Search

Purpose: The relationship between treatment outcomes, alteration of the expression of biological markers, and tumor volume response during radiotherapy (RT) in patients with uterine cervical cancer was analyzed. Materials and Methods: Twenty patients with cervical squamous cell carcinoma received definitive RT with (n = 17) or without (n = 3) concurrent chemotherapy. Tumor volumes were measured by three serial magnetic resonance imaging scans at pre-, mid-, and post-RT. Two serial punch biopsies were performed at pre- and mid-RT, and immunohistochemical staining for cyclooxygenase (COX)-2 and epidermal growth factor receptor was performed. The median follow-up duration was 60 months. Results: The median tumor volume response at mid-RT (V2R) was 0.396 (range, 0.136 to 0.983). At mid-RT, an interval increase in the distribution of immunoreactivity for COX-2 was observed in 8 patients, and 6 of them showed poor mid-RT tumor volume response (V2R ≥ 0.4). Four (20%) patients experienced disease progression after 10 to 12 months (median, 11 months). All 4 patients had poor mid-RT tumor volume response (p = 0.0867) and 3 of them had an interval increase in COX-2 expression. Overall survival (OS) and progression-free survival (PFS) decreased in patients with V2R ≥ 0.4 (p = 0.0291 for both). An interval increase in COX-2 expression at mid-RT was also associated with a decreased survival (p = 0.1878 and 0.1845 for OS and PFS, respectively). Conclusion: Poor tumor volume response and an interval increase in COX-2 expression at mid-RT decreased survival outcomes in patients with uterine cervical cancer. [ABSTRACT FROM AUTHOR]

Aim: To evaluate prognostic factors in Korean patients with endometrial cancer. Methods: A retrospective analysis was conducted on 248 patients who were staged surgically at the Samsung Medical Center between 1995 and 2004. Survival data were analyzed using Kaplan Mcicr estimates, and multivariate analysis was performed using the Cox regression method. Results: The median age was 51 years (range 21-75), which was younger than in previous studies in Western patients, and the age of 50 years was the cutoff to predict survival. More than half (55.6%) were normal weight or underweight (BMI <25). Multivariate analysis revealed that age, Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage, and histopathology were independent predictors of disease-free survival, and FIGO stage and p53 mutation were independent prognostic factors for disease-specific survival (DSS). The 5-year DSS for patients with stage I, II, III and IV disease was 95.6,93.8,69.8 and 50%, respectively. The 5-year DSS rate for patients with a p53 mutation was 84.4%, compared with 97.1% for patients without. Conclusions: Korean patients with endometrial cancer were younger and had a lower BMI than previously reported. Furthermore, age greater than 50 years was predictive of a poor outcome. Age, FIGO stage, histopathology and a p53 mutation were independent prognostic factors for survival. [ABSTRACT FROM AUTHOR]

Objective: To compare survival outcomes and treatment-related morbidities between radical hysterectomy (RH) and primary chemoradiation therapy (CRT) in patients with bulky early-stage cervical cancer. Methods: We selected 215 patients with stage IB2 and IIA2 cervical cancer (tumor diameter > 4 cm on magnetic resonance imaging) who underwent RH followed by tailored adjuvant therapy (n=147) or primary CRT (n=68) at two tertiary referral centers between 2001 and 2010. Results: About twenty nine percent of patients were cured by RH alone and these patients experienced the best survival outcomes with the lowest morbidity rates. After the median follow-up times of 40 months, 27 RH (18.4%) and 20 CRT (29.4%) patients had recurrence (p=0.068) and 23 (15.6%) and 17 (25%) patients died of disease (p=0.101). The 5-year progression-free survival were 77% and 66% (p=0.047), and the 5-year overall survival were 78% and 67% (p=0.048) after RH and primary CRT, respectively. In multivariate analysis, patients who received primary CRT was at higher risk for tumor recurrence (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.24 to 4.14; p=0.008) and death (OR, 3.02; 95% CI, 1.53 to 5.98; p=0.001) than those who received RH. Grade 3-4, early (17% vs. 30.9%, p=0.021) and late (1.4% vs. 8.8%, p=0.007) complications were significantly less frequent after RH than primary CRT. Conclusion: Thirty percent of patients were cured by RH alone. A treatment outcome was better in this retrospective study in terms of morbidity and survival. Randomized trials are needed to confirm this result [ABSTRACT FROM AUTHOR]

Clinical observation of skin metastasis in ovarian cancer cases is relatively uncommon. And distant metastatic skin lesions including the extremities are much rarer still as most metastatic skin lesions are located in the skin in the abdominal wall adjacent to where the primary ovarian tumors exist. We report the case of a 60-year-old woman who presented skin lesions on both lower extremities as a consequence of the metastasis of serous papillary adenocarcinoma of the ovary. She presented with erythematous and painful cutaneous nodules on both upper legs and in the inguinal area 42 months after initial diagnosis of ovarian cancer. Skin biopsy revealed metastasis of adenocarcinoma in the dermis. She was treated with surgical excision and systemic chemotherapy. Literature review has suggested that a combined modality approach including surgical excision and chemotherapy may be useful in the management of skin metastases due to ovarian cancer. [ABSTRACT FROM AUTHOR]

Thymosinβ10 (Tβ10) regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ10 diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ10, that can overexpress the Tβ10 gene in cancer cells. This was accomplished by replacing the native Tβ10 gene promoter with the human TERT promoter in Ad.TERT.Tβ10. We investigated the cancer suppression activity of Tβ10 and found that Ad.TERT.Tβ10 strikingly induced cancer-specific expression of Tβ10 as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tβ10 decreased mitochondrial membrane potential and increased reactive oxygen species (ROS) production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by Tβ10 overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of Tβ10 by Ad.TERT.Tβ10 could be a valuable anticancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells. [ABSTRACT FROM AUTHOR]

The article evaluates the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC). The researchers found grades 3 and 4 hematologic toxicities such as neutropenia, anemia, and thrombocytopenia. Findings also revealed that hematologic toxicity was the most common side effect of belotecan and carboplatin therapy.

Background: To identify a molecular marker associated with volumetric changes to radiotherapy (RT) in cervical cancer, we compared gene expression profiles of an early response (ER) group with a late response (LR) group, which are defined by complete and partial disappearance of a primary cervical lesion on MRI performed 1 month after completion of RT. Methods: Microarray analysis of mRNA expression profiles was performed in 17 patients (11 in the ER and 6 in the LR group). After selection of the genes with significant differential expression, we evaluated the association of the selected genes with radioresistance in clinical specimens. Results: We identified 53 genes with differential expression on microarray analysis using the permutation test with t statistics (p ≤ 0.01). Using immunohistochemistry, we evaluated the expression of RAR-β, one of the genes selected among the differentially expressed genes. RAR-β expression was significantly down-regulated in the LR group compared with the ER group (p = 0.02). However, this gene did not predict permanent radioresistance (p = 0.19). Conclusions: RAR-β expression might be a valuable marker for the prediction of early volumetric changes to RT in cervical carcinomas. Further search for additional genes associated with early volumetric changes and radioresistance may aid in refining individual treatment strategies. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The objective of the study was to compare the perioperative outcomes, including the operative time, length of hospital stay, and postoperative pain, of a single-port-access laparoscopic-assisted vaginal hysterectomy (SPA-LAVH) and conventional LAVH. Methods: This is a retrospective case–control study. A single surgeon performed 43 SPA-LAVH (cases) between May 2008 and February 2009, and 43 conventional LAVH between September 2005 and April 2008 (controls). Data of the SPA-LAVH cases were collected prospectively into our data registry and we reviewed the data of controls on chart. Results: The demographic parameters, except a history of vaginal delivery, were comparable between the two groups. The SPA group was associated with a history of fewer vaginal deliveries (SPA, 63%; conventional, 84%; p = 0.03). The two groups were comparable with respect to indications for surgery, failed cases from planned procedures, cases requiring additional procedures, and cases needing transfusion. The operative time, estimated blood loss (EBL), drop in hemoglobin preoperatively to postoperative day 1, and postoperative hospital stay were comparable between both groups. SPA-LAVH was associated with reduced postoperative pain. The VAS-based pain scores 24 h (SPA, 2.5 ± 0.7; conventional, 3.5 ± 0.8; p < 0.01) and 36 h after surgery (SPA, 1.7 ± 1.2; conventional, 2.9 ± 1.1; p < 0.01) were lower in the SPA group. There were no complications, including reoperation, adjacent organ damage, and any postoperative morbidity, in both groups. In addition, we have encountered no umbilical complications to date using SPA. Conclusions: Our study demonstrated that SPA-LAVH has comparable operative outcomes to conventional LAVH and the postoperative pain was decreased significantly in the SPA group 24 and 36 h after surgery. [ABSTRACT FROM AUTHOR]

A recent study demonstrated that colorectal cancer (CRC) with ovarian metastases was less responsive to chemotherapy compared with extraovarian metastases. Hence, the ovary may actually represent a “sanctuary” for metastatic cells from CRC. The aim of the study was to investigate the impact of ovarian metastatectomy on survival of CRC patients with ovarian metastasis. Between 1996 and 2008, 83 CRC patients underwent an oophorectomy. For the historical control, 47 CRC patients with ovarian metastasis without resection were included in the analysis. The median age was younger (48 years) in the oophorectomy group compared with the historical control (54 years; P = 0.012). The proportion of synchronous metastasis was higher in the oophorectomy group than in the control group (57 vs. 30%; P = 0.003). After a median follow-up duration of 60.8 months (range of 7.4–169.7 months), the median OS was significantly longer in the oophorectomy group (28.1 vs. 21.2 months, oophorectomy vs. non-oophorectomy; P = 0.038). For ovary-specific survival (date of ovarian metastasis diagnosis to death), CRC patients with an oophorectomy showed a significantly more favorable survival rate than the control group (20.8 vs. 10.9 months; P < 0.001). In univariate analyses, oophorectomy ( P = 0.038), unilaterality of ovarian metastasis ( P = 0.032), metastasis confined to ovaries ( P < 0.001), normal CEA level ( P < 0.001), good performance status ( P = 0.001), palliative chemotherapy ( P = 0.001), and primary disease resection ( P = 0.005) were identified as significantly good prognostic factors for overall survival. The oophorectomy, chemotherapy, metastasis confined to ovaries, normal CEA level, and good performance status retained statistical significance at the multivariate level ( P = 0.003, P = 0.004, P = 0.005, P = 0.015, and P = 0.029, respectively). Based on this retrospective analysis, the ovarian metastatectomy significantly prolonged survival in CRC patients with ovarian metastases. The potential role of an ovarian metastatectomy in the management of CRC should be prospectively studied. [ABSTRACT FROM AUTHOR]

Aim: To better predict treatment responses for managing bulky cervical carcinoma with neoadjuvant chemotherapy (NAC). Methods: The expression of p-STAT3 was analyzed by immunohistochemistry using paraffin-embedded pretreatment cervical biopsy tissues. The study included 29 patients with bulky IB to IIA cervical squamous cell carcinoma treated with NAC. Results: Twenty (69.0%) of 29 patients were scored as p-STAT3-positive. Pathological response to chemotherapy (complete response or residual tumor with less than 3 mm stromal invasion) was observed in eight patients (27.6%). The p-STAT3-positive patients had a longer disease-free survival compared to p-STAT3-negative patients ( P = 0.03), though they had more frequent clinical nodal involvement ( P = 0.046). Conclusion: Pretreatment assessment of p-STAT3 expression may provide additional information for the identification of patients with cervical cancer who have a favorable prognosis. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to evaluate the psychometric properties of the Korean version of the Quality of Life questionnaire cervical cancer module (QLQ-CX24), developed by the European Organization for Research and Treatment of Cancer (EORTC). Methods: The EORTC QLQ-CX24 and the core questionnaire (the EORTC QLQ-C30) were administered to 860 Korean disease-free survivors of cervical cancer and 494 female control subjects from the general Korean population. The construct reliability and validity of the EORTC QLQ-CX24 questionnaire were assessed via factor analysis, multitrait scaling analyses and known group comparisons. Results: Factor structure of the Korean version of the EORTC QLQ-CX24 questionnaire agreed with the originally hypothesized scale structure. Scale reliability was confirmed by Cronbach’s α coefficients for internal consistency, which ranged from 0.78 to 0.87. Convergent and discriminant validity was confirmed by multitrait scaling analysis, which revealed scaling errors of 0.9. The clinical validity of the Korean version of the EORTC QLQ-CX24 was demonstrated by the ability to discriminate among controls and patient subgroups of different stages, treatments and overall health status. Conclusions: The Korean version of the EORTC QLQ-CX24 was found to be a reliable and a valid measure of quality of life among survivors of cervical cancer when administered in a large survey setting. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Galectin-3 is expressed widely in epithelial and immune cells and the level of expression varies in many cancer cells relative to the normal tissues from which they arise. We investigated whether the expression of galectin-3 is associated with the progression of cervical neoplasia. Methods: Galectin-3 expression was evaluated in fresh frozen tissues of cervical carcinoma using real-time quantitative RT-PCR. In addition, galectin-3 expression was evaluated at the protein level by immunohistochemistry in 90 formalin-fixed paraffin-embedded cervical tissues, 10 normal cervical specimens, 20 low-grade squamous intraepithelial lesions (LSILs), 20 high-grade squamous intraepithelial lesions (HSILs), and 40 invasive squamous cell carcinomas (ISCCs). Results: Real-time quantitative RT-PCR revealed that galectin-3 expressions in tumor cells were significantly downregulated compared with corresponding normal tissue ( P=0.005). Moreover, immunohistochemistry showed that galectin-3 expression was strong in all normal cervical squamous epithelia and gradually decreased in accordance with the histopathologic grades in order LSIL > HSIL > ISCC ( P<0.001). Conclusions: These data constitute the first observation that the expression of galectin-3 is downregulated in cervical cancer tissues and suggest that the decreased expression of this galactoside-binding lectin is associated with the progression of cervical neoplasia. [ABSTRACT FROM AUTHOR]

Aim: This study was performed to evaluate the efficacy of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who were inadequate for primary optimal surgery. Methods: Patients with histologically confirmed epithelial ovarian cancer at International Federation of Gynecology and Obstetrics stages IIIc/IV that was unresectable according to computed tomography findings were eligible for this study. Three cycles of paclitaxel plus cisplatin NAC were administered and the response was evaluated. Patients were then selected for interval debulking surgery or three cycles of additional chemotherapy with the same regimen according to the resectability and response. Interval debulking surgery followed by second-line chemotherapy was applied to patients with no response to NAC. During the same period, patients who did not agree to the protocol were treated by the conventional method of tumor debulking surgery followed by adjuvant chemotherapy, and served as the control group. A comparison of both groups of patients was carried out. Results: A total of 40 patients were involved in the study. All patients were evaluable. Eighteen patients underwent NAC and 22 patients were treated by conventional therapy. Optimal debulking was possible in 14 patients (77.8%) in the NAC group and in 10 patients (45.5%) in the conventional therapy group ( P = 0.04). The mean estimated blood loss was 620 cc (range: 300–1500 cc) in the NAC group and 1061 cc (range: 300–3500 cc) in the conventional therapy group ( P = 0.04). However, no significant differences were found in the disease-free and overall survival rates between the two groups ( P = 0.48 and P = 0.61, respectively). Conclusion: NAC provided a higher rate of optimum cytoreduction and equivalent survival with less invasive surgery and reduced morbidity compared with conventional therapy in patients with advanced epithelial ovarian cancer inadequate for primary optimum surgery. Therefore, NAC may be a valuable alternative treatment for these patients. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objective: Indocyanine green with near-infrared fluorescence imaging (NIR-ICG) is a new tracer modality in the limelight used for lymphatic mapping. The advantage of this method is to provide real-time image during surgery. To use ICG for image guided lymph node dissection, a surgeon needs to know initial appearing time and duration. Methods: A 52-year-old woman undertook surgery diagnosed with endometrial cancer. She had no past medical history and her body mass index was 25.3 kg/m2. Preoperative magnetic resonance imaging examination revealed 2.7 cm sized cancerous mass in the endometrial cavity with superficial myometrial invasion without lymph node enlargement. Four mL (1.25 mg/mL) of ICG solution was prepared for injection. For each site, 1 mL of solution was injected superficially, 2-3 mm into the cervical submucosa and another 1 mL was injected deep, 1-2 cm into the stroma of the cervix [1,2]. We recorded video with 30° 10 mm scope equipped with a specific lens and light source emitting both visible and NIR light (KARL STORZ GmbH & Co. KG, Tuttlingen, Germany). Results: Pelvic lymph node was visualized from around 5 minutes. ICG was dispersed into organs after hysterectomy (53 minutes after ICG injection), yet we could clearly identify sentinel lymph node (SLN). Pathology revealed endometriod adenocarcinoma grade I, myometrial invasion with less than half of myometrium and no lymph node metastasis. Conclusion: Cervical injection of ICG provides good visualization of SLN from 5 minutes to over an hour. Our film gives an idea about time management to make a plan for surgery and not to miss SNLs. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment of BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer remains unknown. Recently, there is an increase in the evidence to support the role of the combination of a poly(adenosine diphosphate-ribose) polymerase inhibitor, anti-angiogenic agents, and immunotherapy as maintenance therapy in BRCA wild-type patients with platinum-sensitive recurrence. We hypothesized that adding pembrolizumab and bevacizumab to olaparib maintenance can increase progression-free survival (PFS) in BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer. Methods: BRCA wild-type patients who received two previous courses of platinum-containing therapy, achieved complete or partial response to last treatment, and the treatment-free interval is >6 months after the penultimate platinum-based chemotherapy offered olaparib maintenance with pembrolizumab and bevacizumab. Forty-four patients will be included from 4 sites across Singapore and Korea. The primary endpoint of the study is 6-month PFS rate. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine possible prognostic factors in patients with uterine leiomyosarcoma (LMS). Methods This study retrospectively investigated 48 patients with uterine LMS treated in Samsung Medical Center between 2008 and 2017. To analyze the prognostic significance of factors for recurrence-free survival (RFS), overall survival (OS), and survival after recurrence, the log-rank test and Cox proportional hazards model were used for univariate and multivariate analysis. Results Of the 48 patients, twenty-nine patients (60.4%) experienced recurrence and 16 patients (33.3%) died within a median follow-up period of 20 months (range, 3-99months). On multivariate analysis, older age, presence of residual tumor after surgery, lower mitotic count, and history of adjuvant radiotherapy at first treatment were significantly associated with better RFS. Presence of residual tumor after surgery and severe nuclear atypia were associated with poor OS. In analysis of survival after recurrence, hematogenous recurrence, severe nuclear atypia, and presence of residual tumor at primary surgery were significantly associated with worse prognosis. Notably, residual tumor status at primary surgery was associated with RFS, OS, and survival after recurrence. Conclusions We demonstrated possible prognostic factors for RFS, OS, and survival after recurrence for patients with LMS. These results may provide useful information for patients with LMS. [ABSTRACT FROM AUTHOR]

Abstract In this multicenter, open-label, single-arm, Phase II study with Simon two-stage optimum design (NCT04361370), we investigate the efficacy and safety of triplet maintenance (olaparib, pembrolizumab, bevacizumab) in patients with platinum-sensitive recurrent ovarian cancer who are wild-type for BRCA 1/2. A total of 44 patients were enrolled, and the median follow-up duration was 22.9 months (interquartile range: 17.4–24.7). The primary outcome was 6-months progression-free survival (PFS), which was 88.6% (95% confidence interval [CI] 75.4–96.2), meeting the pre-specified primary endpoint. The secondary outcomes reported here include median PFS, 12-months PFS, and overall survival and safety. The median PFS was 22.4 months (20.4–∞), with a 12-months PFS rate of 84.0% (95% CI 69.3–92.0). The median overall survival was 28.6 months (27.3–∞). The combination demonstrated tolerable toxicity with manageable side effects. Other secondary outcomes include time-to-progression, time to subsequent treatment, time to second treatment and PFS2; however, this data is not reported, as treatment is still ongoing in a majority of patients. Exploratory analysis shows that patients who were homologous recombination deficiency-positive or had a programmed death-ligand 1 combined positive score ≥1 showed a favorable response (P = 0.043 and P

A response by Byoung-Gie Kim to a letter to the editor about his article on synchronous cancers of endometrium and ovary in the December 2011 issue is presented.

Objective: The aim of NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARP inhibitor (PARPi). Methods: This study includes patients with platinum-sensitive recurrent ovarian cancer who had received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Patients who had responded to the last platinum regimen are eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression. The primary endpoint of the study is 6-month progression-free survival (PFS) rate. A Simon 2-stage design was utilized. Target accrual was 22 patients in the first stage; =13 patients without progressive disease within 6 months was required to proceed to second stage. Results: We report the results from the first stage. Median age was 56 years old, high grade serous and most of the patients (90.9%) had high-grade serous carcinoma. Of the 22 patients from the first stage, 9 had progressive disease within 6 months (6-month PFS rate=66.5%; 95% confidence interval=48.9%-90.2%). The efficacy boundary to proceed to the second stage was met. No grade 4 treatment-related adverse events were reported, and no TRAEs leading to treatment discontinuation. Conclusion: Our findings indicate encouraging safety and activity of niraparib + bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi in the future. [ABSTRACT FROM AUTHOR]

Objective: The standard treatment for advanced endometrial cancer (EC) includes platinum-based combination chemotherapy (CT), regardless of the histology, molecular status and the patient's profile. However, EC patients are a particularly frail group of patients, often with co-morbidities. Tolerance of CT can be difficult and induce long-term toxicities. In advanced EC disease, anti-PD1 immunotherapy has shown impressive results amongst mismatch repair deficient (MMRd)/high microsatellite instability (MSI-H) tumors. However, the benefit of adding CT to anti-PD1 is still an opened question. The aim of DOMENICA is to address the question if PD-1 alone has superior efficacy to CT, so that therapy in 1L advanced/recurrent MMRd/MSI-H EC could be de-escalated to avoid CT related toxicities. Methods: DOMENICA is an academic international randomized open-label, phase III trial evaluating the efficacy and safety of dostarlimab versus carboplatin-paclitaxel in patients with MMR deficient (MMRd/MSI-H) relapse or advanced / metastatic EC. Inclusion criteria for the study comprised patients with histologically confirmed EC exhibiting recurrent or advanced disease, including primary stage IIIA to C2 or Stage IV disease, or experiencing their first recurrence of EC without curative treatment, provided they had evaluable disease according to RECIST 1.1 criteria. Additionally, patients with MMRd/MSI-H tumors, determined by institutional MMR immunohistochemistry testing, and those with a performance status (ECOG) of 0-1 were eligible. The primary endpoint is progression-free survival according to RECIST 1.1, assessed by the BICR (Blinded Independent Central Review). Secondary endpoints include overall survival as key secondary endpoint, progression-free survival 2, patients reported outcome, best objective response rate, disease control rate, duration of response rate, safety and tolerability, time to first or second subsequent treatment (TFST, TSST), pharmacokinetics and immunogenicity of dostarlimab. Exploratory objectives include predictive biomarkers, efficacy according to geriatric status. The Study is ongoing in France (GINECO), Spain (GEICO), Italy (MaNGO, MITO), Canada (PMC), Singapore (GCIG), South Korea (KGOG), Japan (GOTIC), Turkey (TRSGO), and UK (NRCI). [ABSTRACT FROM AUTHOR]

Objective: The real-world INFORM study analyzed sociodemographics, treatment patterns and clinical outcomes for patients with newly diagnosed advanced epithelial ovarian cancer (EOC) in Australia, South Korea (S.Korea) and Taiwan preceding incorporation of poly(ADPribose) polymerase inhibitors into clinical practice. Methods: Retrospective data from patients diagnosed with EOC (high-grade serous EOC for Taiwan) between January 2014 and December 2018 with =12 months follow-up from diagnosis were analyzed descriptively. Survival was evaluated by Kaplan-Meier with two-sided 95% confidence interval (CI). Results: Of the 987 patients (Australia, 223; S.Korea, 513; Taiwan, 251), 98% received platinum-based chemotherapy (CT). In S.Korea and Taiwan 76.0% and 78.9% respectively underwent primary cytoreductive surgery; in Australia, 56.5% had interval debulking surgery. Bevacizumab was included in primary/maintenance therapy for 22.4%, 14.6% and 6.8% of patients in Australia, S.Korea and Taiwan, respectively. Patients receiving bevacizumab were high-risk (reimbursement policy) and achieved similar real-world progression-free survival (PFS) compared with CT only. Overall, the median real-world PFS (months; 95% CI) was similar across Australia (16.0 [14.63-18.08]), S.Korea (17.7 [16.18-19.27]) and Taiwan (19.1 [17.56-22.29]). Conclusion: This study reveals poor prognosis despite differences in demographics and treatment patterns for patients with EOC across Asia-Pacific suggesting the need for biomarker-driven novel therapies to improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: The recently updated World Health Organization classification divides endocervical adenocarcinomas (ADCs) into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) ADCs. This study aimed to investigate the differences in the clinical features and treatment outcomes between patients with HPVA and HPVI. Methods: We retrospectively reviewed the electronic medical records and pathology slides of 123 patients with endocervical ADC who underwent radical hysterectomy and adjuvant radiation therapy. Tumor characteristics, patterns of failure, and survival outcomes were compared between HPVA and HPVI ADCs. Results: Eighty-one (65.9%) and 42 (34.1%) patients were diagnosed with HPVA and HPVI ADCs, respectively. HPVI ADC showed more frequent positive vaginal resection margin (VRM) and peritoneal seeding than HPVA ADC. After a median follow-up of 58.1 months, local recurrence and distant metastasis were more frequently observed in HPVI ADC than in HPVA ADC. Both local recurrence-free survival (77.3% vs. 91.8%) and distant metastasis-free survival (50.1% vs. 73.7%) rates of HPVI ADC were lower than those of HPVA ADC. Diseasefree survival was not significantly different between HPVI and HPVA ADCs. Conclusion: We demonstrated that HPVI ADC exhibited higher rates of VRM involvement and peritoneal seeding than those of HPVA ADC, resulting in higher rates of local recurrence and distant metastasis. Further studies with larger populations are warranted to explore optimal treatment strategies based on the histological subtypes of endocervical ADC. [ABSTRACT FROM AUTHOR]

Background: Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi. Methods: The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate. Accrual is expected to be completed in 2022, followed by presentation of results in 2023. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to evaluate the effect of waiting time, from diagnosis to initiation of definitive concurrent chemoradiation (CCRT), on overall survival in cervical cancer patients. Materials and Methods Patients with cervical cancer who were treated with definitive CCRT between 2000 and 2017 were retrospectively reviewed. Time from initial pathological diagnosis to definitive CCRT was analyzed both as a continuous variable (per day) and as a categorical variable in two groups (group 1 = median, group 2 > median). Patients with a waiting time of more than 60 days were excluded. Results The median waiting time was 14 days (0-60). There were differences between group 1 and group 2 in age and chemotherapy regimens. However, no significant difference was found in the International Federation of Gynecology and Obstetrics stage, cell type, or the number of cycles of chemotherapy received during CCRT. A longer waiting time was associated with poorer overall survival on the Kaplan-Meier curve (group 1 vs. group 2, p=0.042). On multivariate analysis, intervals as either a continuous variable (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006 to 1.040; p=0.007) or a categorical variable (HR, 1.513; 95% CI, 1.073 to 2.134; p=0.018), FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT were significant independent prognostic factors for overall survival. Conclusion A shorter waiting time from pathological diagnosis to definitive CCRT showed benefit on overall survival. Our findings suggest that an effort to minimize waiting times should be recommended in cervical cancer patients who are candidates for CCRT. [ABSTRACT FROM AUTHOR]

Recently, a procedure for detecting ROS-sensitive proteins that contain active cysteine residues was developed. The method is based on the fact that biotin-conjugated iodoacetamide (BLAM) and ROS competitively and selectively react with the active cysteine residues in ROS-sensitive proteins. To investigate the role of ROS in cervical cancer, BIAM labeling on cytosolic proteins in normal and cancer tissues was performed, respectively. The BIAM labeling proteins are separated by 2-dimensional electrophoresis, and then identified by MALDI-TOF mass analysis. ROS-sensitive protein is identified as creatine kinase B containing cysteine residue in active center. Activity of creatine kinase B in normal tissue is higher than that of oxidized form In cervical cancer tissues. The result suggests that ROS play an important role in metabolic regulation in cervical cancer cells. However, molecular mechanisms that ROS and creatine kinase B are integrated into a physiological signal leading to the cellular transformation remain to he elucidated. [ABSTRACT FROM AUTHOR]

Objective: Unlike cervical squamous cell carcinoma, there are no consensus criteria for serum tumor markers in cervical adenocarcinoma. This study aimed to identify the prognostic value of preoperative carbohydrate antigen 125 (CA125) levels in cervical adenocarcinoma patients with adverse pathologic features. Methods: A total of 105 patients who underwent radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiation therapy were included. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Cox proportional hazard regression model. Results: Using a cutoff value of 50 U/mL, 83 and 22 patients had low- and high-CA125, respectively. Patients with high-CA125 had a larger tumor size, more frequent parametrial extension, and more frequent lymph node metastasis than those with low-CA125. During a median follow-up of 59.3 (interquartile range, 32.7-97.8) months, patients with high-CA125 showed inferior 5-year LRFS, DMFS, and OS rates compared to those with low-CA125 (38.5% vs. 70.0%; 37.0% vs. 69.4%; 43.6% vs. 78.1%, respectively, all p<0.05). In multivariable analysis, the high-CA125 remained significant prognostic factor for LRFS, DMFS, and OS (all p<0.05). Furthermore, 12 patients with high-CA125 at recurrence exhibited lower 5-year OS rates than 21 patients with low-CA125 at recurrence (0.0% vs. 51.3%, p=0.003). Conclusion: In this retrospective analysis, the serum CA125 level at diagnosis and recurrence was related to the extent of disease and prognosis of cervical adenocarcinoma with adverse pathologic features. A CA125 level of =50 U/mL may be a prognostic surrogate marker for cervical adenocarcinoma in patients with the presence of adverse factors. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer. Materials and Methods We identified 116 patients treated with definitive RT, including FDG-PET/CT-guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed. Results We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax < 50% (n=29) (DFS, 76% vs. 35%, p < 0.001; OS, 90% vs. 41%, p < 0.001, respectively). Adenocarcinoma was frequently observed in ΔSUVmax < 50% compared to ΔSUVmax ≥ 50% (27.6% vs. 10.3%, p=0.003). In addition, models incorporating metabolic parameters showed improved accuracy for predicting DFS (p=0.012) and OS (p=0.004) than models with clinicopathologic factors. Conclusion Changes in metabolic parameters, especially those in SUVmax by > 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT. [ABSTRACT FROM AUTHOR]

Abstract Although the concurrent use of a chemotherapeutic agent and radiotherapy improves survival in patients with locally advanced or recurrent cervical cancer, severe side effects related to chemotherapy are frequent and may result in a low quality of life for the patients. In this study, we investigated the effects of a combination of Wee1 inhibitor (AZD1775) and irradiation in cervical cancer. In vitro effects of AZD1775 with irradiation in human cervical cancer cells were assessed by clonogenic survival and apoptosis assays. The effects on DNA damage response signaling and the cell cycle were also explored. Tumor growth delay was evaluated to investigate the in vivo effects of AZD1775 with irradiation in cervical cancer mouse models, including xenografts and patient-derived xenografts (PDXs). The co-treatment of AZD1775 and irradiation significantly decreased clonogenic survival and increased apoptosis in cervical cancer cells. These effects were associated with G2 checkpoint abrogation which resulted in persistent DNA damage. Both in the xenografts and the PDXs, the co-treatment significantly decreased tumor growth compared tothe irradiation alone (p

Purpose Lymph node metastasis (LNM) is the most significant prognostic factor in cervical cancer that was recently incorporated into the International Federation of Gynecology and Obstetrics (FIGO) staging system. This study was performed to evaluate whether the prognostic significance of LNM differs according to disease status. Materials and Methods Patients with FIGO stage IB or higher cervical cancer who had pretreatment computed tomography and/or magnetic resonance imaging studies as well as long-term follow-up were enrolled in this retrospective study. The hazard ratio (HR) of Cox regression was used to determine the prognostic significance of LNM. The HRs were compared between the different tumor groups (based on stage, histology, tumor size, primary treatment, age, parametrium involvement, and lymphovascular space invasion). Results A total of 970 patients treated between January 1999 and December 2007 were included. The pretreatment LNM had prognostic significance in patients with stage IB1/IIA (HR for progression-free survival 2.10, p=0.001; HR for overall survival 1.99, p=0.005). However, the significance gradually decreased or disappeared with advancing stages. Similarly, the prognostic significance of the pretreatment LNM decreased with advancing disease status, including old age, parametrial involvement or lymphovascular space involvement. In contrast, the tumor size was associated with the prognostic significance of LNM with advancing status. The significance of the clinical LNM did not reflect the significance of the clinical stage. In contrast, the tumor size, parametrial involvement, and significance of the pathologic LNM reflected the clinical stage. Conclusion In patients with cervical cancer, pretreatment LNM on imaging has different clinical significance depending on the tumor status. [ABSTRACT FROM AUTHOR]

Background: Secondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation.Methods: We randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel-carboplatin or gemcitabine-carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival.Results: A total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P = 0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery.Conclusions: In this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.). [ABSTRACT FROM AUTHOR]

Objective To demonstrate the survival impact of intraoperative tumor rupture in women with stage I clear cell carcinoma (CCC) of the ovary. Methods A total of 193 patients with stage I CCC of the ovary who had undergone a complete staging operation followed by ≥ three cycles of adjuvant platinum-based chemotherapy, were retrospectively reviewed. Survival analysis was performed and compared between three stage groups: IA/IB, IC1, and IC2/IC3. Results There were 70, 51, and 72 women with ovarian CCC in stages IA/IB, IC1, and IC2/IC3, respectively. Intraoperative tumor rupture occurred in 69 (35.8%) patients. Gross endometriosis (p = 0.020) and significant peritumoral adhesion (p < 0.001) were associated with intraoperative tumor rupture. However, neither laparoscopic approach nor large tumor size > 10 cm were associated with intraoperative tumor rupture. Patients with stage IC2/IC3 compared to those with stage IC1, had poorer progression-free survival (PFS) (5-year PFS, 68.5% versus 91.7%; p = 0.010) and overall survival (OS) (5-year OS, 81.1% versus 95.4%; p = 0.027). However, there was no significant difference between patients with stages IA/IB and IC1 CCC in PFS (5-year PFS 88.8% versus 91.7%; p = 0.291) and OS (5-year OS 94.6% versus 95.4%; p = 0.444). Stage IC2/IC3 was the only independent poor prognostic factor for OS (hazard ratio, 3.50; 95% confidence interval, 1.31 to 9.36). Conclusion Surgical spillage of tumor cells does not appear to have a negative impact on survival outcomes of women with stage I ovarian CCC who received ≥ three cycles of adjuvant platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Objective The renin-angiotensin system (RAS) influences cardiovascular homeostasis, and Angiotensin II type 1 receptor (AGTR1) is the main effector of RAS, and AGTR2 antagonizes AGTR1. Accumulating evidence supports the role of RAS in the paracrine regulation of tumorigenesis in several cancer types. Although treatment with AGTR1 antagonist (losartan) or AGTR2 agonist (CGP42112A) inhibits tumor progression in several cancer cells, their combined treatment has not been reported. Methods In this study, we estimated the expression of AGTR1 and AGTR2 in epithelial ovarian cancer cells and tissues. Then, we evaluated the anti-cancer effects of combined treatment with losartan and/or CGP42112A in ovarian cancer cells and human umbilical vein endothelial cells (HUVEC). Results AGTR1 protein was detected in 86% of ovarian cancer tissues, while AGTR2 was not detected in immunohistochemistry. The mRNA expression of AGTR1 obtained from the cancer genome atlas (TCGA) dataset showed that AGTR1 overexpression was correlated with poor survival. Treatment with either losartan or CGP42112A reduced the angiotensin II (Ang II)-mediated cell survival in both ovarian cancer cells and HUVEC. Combined treatment with losartan and CGP42112A synergistically decreased cell survival. As a downstream pathway, phosphorylation of phospholipase C β3 (PLC β3) and expression of vascular endothelial growth factor (VEGF) decreased synergistically in combined treatment. Conclusion The results suggest that dual regulation of AGTR1 and AGTR2 may be a novel therapeutic strategy for epithelial ovarian carcinoma through inhibition of cancer cell survival as well as anti-angiogenesis. Translational relevance This study investigated the expressions of AGTR1 and AGTR2 in epithelial ovarian carcinoma and the therapeutic potential of AGTR modulation with specific antagonist and/or agonist in epithelial ovarian cancer cells. Treatment of AGTR1 antagonist, losartan and/or AGTR2 agonist, CGP42112A synergistically mediated anti-cancer effects including the decrease of cell survival and down-regulation of VEGF. [ABSTRACT FROM AUTHOR]

Purpose A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m² was administered once weekly for 5 weeks during radiation therapy. Results Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study. [ABSTRACT FROM AUTHOR]

Purpose: Clear cell carcinoma (CCC) is a rare histologic subtype that demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology Group conducted the first randomized phase III, CCC-specific clinical trial that compared irinotecan and cisplatin (CPT-P) with paclitaxel plus carboplatin (TC) in patients with CCC., Patients and Methods: Six hundred sixty-seven patients with stage I to IV CCC of the ovary were randomly assigned to receive irinotecan 60 mg/m(2) on days 1, 8, and 15 plus cisplatin 60 mg/m(2) on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m(2) plus carboplatin area under the curve 6.0 mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression-free survival. Secondary end points were overall survival, overall response rate, and adverse events., Results: Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC., Conclusion: No significant survival benefit was found for CPT-P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC., (© 2016 by American Society of Clinical Oncology.)

Purpose: Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy., Patients and Methods: Nine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators., Results: Maintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%)., Conclusion: Pazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697)., (© 2014 by American Society of Clinical Oncology.)