median age of 49.0 years, and 58.4 % had an ECOG PS of 0. Median duration of follow-up was 4.9 months. ORR (95 % CI) per investigator assessment was 16.8 % (9.9–23.7). ORR of patients with squamous cell carcinoma by PD-L1 expression in tumor cells was 15.8 % for patients with PD-L1 &lt; 1 % and 24.1 % for patients with PD-L1 ≥ 1 %. Median (95 % CI) DOR was 5.6 (3.5–not estimable) months. Median (95 % CI) OS and PFS were 13.3 (10.8–16.3) months and 3.0 (1.7–4.0) months, respectively. Treatment-emergent adverse events (TEAEs) occurred in 92.9 % of patients, the most common being injection-site reaction (38.9 %) and anemia (25.7 %). Six (5.3 %) patients died from a TEAE.</div></div><div><h3>Conclusion</h3><div>Cemiplimab+peltopepimut-S vaccine provides similar benefits to cemiplimab monotherapy; patients with higher PD-L1 expression in tumor cells may be more likely to benefit from treatment.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 28-35"},"PeriodicalIF":4.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705289","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":"Therapeutically targeting endometrial cancer in preclinical models by ICAM1 antibody-drug conjugates","authors":"Hanfei Xie ,&nbsp;Lu Sun ,&nbsp;Shili Yao ,&nbsp;Xuefei Tian ,&nbsp;Liming Jin ,&nbsp;Yujie Dai ,&nbsp;Yuanzheng Li ,&nbsp;Yuxuan Li ,&nbsp;Jianmin Fang ,&nbsp;Peng Guo ,&nbsp;Yingli Zhang","doi":"10.1016/j.ygyno.2025.03.027","DOIUrl":"10.1016/j.ygyno.2025.03.027","url":null,"abstract":"<div><h3>Objective</h3><div>The incidence of mortality and morbidity from endometrial cancer (EC) is increasing annually, and there is a paucity of effective targeted therapies for the condition. Antibody-drug conjugates (ADCs) represent a promising approach to tumor-targeted therapy. In this study, we aim to identify a novel molecular target for the preclinical development of EC-targeted ADCs.</div></div><div><h3>Methods</h3><div>Through quantitative and unbiased bioinformatics analyses intercellular adhesion molecule-1 (ICAM1) was identified as a potential cell membrane target. Two ADCs, ICAM1-MMAE and ICAM1-DXd, were subsequently developed by conjugating ICAM1 monoclonal antibodies with microtubule inhibitors and DNA topoisomerase inhibitors, respectively. The preclinical efficacy and biosafety of these ICAM1 ADCs were validated in both <em>in vitro</em> and <em>in vivo</em> models. Furthermore, transcriptomic analysis was conducted to elucidate the therapeutic effects of the ICAM1 ADCs.</div></div><div><h3>Results</h3><div>Quantitative flow screening and bioinformatics analyses revealed significant overexpression of ICAM1 in EC. ICAM1-MMAE and ICAM1-DXd were developed using clinically effective linkers and payloads. In preclinical models, ICAM1 ADCs showed superior antitumor efficacy compared to standard chemotherapy, achieving sustained tumor regression with an excellent safety profile in both subcutaneous and orthotopic xenograft models. Transcriptomic analysis further revealed that ICAM1-DXd potently activated tumor immunity.</div></div><div><h3>Conclusions</h3><div>ICAM1 was identified as a promising cell membrane protein target for ADC development in EC. As-synthesized ICAM1 ADCs demonstrated potent antitumor activity, favorable biosafety profiles <em>in vitro</em> and <em>in vivo</em>, and the ability to activate tumor immunity. These findings support the potential of ICAM1 ADCs as a therapeutic strategy and warrant further investigation in clinical studies.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 16-27"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705290","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":"Clinical applications of antibody drug conjugates for gynecologic malignancies: Review of available medicines and emerging therapeutics","authors":"Alyssa C. Bujnak ,&nbsp;Samantha A. Solaru ,&nbsp;Krishnansu Tewari","doi":"10.1016/j.ygyno.2025.03.013","DOIUrl":"10.1016/j.ygyno.2025.03.013","url":null,"abstract":"<div><div>With significant overall survival benefits reported in several phase 3 randomized clinical trials, the integration of anti-PD-1 immunotherapy with systemic chemotherapy has transformed the therapeutic landscape in advanced endometrial cancer and PD-L1+ recurrent/metastatic cervical cancer. For patients with FIGO stage III-IVA locally advanced cervical cancer, irrespective of PD-L1 status, chemoradiation plus pembrolizumab followed by maintenance pembrolizumab also confers a survival benefit. For newly diagnosed advanced ovarian cancer responding to primary systemic chemotherapy, maintenance therapy using PARP inhibitors and/or bevacizumab according to germline and somatic mutational analysis have been demonstrated to improve progression-free survival. Tumor heterogeneity, acquired drug resistance, and adverse events limit long-term effectiveness. Antibody-drug conjugates (ADCs) represent an innovative new class of medicines with activity in gynecologic malignancies and distinct toxicity profiles attributable to ADC construction. Adverse event mitigation strategies, biomarker discovery, and sequencing are paramount in successfully exploiting the therapeutic window provided by these novel compounds. This review discusses the application of ADCs in gynecologic cancers, including the current FDA-approved drugs mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan, as well as relevant ongoing clinical trials, including TROP2 ADCs.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 180-191"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696086","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":"Which factors predict the effectiveness of adjuvant treatment in patients with non-high-risk early-stage cervical cancer? Ancillary analysis of KGOG-1028","authors":"Junhwan Kim ,&nbsp;Jieun Jang ,&nbsp;Myong Cheol Lim ,&nbsp;Moon-Hong Kim ,&nbsp;Yun Hwan Kim ,&nbsp;Eun Seop Song ,&nbsp;Seok Ju Seong ,&nbsp;Dong Hoon Suh ,&nbsp;Jong-Min Lee ,&nbsp;Chulmin Lee ,&nbsp;Chel Hun Choi ,&nbsp;Sokbom Kang","doi":"10.1016/j.ygyno.2025.03.015","DOIUrl":"10.1016/j.ygyno.2025.03.015","url":null,"abstract":"<div><h3>Objective</h3><div>To identify predictive factors for the effectiveness of adjuvant therapy (AT) in patients with non-high-risk early-stage cervical cancer.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using data from the Korean Gynecologic Oncology Group-1028, which included 1109 low-risk and 360 intermediate-risk patients diagnosed with 2018 FIGO stage IB1-IIA cervical cancer from 2000 to 2008. Disease-free survival (DFS) according to AT was evaluated in restricted patients with certain prognostic factors, such as lymphovascular space invasion (LVSI), depth of invasion (DI) of 1/3, tumor size &gt;4 cm, or nonsquamous cell carcinoma (non-SCC). In addition to the prognostic factor of interest, clinicopathologic factors were balanced between the AT-naïve and AT groups using the inverse probability of treatment weighting.</div></div><div><h3>Results</h3><div>AT was administered to 281 (25.2 %) low-risk patients and 261 (72.5 %) intermediate-risk patients. Positive LVSI, DI of deep 1/3, tumor size &gt;4 cm, and adenocarcinoma histology were significantly prognostic when tested in the AT-naïve group. AT was effective in prolonging DFS in patients with positive LVSI (hazard ratio [HR] = 0.37; 95 % CI, 0.23–0.60), DI of deep 1/3 (HR = 0.29; 95 % CI, 0.17–0.49), and tumor size &gt;4 cm (HR = 0.28; 95 % CI, 0.11–0.70). However, AT was not effective in patients with non-SCC histology (HR = 0.69; 95 % CI, 0.41–1.16).</div></div><div><h3>Conclusions</h3><div>Patients with non-high-risk early-stage cervical cancer with any of the following conditions, including positive LVSI, DI of deep 1/3, and tumor size &gt;4 cm, can benefit from AT but not those with non-SCC histology.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 10-15"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697995","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":"ENGOT-OV16/NOVA trial of niraparib in recurrent ovarian cancer: Survival and long-term safety","authors":"Ursula A. Matulonis ,&nbsp;Jørn Herrstedt ,&nbsp;Amit Oza ,&nbsp;Sven Mahner ,&nbsp;Andrés Redondo ,&nbsp;Dominique Berton ,&nbsp;Jonathan S. Berek ,&nbsp;Charlotte A. Haslund ,&nbsp;Frederik Marmé ,&nbsp;Antonio González-Martín ,&nbsp;Stéphanie Bécourt ,&nbsp;Anna V. Tinker ,&nbsp;Jonathan A. Ledermann ,&nbsp;Benedict Benigno ,&nbsp;Gabriel Lindahl ,&nbsp;Nicoletta Colombo ,&nbsp;Izabela A. Malinowska ,&nbsp;Wenlei Liu ,&nbsp;Manjinder Bains ,&nbsp;Bradley J. Monk ,&nbsp;Mansoor R. Mirza","doi":"10.1016/j.ygyno.2025.03.018","DOIUrl":"10.1016/j.ygyno.2025.03.018","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate secondary efficacy endpoints and safety for the ENGOT-OV16/NOVA (<span><span>NCT01847274</span><svg><path></path></svg></span>) trial of niraparib maintenance therapy after extended follow-up and vital-status-data retrieval. Previously reported analyses (data cutoff, October 1, 2020) indicated benefit of niraparib maintenance therapy beyond first progression, but overall survival (OS) analyses were limited by missing data.</div></div><div><h3>Methods</h3><div>Patients were randomized 2:1 to niraparib (300 mg once daily) or placebo. A vital status check was extended to retrieve last-known-alive status for patients with missing survival data. Prespecified secondary efficacy outcomes (OS, chemotherapy-free interval [CFI], time to first subsequent therapy [TFST], PFS2, time to second subsequent therapy [TSST]) and safety are reported based on the extended data cutoff (March 31, 2021).</div></div><div><h3>Results</h3><div>Survival status was available for 97.6% (540/553) of randomized patients (germline <em>BRCA</em> [g<em>BRCA</em>]<em>-</em>mutated, 203; non-g<em>BRCA</em>–mutated, 350). Median OS with niraparib and placebo was 40.9 and 38.1 months, respectively, in the g<em>BRCA</em>-mutated cohort (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61–1.20) and 31.0 and 34.8 months, respectively, in the non-g<em>BRCA</em>–mutated cohort (HR, 1.06; 95% CI, 0.81–1.37). Medians for CFI, TFST, PFS2, and TSST numerically favored niraparib in both cohorts. No new safety signals were detected.</div></div><div><h3>Conclusions</h3><div>OS did not significantly differ between treatment arms. Prespecified secondary efficacy endpoints numerically favored niraparib. Long-term safety remained consistent with the established niraparib safety profile. Taken together with the significant improvements in PFS observed in the primary analysis, these data support a favorable overall benefit–risk profile for niraparib in the recurrent OC maintenance setting.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 192-199"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696087","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":"Comparative efficacy and safety of low-dose versus high-dose bevacizumab in ovarian cancer: An indirect treatment comparison","authors":"Josée-Lyne Ethier ,&nbsp;Cal Shephard ,&nbsp;Diana P. Granados ,&nbsp;Nikkita Dutta ,&nbsp;Rana Qadeer ,&nbsp;Saima Ahmad ,&nbsp;Ellen Kasireddy ,&nbsp;Mir-Masoud Pourrahmat ,&nbsp;Mir Sohail Fazeli","doi":"10.1016/j.ygyno.2025.03.022","DOIUrl":"10.1016/j.ygyno.2025.03.022","url":null,"abstract":"<div><h3>Objective</h3><div>First-line therapy for ovarian cancer involves cytoreductive surgery and platinum-based chemotherapy, with or without bevacizumab. Bevacizumab can be administered at low (7.5 mg/kg every three weeks [Q3W]) or high dose (15 mg/kg Q3W). This study compared the efficacy and safety of these dosing strategies.</div></div><div><h3>Methods</h3><div>Systematic literature review of Embase, MEDLINE®, and CENTRAL (18/09/2023) identified randomized controlled trials (RCTs) evaluating bevacizumab versus any therapy or control in ovarian, fallopian tube, or primary peritoneal cancer. Indirect treatment comparisons (ITC) of response, survival, and safety outcomes were performed, including sensitivity/subgroup analyses adjusting for heterogeneity.</div></div><div><h3>Results</h3><div>Six RCTs (sample size: 24–1528 patients) were included for ITC. Five evaluated high-dose bevacizumab with chemotherapy. The common comparator was carboplatin + paclitaxel. Trials mainly included stage III (<em>n</em> = 4) or stage II-III (<em>n</em> = 1) ovarian cancer patients; one did not report cancer stage. Primary analyses showed no significant differences between low- versus high-dose bevacizumab for partial response (risk ratio [95 % confidence interval]: 0.66 [0.42, 1.02]), complete response (1.76 [0.76, 4.11]), objective response rate (1.01 [0.63, 1.61]), progressive disease (1.08 [0.38, 3.10]), clinical benefit (0.89 [0.76, 1.03]), any grade ≥ 3 adverse event (1.53 [0.96, 2.44]), specific grade ≥ 3 adverse events, overall survival (hazard ratio: 0.93 [0.77, 1.13]), or progression-free survival (1.02 [0.86, 1.22]). Sensitivity and subgroup analyses confirmed findings.</div></div><div><h3>Conclusions</h3><div>This ITC found no significant difference in clinical outcomes between low- and high-dose bevacizumab combination therapy. Despite limitations of small sample size and heterogeneities, findings suggest that bevacizumab dose may not significantly impact ovarian cancer outcomes.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 1-9"},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686810","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}