Chyong-Huey Lai

Combined targeting poly (ADP-ribose) polymerase and receptor tyrosine kinase inhibits ovarian clear cell carcinoma progression through disrupted ribosome biogenesis

Molecular profiling reveals novel therapeutic targets and clonal evolution in ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) has a disproportionately high incidence among women in East Asia. Patients diagnosed with OCCC tend to experience worse clinical outcomes than those with high-grade serous carcinoma (HGSC) at advanced stages. The unfavorable prognosis of OCCC can be partly attributed to its frequent resistance to conventional chemotherapy. Within a precision medicine framework, we sought to provide a comprehensive molecular characterization of OCCC using whole-exome sequencing to uncover potential molecular targets that may inform novel therapeutic strategies. We performed whole-exome sequencing analysis on tumor-normal paired samples from 102 OCCC patients. This comprehensive genomic characterization of a substantial cohort of OCCC specimens was coupled with an analysis of clonal progression. On analyzing 102 OCCC samples, ARID1A (67%) and PIK3CA (49%) emerged as the most frequently mutated driver genes. We identified tier 1 or 2 clinically actionable molecular targets in 40% of cases. This included DNA mismatch repair deficiency (n = 1), as well as BRCA2 (n = 1), PIK3CA (n = 36), KRAS Our study provides a comprehensive characterization of the genomic landscape and clonal evolution in OCCC within a substantial cohort. These findings unveil potentially actionable molecular alterations that could be leveraged to develop targeted therapies.

Comparison of immediate germline sequencing and multi-step screening for Lynch syndrome detection in high-risk endometrial and colorectal cancer patients

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome with a significantly increased risk of colorectal and endometrial cancers. Current standard practice involves universal screening for LS in patients with newly diagnosed colorectal or endometrial cancer using a multi-step screening protocol (MSP). However, MSP may not always accurately identify LS cases. To address this limitation, we compared the diagnostic performance of immediate germline sequencing (IGS) with MSP in a high-risk group. A total of 31 Taiwanese women with synchronous or metachronous endometrial and colorectal malignancies underwent MSP which included immunohistochemical staining of DNA mismatch repair (MMR) proteins, Our findings indicate that IGS surpassed MSP in terms of diagnostic yield (29.0% vs. 19.4%, respectively) and sensitivity (90% vs. 60%, respectively). Specifically, IGS successfully identified nine LS cases, which is 50% more than the number detected through MSP. Additionally, germline methylation analysis revealed one more LS case with constitutional Our study suggests that IGS may potentially offer a more effective approach compared to MSP in identifying LS among high-risk patients. This advantage is evident when patients have been pre-selected utilizing specific clinical criteria.

Distinct genomic subgroups and mutational patterns in undifferentiated/dedifferentiated endometrial carcinoma

Endometrial cancer represents a significant global health challenge, with undifferentiated and dedifferentiated endometrial carcinoma (UDEC) being a particularly aggressive subset. We employed whole-exome sequencing (WES) to comprehensively characterize the molecular landscape of 29 UDECs in a single institution cohort. We analyzed driver mutations, molecular subgroups, SWI/SNF complex, DNA mismatch repair (MMR) pathways, and somatic copy number alterations (SCNAs). We identified 5 (17%) ultramutated tumors, 14 (48%) DNA mismatch repair (MMR)-deficient tumors, and 10 (35%) mutation-low tumors in this cohort. Mutations in the SWI/SNF family and other driver genes are common, including PTEN, ARID1A, KMT2B, ARID1B, SMARCA4, and PIK3CA. Genomic inactivation of SWI/SNF complex genes occurred in 19 of 29 (66%) of cases, highlighting the frequent chromatin remodeling dysfunction in UDEC. We observed frequent homopolymer mutations in UDECs with MMR deficiency, with RPL22 Our analysis revealed distinct architectures and actionable alterations in UDEC. The identification of molecular subgroups provides a promising framework for prognostic stratification. Collectively, our findings not only advance our understanding of UDEC biology but also illuminate potential translational applications.

Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent endometrial carcinoma: the Asian cohort of the AtTEnd/ENGOT-EN7 trial

This post-hoc analysis of the AtTEnd trial explored differences in the prognostic characteristics and in the efficacy of atezolizumab between Asians and non-Asians. The role of Asian race was evaluated on progression-free survival (PFS) using Cox-models and on time to appearance of new lesions using Fine and Gray models. From October 2018 to February 2022, 549 patients were randomized, of whom, 20.4% were Asian. Asians showed a better prognostic profile in terms of age, body mass index, Eastern Cooperative Oncology Group performance status, disease status and previous treatments. The prognostic impact of Asian race on PFS was confirmed in the placebo arm (adjusted hazard ratio [HR]=0.41; 95% confidence interval [CI]=0.24-0.70). In proficient mismatch repair (pMMR) tumors, the HRs for PFS comparing atezolizumab versus placebo were 0.82 (95% CI=0.63-1.05) in non-Asians, and 1.42 (95% CI=0.80-2.50) in Asians. In the pMMR population randomized to atezolizumab, the subdistribution HRs comparing Asians to non-Asians were 0.68 (95% CI=0.43-1.09) for progression with new lesions and 1.21 (95% CI=0.73-2.03) for progression without new lesions. Asians showed a higher occurrence of severe adverse events in atezolizumab compared to placebo arm (Asians: 82.1% vs. 64.3%, p=0.036; non-Asian: 63.3% vs. 63.6%, p=0.949). Race seems to affect the safety of the addition of atezolizumab and, in pMMR tumors, also its efficacy. In the atezolizumab arm, Asian patients seem to have a lower cumulative incidence of new lesions when primary tumor regrowth was considered a competing risk, and a higher cumulative incidence of primary tumor regrowth when new lesions appearance was the competing risk. ClinicalTrials.gov Identifier: NCT03603184.

Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice

Endometrial cancer (EC) is one of the most common gynecologic cancers worldwide. There were 417,367 newly diagnosed cases and 97,370 deaths due to this disease worldwide in 2020. The incidence rates have increased over time, especially in countries with rapid socioeconomic transitions, and EC has been the most prevalent gynecologic malignancy in Taiwan since 2012. The new EC molecular classifications of The Cancer Genome Atlas (TCGA) Research Network include clear-cell carcinoma, serous carcinoma, and carcinosarcoma, while undifferentiated/dedifferentiated EC (UDEC) is not mentioned, and most previous clinical trials for EC have not included UDEC. UDEC is rare, has an aggressive growth pattern, tends to be diagnosed at an advanced stage, and is resistant to conventional chemotherapy. In this review, case series or case reports on the clinical features and genomic/epigenetic and expression profiles on UDEC data are summarized in order to identify potential molecular targets for current and future research.

Nucleophosmin/B23 promotes endometrial cancer cell escape from macrophage phagocytosis by increasing CD24 expression

Despite recent therapeutic breakthroughs, advanced and/or recurrent endometrial cancer still poses a significant health burden globally. While immunotherapy can theoretically lead to durable responses, the benefits to patients remain limited. In an effort to identify novel immunotherapeutic targets, we specifically focused on the potential role of nucleophosmin (NPM, also known as B23) - a nucleolar phosphoprotein involved in tumorigenesis - in cancer immune evasion. Expression profiling with oligonucleotide microarrays was conducted to identify differentially expressed genes in NPM/B23-silenced endometrial cancer cells. CD24 - a heat-stable antigen commonly overexpressed in solid tumors and a target for cancer immunotherapy - was identified as one of the key NPM/B23-regulated molecules. We found that NPM/B23 was capable of inducing CD24 expression, with the Sp1 binding site in the CD24 promoter being essential for NPM/B23-mediated transcriptional activation. Interestingly, NPM/B23 silencing in endometrial cancer cells enhanced phagocytic removal by macrophages through a decreased exposure of CD24 on the cell surface. Conversely, restoration of CD24 expression in NPM/B23-silenced endometrial cancer cells inhibited macrophage-mediated phagocytosis. These results indicate that NPM/B23-driven CD24 overexpression enables endometrial cancer cells to evade from phagocytosis. We further suggest that CD24 may serve as a novel target for endometrial cancer immunotherapy. KEY MESSAGES: NPM/B23 induced CD24 expression in endometrial tumorigenesis. Sp1 binding site in the CD24 promoter is essential for the activation. NPM/B23 silencing enhanced phagocytosis by macrophages through decrease of CD24 on cancer cells. Restoration of CD24 expression in NPM/B23-silenced cancer cells inhibited macrophage-mediated phagocytosis.

Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT)

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Comparison of outcomes of laparotomic and minimally invasive radical hysterectomy in women with early-stage cervical cancer

This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer. The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables. Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH. After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively. The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group. After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.

BRCA1/2mutation status in patients with metachronous breast and ovarian malignancies: clues towards the implementation of genetic counseling

The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent Our results provide pilot evidence that

Postoperative adjuvant dose-dense chemotherapy with bevacizumab and maintenance bevacizumab after neoadjuvant chemotherapy for advanced ovarian cancer: A phase II AGOG/TGOG trial

The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer. This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3-4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80 mg/m Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1 st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95 % confidence interval [CI], 13.7-30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 33.8-64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively. This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout.

Human papillomavirus prevalence, genotype distribution, and prognostic factors of vaginal cancer

AbstractWe aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I‐Lan, Taiwan) and E6 type‐specific‐PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non‐SCC. The median follow‐up time was 134.3 months (range 0.9–273.4). Among nine initially HPV‐negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole‐genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non‐SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5‐year cancer‐specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16‐ and HPV‐positivity, LN metastasis and stage), were included in models 2–5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64–4.56) and LN metastasis (HR = 2.81–3.44) were significant negative predictors of CSS, whereas p16‐positivity (HR = 0.29–0.32) and HPV‐positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV‐positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16‐ and HPV‐positivity were significantly associated with better prognosis.

Role of human papillomavirus status after conization for high‐grade cervical intraepithelial neoplasia

AbstractHuman papillomavirus (HPV) is the well‐established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high‐grade cervical intraepithelial neoplasia (HG‐CIN). We conducted an observational study for long‐term outcomes and HPV genotype changes after conization for HG‐CIN. Between 2008 and 2014, patients with newly diagnosed HG‐CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG‐CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non‐surveillance (non‐S) group. For the S group (n = 493), the median follow‐up period was 74.3 months. Eighty‐four cases had recurrent CIN Grade 2 or worse (CIN2+) (5‐year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type‐specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9‐valent vaccine types. Among the 7397 non‐S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non‐S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type‐specific HPV infections, effective therapeutic vaccines are an unmet medical need.

Inhibition of BIRC2 Sensitizes α7-HPV-Related Cervical Squamous Cell Carcinoma to Chemotherapy

The α7-human papillomavirus (HPV)-related cervical squamous cell carcinoma (SCC) is associated with poor prognosis. We compared the genomic profiles of this disease in a cohort corresponding to the 2001–2014 period with various responses to radiotherapy or concurrent chemoradiation through microRNA (miR) profiling involving miR 4.0 array and human transcriptome array 2.0 analyses. A real-time quantitative polymerase chain reaction was then conducted to identify the predictive biomarkers. A significantly lower expression of miR143-3p in recurrent tumors (p = 0.0309) relative to that in nonrecurrent tumors was observed. The miR143-3p targeted the mRNA expression of the baculoviral inhibitor of the apoptosis protein (IAP) repeat-containing 2 (BIRC2; p = 0.0261). The BIRC2 protein levels (p = 0.0023) were significantly higher in recurrent tumors than in nonrecurrent tumors. Moreover, the miR-143-3p sensitized the response of α7-HPV-related cervical SCC to chemotherapy by targeting BIRC2. A combination of BIRC2-inhibitor LCL161 and topotecan exerted synergistic effects on cancer cells and animal tumor models. In a pooled cohort of α7-HPV-related cervical SCC (including mixed infections with non-α7-HPV) treated between 1993 and 2014, high BIRC2 expression was associated with significantly worse outcomes (cancer-specific survival, hazard ratio (HR) = 1.42, p = 0.008; progression-free survival, HR = 1.64; p = 0.005). Summarily, BIRC2 constitutes a novel prognostic factor and therapeutic target for α7-HPV-related cervical SCC.

East Asian Gynecologic Oncology Trial Group (EAGOT): founding history and future perspective

Racial and regional differences exist in morbidity, histology, drug response, toxicity, and prognosis of gynecologic cancer. However, most large-scale phase III studies have been conducted in Western countries, and these data on Asians, who account for more than half of the world's population, are limited. To build a global clinical trial network in Asia, four clinical trial groups with high expertise and international competitiveness in East Asia, namely the Japanese Gynecologic Oncology Group in Japan, the Korean Gynecologic Oncology Group in Korea, the Taiwanese Gynecologic Oncology Group in Taiwan, and the Chinese Gynecologic Cancer Society in the People's Republic of China, established a new group called the East Asia Gynecologic Oncology Trial Group (EAGOT) on November 19, 2021. It includes four committees: the Cervical Cancer Committee, Uterine Corpus Cancer Committee, Ovarian Cancer Committee, and Translational Research Committee. The purpose of EAGOT is to conduct international clinical trials in an effort to provide the best treatments for Asian women affected by gynecologic cancer. Discussions on new collaborative clinical trials have already begun. The first Annual EAGOT Meeting was held on May 25-27, 2023 in Niigata, Japan. EAGOT, the largest healthcare/investigational innovation network in Asia in the area of gynecologic cancers, will become a platform for establishing standards of care and lead to guidelines for Asian women suffering from gynecologic cancer. The harmonization of regulatory/investigator-initiated clinical trials, simultaneous approval of unapproved drugs in the four countries under a common protocol, and expansion of indications will improve the prognosis of gynecologic cancers in Asia in the near future.

Clinical factor‐based risk stratification for precision therapy in locally advanced squamous cell carcinoma of the uterine cervix

AbstractBackgroundConcurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. In this study, we analyzed the pretreatment clinical and 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) characteristics of patients with locally advanced cervical squamous cell carcinoma (SCC) to develop a scoring prototype for risk stratification.MethodsTwo cohorts were constructed in this study. Cohort 1 comprised patients with cervical SCC with 2009 FIGO stage III‐IVA or stage I–II with positive pelvic or para‐aortic lymph node (PALN) on PET/CT from AGOG09‐001 trial. Cohort 2 comprised patients with similar characteristics who had received adequate therapy in our hospital between 2016 and 2021. Pretreatment patient characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of primary tumor and nodal SUVmax were assessed for cancer‐specific survival (CSS) using multivariate Cox regression.ResultsAnalysis of combined data from cohorts 1 (n = 55) and 2 (n = 128) indicated age ≥ 66 years, primary tumor MTV ≥87 mL, and positive PALN on PET/CT to be independently significant adverse predictors for CSS (p &lt; 0.001, p = 0.014, and p = 0.026, respectively) with a median follow‐up duration of 51 months. Assigning a score of 1 to each adverse predictor, patients with cumulative risk scores of 0, 1, 2, and 3 were discovered to have a 5‐year CSS of 86.9%, 71.0%, 32.2%, and 0%, respectively (p &lt; 0.001).ConclusionAge, primary tumor MTV, and positive PALN on PET/CT may serve as independent predictors of poor survival in patients with locally advanced cervical SCC. Our findings indicate that patients without any adverse factors can receive standard CCRT, whereas those with at least one adverse factor can consider novel combination therapies or clinical trials.

Metastatic Cervical Cancer in the Asia-Pacific Region: Current Treatment Landscape and Barriers

Abstract Despite treatment advances for metastatic cervical cancer (mCC), the Asia-Pacific region faces significant barriers in treatment accessibility, availability, and healthcare infrastructure. This study explored the treatment landscape and barriers for mCC in the Asia-Pacific. A descriptive, cross-sectional, web-based study evaluating cervical cancer treatment patterns was conducted among medical, radiation, and gynecologic oncologists and gynecologists in the Chinese mainland (n = 80), Australia, the Philippines, South Korea, and Taiwan (n = 20 each). Eligible respondents were primarily involved in direct patient care (≥60%) and were key treatment deciders with ≥5 years of experience. Among patients with cervical cancer of 160 physicians, 10.9% had metastatic disease, of which 50.3% were aged 41 to 60 years and had Eastern Cooperative Oncology Group scores of 0 to 2 (78.7%). Top treatment modalities included systemic therapy (ST) alone (43.6%) and radiotherapy + ST (33.4%). Top first-line regimens were carboplatin/cisplatin + paclitaxel ± bevacizumab (42.3% and 33.1%, respectively), and the top second-line treatment regimens were carboplatin + paclitaxel + bevacizumab (12.0%) and cisplatin + paclitaxel + bevacizumab (11.5%). PD-L1 testing was more common in South Korea (80.8%) than in the Chinese mainland (48.8%) and Taiwan (26.4%). Treatment drivers included National Comprehensive Cancer Network guidelines (82.7%), disease stage (87.4%), Eastern Cooperative Oncology Group status (83.5%), comorbidities (59.1%), drug efficacy (88.2%), safety (84.3%), and accessibility (66.9%). Treatment challenges included poor prognosis (26.8%), patient affordability (21.3%), and limited treatment option availability (19.7%). In bevacizumab-reimbursed locations, patient tolerability and insufficient medical resources persisted. In conclusion, approximately 11% of cervical cancer cases were metastatic. Treatment preferences were radiotherapy and ST, with funding, cost, accessibility, and availability challenges. Policies supporting reimbursement and accessibility could encourage the adoption of effective alternative therapies. Significance: The findings offer valuable insights about current treatments and the related unmet needs in funding, cost, accessibility, and availability across the Asia-Pacific region. These further highlight areas of importance and the need for implementing reimbursement policies and enhancing accessibility to support the adoption of effective, advanced treatments.

Pan-Asia adapted ESMO Clinical Practice Guideline for the management of patients with newly diagnosed and relapsed epithelial ovarian cancer

The European Society for Medical Oncology (ESMO) Clinical Practice Guideline for the diagnosis, treatment and follow-up of patients with newly diagnosed and relapsed epithelial ovarian cancer (EOC), published in 2023, was adapted in July 2024, according to established standard methodology, to produce the Pan-Asian adapted ESMO consensus guideline for the management of Asian patients with EOC. The adapted guideline presented in this manuscript represents the consensus opinions reached by a panel of Asian experts in the treatment of patients with EOC representing the oncological societies of China, Indonesia, India, Japan, Korea, Malaysia, the Philippines, Singapore, Taiwan and Thailand, coordinated by ESMO and the Indian Society of Medical and Pediatric Oncology. Voting was based on scientific evidence and was independent of current treatment practices, drug access restrictions and reimbursement decisions in the represented countries. Drug access and reimbursement across Asia are discussed separately in the manuscript. The Pan-Asian consensus aims to guide the optimisation and harmonisation of management of patients with EOC in Asia, drawing on the evidence provided by both Western and Asian trials. Attention is drawn to the disparity in the drug approvals and reimbursement strategies between countries.

Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors

Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877 ) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.

Consistency in human papillomavirus type detection between self‐collected vaginal specimens and physician‐sampled cervical specimens

AbstractWith the rising need for accessible cervical cancer screening, self‐sampling methods offer a promising alternative to traditional physician‐led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high‐risk HPV (hrHPV) types between samples collected by physicians and those self‐collected by women using a self‐sampling kit for validation. Women aged 21–65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician‐sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self‐sampling kit closely matched the physician‐led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72–0.79; agreement: 87.7%, 95% CI: 85.8–89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72–0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user‐friendly alternative to traditional sampling methods. This suggests that self‐sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

Atezolizumab Trial in Endometrial Cancer - AtTEnd

Atezolizumab is an engineered humanised monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. In May 2016 atezolizumab was approved by the FDA for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant); in October 2016 it was approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities. Finally, in April 2017 atezolizumab was granted accelerated approval by FDA for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy. Combinations of atezolizumab with chemotherapeutic agents and/or targeted therapies were studied in different solid tumors such as melanoma, NSCLC, renal cell carcinoma and colorectal carcinoma. From these studies the AE profile of atezolizumab combinations were consistent with that of the individual agents. Finally, preliminary results of a Phase Ia study of Atezolizumab (NCT01375842) monotherapy in relapsed endometrial cancer were reported as abstract at ASCO 2017. Fifteen patients were evaluated for safety and efficacy with a minimum follow-up of 11.2 months. No G4-5 related AEs occurred. Regarding efficacy ORR was 13% \[2/15\] by RECIST. Atezolizumab seemed to have a favorable safety profile, with durable clinical benefit in some patients. Further studies with atezolizumab are warranted given its promising results in advanced endometrial cancer and the limited efficacy of current treatment options.