Peng-Hui Wang

Programmed death-ligand 1 upregulation is associated with poor prognosis in patients with epithelial ovarian cancer

Background: The clinical significance of programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC), particularly its association with platinum resistance (PR) and prognosis, remains unclear. This study aimed to evaluate the relationship between PD-L1 expression and PR in EOC and investigate cisplatin-induced PD-L1 modulation using in vitro and in vivo models. Methods: We retrospectively analyzed 189 patients with EOC, treated between 2014 and 2020. Tumor PD-L1 expression was assessed by immunohistochemistry (IHC) using the combined positive score (CPS). Serum PD-L1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Cisplatin-induced PD-L1 regulation was examined in paired platinum-sensitive (PS: A2780 and ES2) and PR (A2780R and ES2R) cell lines and xenograft models. Results: High tumor PD-L1 expression (CPS ≥10) was more frequent in PR (38.5%) than in PS patients (19.0%, p < 0.01), and was associated with higher recurrence rates ( p < 0.001) and shorter overall survival ( p < 0.001). Serum PD-L1 concentrations were significantly elevated in patients with endometrioid and clear cell histologies compared with those in the control group ( p < 0.05). In vitro, PD-L1 expression was upregulated in PR cell lines compared with parental PS cell lines and was further increased following cisplatin exposure in a dose- and time-dependent manner. Xenograft models confirmed that cisplatin induces PD-L1 upregulation in both tumor tissue and serum, with more pronounced effects observed in PR tumors. Conclusion: PD-L1 upregulation (CPS ≥10) is associated with PR, disease recurrence, and poor prognosis in EOC. Endometrioid and clear cell histologic subtypes demonstrated higher baseline PD-L1 expression in our cohort. Cisplatin-induced PD-L1 upregulation represents a tumor-intrinsic response, particularly in PR tumor cells, highlighting PD-L1 as a histology-specific marker of poor prognosis and a potential therapeutic target in platinum-resistant EOC.

Immunology and therapeutic strategies in ovarian cancer

Epithelial ovarian cancer (OC) remains a lethal gynecologic malignancy, with approximately 70 % of patients relapsing within three years of frontline treatment. A clinically useful framework is to view advanced-stage ovarian cancer (ads-OC) as "two diseases" rather than a single uniform entity: one reflecting the classic course guided by the platinum-free interval (PF-I), and the second highlighting biologically defined subgroups where repeated relapses occur across multiple lines. This framework implies that optimal management should not be determined by PF-I alone but should be individualized using integrated disease biology and treatment context. Within these pathways, immunotherapy (IOT) has transitioned from ineffective monotherapy toward rational combination strategies designed to modulate the tumor microenvironment (TME) and overcome dominant immunosuppressive forces, such as regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Recent clinical evidence from the phase III ENGOT-ov65/KEYNOTE-B96 trial represents a historic milestone, demonstrating that the addition of pembrolizumab to weekly paclitaxel, with or without investigator-choice bevacizumab, significantly improves overall survival (OS) in patients with platinum-resistant rOC (PR-rOC) with PD-L1-expressing tumors, with OS benefit also observed in the intention-to-treat (ITT) population. These findings validate the potential of immune checkpoint inhibitor (ICI)-based regimens to reshape the therapeutic landscape in populations with substantial unmet need. Furthermore, biomarker development is moving toward a more structured framework, as proposed by SITC and NCI, emphasizing the need for standardized reporting and the exploration of emergent indicators. Institutional research further highlights that IOT-relevant biomarkers, such as PD-L1, are not fixed baseline characteristics but are dynamically upregulated by cytotoxic stress and cisplatin exposure, reflecting a compensatory immune-evasive state linked to platinum resistance. Ultimately, the management of rOC is evolving into a biologically informed, line-specific strategy that prioritizes the integration of IOT within established systemic backbones. The success of contemporary combination approaches underscores the necessity of interpreting biomarkers within a dynamic, treatment-contextualized framework. Future progress will depend on a bidirectional lab-to-trial paradigm, where mechanistic insights into treatment-induced immune modulation guide the design of precise clinical trials, ensuring that therapeutic strategies are tailored to the evolving immune context of each patient throughout the disease continuum. Beyond ICI, immune-relevant strategies targeting treatment-induced resistance pathways, exemplified by glucocorticoid receptor (GR) antagonism in the ROSELLA trial, suggest that indirect TME modulation may also yield clinically meaningful benefit in PR-rOC.

Secondary cytoreductive surgery (S-CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer: Current evidence and clinical perspectives

Recurrent epithelial ovarian cancer (rOC) remains a major therapeutic challenge because of its high relapse rate and the progressive development of chemoresistance. Secondary cytoreductive surgery (S-CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been explored as locoregional strategies to overcome the limitations of systemic therapy, but their clinical value varies substantially according to platinum sensitivity, surgical completeness, and patient selection. In platinum-sensitive rOC (PS-rOC), evidence from randomized controlled trials (RCTs) demonstrates that S-CRS provides survival benefit only when completeness of CRS (C-CRS) to CCR0 is achieved in rigorously selected patients using validated selection tools. Meta-analytic data further confirmed that incomplete resection confers little clinical advantage and may fail to offset surgical morbidity. The addition of HIPEC to S-CRS in this setting is supported by a biologically plausible rationale and has been associated with an overall survival (OS) benefit, although no consistent improvement in progression-free survival (PFS) has been demonstrated and treatment-related adverse events (TRAEs), particularly hematologic and renal AEs, are increased. These findings support a selective, center-experienced, and protocol-conscious application of HIPEC rather than routine use. In contrast, high-level evidence supporting S-CRS or S-CRS plus HIPEC in platinum-resistant rOC (PR-rOC) remains lacking. Available data are derived primarily from small retrospective series and systematic reviews with substantial heterogeneity and selection bias, precluding definitive conclusions regarding survival benefit. Several ongoing phase III RCTs are expected to clarify the optimal role, timing, and patient selection for HIPEC-based strategies across different disease settings. Overall, current evidence supports an individualized, biology-driven approach to rOC, integrating surgical feasibility, anticipated systemic treatment efficacy, and careful risk-benefit assessment within a multidisciplinary framework.

Chemoresistance in ovarian cancer (I)

Mirvetuximab soravtansine-Gynx (MIRV) for treating platinum-resistant recurrent ovarian cancer

Laparoscopic-assisted vaginal hysterectomy versus total laparoscopic hysterectomy in endometrial cancer: A retrospective cohort study

The methods of laparoscopic staging surgery (LSS) for endometrial cancer can generally be classified into two approaches: laparoscopic-assisted vaginal hysterectomy (LAVH)-based LSS and total laparoscopic hysterectomy (TLH)-based LSS. This study aims to compare perioperative and oncologic outcomes between LAVH-based LSS and TLH-based LSS. Between January 2019 to December 2024, 118 patients who underwent laparoscopic staging surgery were retrospectively observed. Patient characteristics, such as age, BMI, parity, disease extension, histology subtypes, estimated blood loss, operative time, complications and recurrence were collected and analyzed. TLH was associated with significantly lower estimated blood loss compared with LAVH (119.0 ± 69.9 vs. 218.5 ± 375.1 mL, p = 0.036). TLH also offered a tendency of shorter operative time but without significance (197.40 ± 50.74 vs. 214.41 ± 66.89 min, p = 0.135). While hospital stay, complication rate, and 30-day re-hospitalization were comparable between groups. Four recurrences were observed, all in the LAVH group. Kaplan-Meier analysis showed no significant difference in progression-free survival (p = 0.300). TLH-based LSS in early-stage EC appears a safe approach, offering reduced blood loss without compromising perioperative or oncologic outcomes compared with LAVH-based LSS.

Targeting the ST3 beta‐galactoside alpha‐2,3‐sialyltransferase 1 ( ST3Gal1 ) as a potential therapeutic strategy to overcome anti‐ VEGF resistance in endometrial cancer

Abstract Objective To investigate the role of ST3 beta‐galactoside alpha‐2,3‐sialyltransferase 1 (ST3Gal1) in endometrial cancer (EC) progression and its potential as a therapeutic target to enhance the efficacy of antiangiogenic treatment. Methods ST3Gal1 expression and its clinical relevance were analyzed in EC tissues. Functional assays evaluated its effects on vascular endothelial growth factor‐A (VEGF‐A) expression, epithelial–mesenchymal transition (EMT), and cell invasiveness. Mechanistic studies, including Duolink proximity ligation assays and co‐immunoprecipitation, examined ST3Gal1–VEGF‐A interactions. ST3Gal1 was inhibited genetically or pharmacologically using soyasaponin I (SsaI), both in vitro and in xenograft models, alone or combined with bevacizumab. Angiogenic and EMT marker expression and focal adhesion kinase (FAK)/paxillin pathway activation were assessed. Results ST3Gal1 was amplified and overexpressed in EC and correlated with advanced stage, deep myometrial invasion, and poor prognosis. It directly glycosylated VEGF‐A and activated FAK/paxillin signaling, promoting VEGF‐A expression and EMT. ST3Gal1 inhibition via SsaI reduced VEGF‐A signaling, reversed EMT marker expression, and suppressed cell migration and invasion, particularly in RL95‐2 cells. In vivo, SsaI significantly inhibited tumor growth and angiogenesis, with the most pronounced effect observed in combination with bevacizumab. Dual treatment disrupted ST3Gal1–VEGF‐A interactions and downregulated angiogenic and EMT markers. Conclusion ST3Gal1 promotes EC progression by enhancing VEGF‐A signaling and EMT via the FAK/paxillin pathway. Its inhibition improves the efficacy of antiangiogenic therapy, supporting ST3Gal1 as a promising therapeutic target to overcome anti‐VEGF‐A resistance in advanced EC.

Clinical impact of glandular involvement in high-grade squamous intraepithelial lesions of the cervix

The prognostic significance of glandular involvement in high-grade squamous intraepithelial lesions (HSIL) following cervical conization remains unclear. This research aimed to evaluate the clinical impact of glandular involvement on surgical outcomes. Between December 2019 and December 2020, 119 patients who underwent cervical conization were retrospectively observed. Patient characteristics, such as human papillomavirus (HPV) status, cytology results, glandular involvement, conization specimen depth and volume, margin status, and recurrence were collected and analyzed. Glandular involvement was significantly associated with positive endocervical margins (22.0 % vs. 6.5 %, p = 0.017), higher prevalence of preceding HSIL or CIN (cervical intraepithelial neoplasm)2/CIN3 cytology (60.4 % vs. 42.0 %), and increased HPV16 infection among high-risk HPV positive patients (69.2 % vs. 34.8 %, p = 0.050). No significant differences were observed in recurrence rates among patients with HSIL with or without glandular involvement. Multivariable analysis identified that margin status is the only independent predictor of recurrence (positive margin: OR [odds ratio] 26.85, 95 % CI [confidence interval] 2.59-277.86, p = 0.006 or uncertain margins: OR 29.90, 95 % CI 1.09-818.17, p = 0.044). While glandular involvement in HSIL is associated with positive endocervical margins, abnormal preceding cytology, and higher risk of HPV16 infection, it does not independently predict recurrence following conization. Instead, positive surgical margins are the primary factor of recurrence, highlighting the value of achieving complete excision to optimize patient outcomes.

Predictors of surgical outcomes in transcervical resection of myoma

Abstract Objective To verify identified predictors of surgical outcomes in transcervical resection of myoma (TCRM) in Filipino women. Methods A retrospective analytical cross‐sectional study was done on 474 women who underwent TCRM between 2010 and 2020, in St Luke's Medical Center, Philippines. Ethical exemption was granted by the Institutional Ethics Committee. Identified predictors of prolonged operative time (>60 min)—increased blood loss (>70 mL), fluid overload, uterine perforation, and incomplete resection—in published research studies were analyzed. Results Univariate analysis revealed that European Society for Gynecological Endoscopy (ESGE) type 2, and myoma size ≥5 cm, myoma number ≥3 were associated with prolonged operative time. ESGE type 2 and myoma size ≥5 cm were associated with increased blood loss and incomplete resection. Myoma size ≥5 cm, an intraoperative fluid deficit of 1000 mL (hypotonic) or 2500 mL (isotonic), and prolonged operative time were correlated with fluid overload. ESGE type 2 is associated with uterine perforation. Only a Lasmar score ≥5 was significantly associated with all the aforementioned unfavorable surgical outcomes. Multivariate analysis showed that a Lasmar score ≥5 (odds ratio [OR] 6143.26; 95% confidence interval [CI] 456–82 680; P  < 0.001) and myoma size ≥5 cm (OR 21.56; 95% CI 1.67–277; P  = 0.019) were independent predictors of adverse surgical outcomes. Conclusion This study verified that the Lasmar classification can predict TCRM complexity with cut‐off values of 5 for both Lasmar score and myoma size. We recommend that the use of the Lasmar scoring classification preoperatively may be beneficial in TCRM in Filipino women.

Identification of vascular hotspots and analysis of micro‐vessel flow velocity waveforms in high‐grade squamous intraepithelial lesions of the cervix

AbstractObjectivesTo assess hotspot micro‐vessel flow velocity waveforms in human papillomavirus (HPV) cervical infections using transvaginal power Doppler ultrasound (TV‐PDU) and explore associations with high‐grade squamous intraepithelial lesions (HSIL, cervical intraepithelial neoplasia [CIN] II and III).MethodsIn all, 62 patients with confirmed HPV‐HSIL (14 CIN II, 48 CIN III) and 65 age‐ and parity‐matched women with neither HPV infection nor CIN were compared. Seven parameters by TV‐PDU were used to assess vascular classification and micro‐vessel flow velocity, including vascular grading (class I, II, III), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end‐diastolic velocity (ED), time average maximum velocity (TAMV), and the vascular index (VI = PS/ED).ResultsHSIL was primarily associated with vascular class I (75.8%), followed by class II (14.5%) and class III (9.7%). PI, RI, and VI in HSIL were significantly lower than the control group (P < 0.0001). Mean PI, RI, and VI values decreased progressively from the normal cervix to CIN II–III. At a PI cutoff of 1.03, sensitivity was 88.7%, specificity was 83.8%, and area under the curve (AUC) was 95.0. At an RI cutoff of 0.68, sensitivity was 96.8%, specificity 61.5%, and AUC 84.0. At a VI cutoff of 2.84, sensitivity was 85.5%, specificity 78.5%, and AUC 85.0.ConclusionBased on different patterns of hotspot vascular classification and micro‐vessel flow velocity waveforms, particularly PI between HSIL and the normal cervix, TV‐PDU may offer a potential role for aiding the planning for patients with suspicious HSIL. Further studies are needed to validate the findings.

Bevacizumab is associated with a higher gastrointestinal/genitourinary fistula or perforation risk in cervical cancer patients undergoing pelvic radiotherapy

Abstract Background Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer. Objectives To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients. Search Strategy In this meta‐analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022. Selection Criteria Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients. Data Collection and Analysis Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test ( I 2 ) was used to assess heterogeneity. Egger's regression test with a two‐tailed P value was used to evaluate publication bias. Main Results Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 [95% CI: 1.76–9.20] and OR 4.71 [95% CI: 1.51–14.70], respectively). Conclusions The bevacizumab‐containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab‐associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits.

Functional Gene Clusters in Global Pathogenesis of Clear Cell Carcinoma of the Ovary Discovered by Integrated Analysis of Transcriptomes

Clear cell carcinoma of the ovary (ovarian clear cell carcinoma (OCCC)) is one epithelial ovarian carcinoma that is known to have a poor prognosis and a tendency for being refractory to treatment due to unclear pathogenesis. Published investigations of OCCC have mainly focused only on individual genes and lack of systematic integrated research to analyze the pathogenesis of OCCC in a genome-wide perspective. Thus, we conducted an integrated analysis using transcriptome datasets from a public domain database to determine genes that may be implicated in the pathogenesis involved in OCCC carcinogenesis. We used the data obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) DataSets. We found six interactive functional gene clusters in the pathogenesis network of OCCC, including ribosomal protein, eukaryotic translation initiation factors, lactate, prostaglandin, proteasome, and insulin-like growth factor. This finding from our integrated analysis affords us a global understanding of the interactive network of OCCC pathogenesis.

The Potential Role of Complement System in the Progression of Ovarian Clear Cell Carcinoma Inferred from the Gene Ontology-Based Immunofunctionome Analysis

Ovarian clear cell carcinoma (OCCC) is the second most common epithelial ovarian carcinoma (EOC). It is refractory to chemotherapy with a worse prognosis after the preliminary optimal debulking operation, such that the treatment of OCCC remains a challenge. OCCC is believed to evolve from endometriosis, a chronic immune/inflammation-related disease, so that immunotherapy may be a potential alternative treatment. Here, gene set-based analysis was used to investigate the immunofunctionomes of OCCC in early and advanced stages. Quantified biological functions defined by 5917 Gene Ontology (GO) terms downloaded from the Gene Expression Omnibus (GEO) database were used. DNA microarray gene expression profiles were used to convert 85 OCCCs and 136 normal controls into to the functionome. Relevant offspring were as extracted and the immunofunctionomes were rebuilt at different stages by machine learning. Several dysregulated pathogenic functions were found to coexist in the immunopathogenesis of early and advanced OCCC, wherein the complement-activation-alternative-pathway may be the headmost dysfunctional immunological pathway in duality for carcinogenesis at all OCCC stages. Several immunological genes involved in the complement system had dual influences on patients’ survival, and immunohistochemistrical analysis implied the higher expression of C3a receptor (C3aR) and C5a receptor (C5aR) levels in OCCC than in controls.

Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer

The use of weekly chemotherapy for the treatment of patients with advanced-stage serous-type epithelial Tubo-ovarian cancer (ETOC), and primary peritoneal serous carcinoma (PPSC) is acceptable as the front-line postoperative chemotherapy after primary cytoreductive surgery (PCS). The main component of dose-dense chemotherapy is weekly paclitaxel (80 mg/m2), but it would be interesting to know what is the difference between combination of triweekly cisplatin (20 mg/m2) or triweekly carboplatin (carboplatin area under the curve 5-7 mg/mL per min [AUC 5-7]) in the dose-dense paclitaxel regimen. Therefore, we compared the outcomes of women with Gynecology and Obstetrics (FIGO) stage IIIC ETOC and PPSC treated with PCS and a subsequent combination of dose-dense weekly paclitaxel and triweekly cisplatin (paclitaxel–cisplatin) or triweekly carboplatin using AUC 5 (paclitaxel–carboplatin). Between January 2010 and December 2016, 40 women with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC EOC, FTC, or PPSC were enrolled, including 18 treated with paclitaxel–cisplatin and the remaining 22 treated with paclitaxel–carboplatin. There were no statistically significant differences in disease characteristics of patients between two groups. Outcomes in paclitaxel–cisplatin group seemed to be little better than those in paclitaxel–carboplatin (median progression-free survival [PFS] 30 versus 25 months as well as median overall survival [OS] 58.5 versus 55.0 months); however, neither reached a statistically significant difference. In terms of adverse events (AEs), patients in paclitaxel–carboplatin group had more AEs, with a higher risk of neutropenia and grade 3/4 neutropenia, and the need for a longer period to complete the front-line chemotherapy, and the latter was associated with worse outcome for patients. We found that a period between the first-time chemotherapy to the last dose (6 cycles) of chemotherapy >21 weeks was associated with a worse prognosis in patients compared to that ≤21 weeks, with hazard ratio (HR) of 81.24 for PFS and 9.57 for OS. As predicted, suboptimal debulking surgery (>1 cm) also contributed to a worse outcome than optimal debulking surgery (≤1 cm) with HR of 14.38 for PFS and 11.83 for OS. Based on the aforementioned findings, both regimens were feasible and effective, but maximal efforts should be made to achieve optimal debulking surgery and following the on-schedule administration of dose-dense weekly paclitaxel plus triweekly platinum compounds. Randomized trials validating the findings are warranted.

Managing the transition in cervical screening methods for Taiwan: Policy recommendations and perspectives

Since government-provided annual cervical cytology testing for all Taiwanese women aged 30 years or older became available in 1995, both cervical cancer incidence and death have decreased significantly. However, with the 2018 introduction of the national immunization program for human papillomavirus (HPV) vaccination in all schoolgirls aged 13-15 years old, the positive predictive value of cytology testing is expected to decrease with rising vaccination rates, and therefore a transition to more sensitive HPV-based testing may be needed. This position paper, derived from discussions by a panel of experts in cervical cancer screening, provides short-, medium-, and long-term policy recommendations to manage the transition between cervical screening methods for Taiwan. The recommendations include concrete suggestions regarding testing procedures, standards, accreditation, monitoring, promotion, and implementation. It is hoped that comprehensive preparation and management of this transition will enable Taiwan to repeat the previous successes of the cervical cytology testing program.

First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial

PURPOSE Lenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) in the phase III Study 309/KEYNOTE-775. We report results from the phase III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101 ) that evaluated len + pembro versus chemotherapy in first-line aEC. METHODS Patients with stage III to IV or recurrent, radiographically apparent EC and no previous chemotherapy or disease progression ≥6 months after neo/adjuvant platinum-based chemotherapy were randomly assigned 1:1 to lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks or paclitaxel 175 mg/m 2 plus carboplatin AUC 6 mg/mL/min once every 3 weeks. Primary end points were PFS and OS, evaluated in the mismatch repair-proficient (pMMR) and all-comers populations. Noninferiority was assessed for OS at final analysis (FA) for len + pembro versus chemotherapy (multiplicity-adjusted, one-sided nominal alpha, .0159; null hypothesis–tested hazard ratio [HR], 1.1). RESULTS Eight hundred forty-two patients were randomly assigned (len + pembro, n = 420 [pMMR population, n = 320]; chemotherapy, n = 422 [pMMR population, n = 322]). At FA (data cutoff, October 2, 2023), median PFS (95% CI) in the pMMR population was 9.6 (8.2 to 11.9) versus 10.2 (8.4 to 10.5) months with len + pembro versus chemotherapy (hazard ratio [HR], 0.99 [95% CI, 0.82 to 1.21]) and among all-comers was 12.5 (10.3 to 15.1) versus 10.2 (8.4 to 10.4) months (HR, 0.91 [95% CI, 0.76 to 1.09]; descriptive analyses). Median OS (95% CI) in the pMMR population was 30.9 (25.4 to 37.7) versus 29.4 (26.2 to 35.4) months with len + pembro versus chemotherapy (HR, 1.02 [95% CI, 0.83 to 1.26]; noninferiority P = .246, not statistically significant per multiplicity control strategy) and among all-comers was 37.7 (32.2 to 43.6) versus 32.1 (27.2 to 35.7) months (HR, 0.93 [95% CI, 0.77 to 1.12]). Grade ≥3 treatment-related adverse events occurred in 331/420 (79%) versus 274/411 (67%) treated patients. CONCLUSION First-line len + pembro did not meet prespecified statistical criteria for PFS or OS versus chemotherapy in pMMR aEC.

Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician’s choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer

In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1-43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49-1.10) and 0.64 (0.44-0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45-1.02) and 0.61 (0.41-0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3-5, 74% and 72%), respectively. Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC. ClinicalTrials.gov Identifier: NCT03517449.

Nab-paclitaxel Versus Sb-taxanes As First-Line Treatment in Advanced Ovarian Cancer

The purpose of this study is to compare the efficacy and safety of nab-paclitaxel with solvent-based taxanes as first-line treatment for patients with advanced primary epithelial ovarian cancer (EOC), primary peritoneal carcinoma or fallopian tube carcinoma.