Recurrent Endometrial Carcinoma Research Articles

Medical therapy for recurrent endometrial carcinoma following conventional platinum based cytotoxic chemotherapy

Medical therapy for recurrent endometrial carcinoma following conventional platinum based cytotoxic chemotherapy

A phase II trial of durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma.

5582 Background: Monoclonal antibodies Durvalumab (D) and Tremelimumab (T) inhibit binding of programmed cell death ligand 1 (PDL1) to PD1 and inhibit activation of cytotoxic T-lymphocyte-associated protein 4 (CTLA4), respectively, resulting in improved tumor immunosurveillance. There is rationale to study D and DT based on recent genomic and tumor microenvironment evaluation of endometrial cancer (EC). Methods: Eligible patients (pts) were randomized to D or DT. Pts received D 1500 mg intravenously (IV) every 4 weeks (wks). DT therapy pts received D 1500 mg IV every 4 wks and T 75 mg IV every 4 wks for 4 cycles, followed by D 1500 mg IV every 4 wks until progression or unacceptable toxicities. Pts were stratified by histology with 10 carcinosarcoma or MSI-H EC pts per arm. Efficacy assessments were every 8 wks and treatment related adverse events (TRAEs) were assessed per CTCAE v.4.03. The primary endpoint was overall response rate (ORR) by RECIST v1.1. Descriptive statistics and 90% one sided CI are reported. Progression free survival (PFS) rate at 24 wks (PFS24wks) was estimated by Kaplan Meier method. Results: At planned interim analysis, 56 pts were enrolled (28 per arm). 15 pts: carcinosarcoma, 15 pts: endometrioid (3: Gr1), 14 pts: serous, and 12 pts: other histology. 5(9%) pts: MSI-H, 48(86%) pts: microsatellite stable (MSS), 3(5%): unknown. 2 pts were excluded due to early death. 27 pts per arm were evaluable for efficacy. In the D arm: 1 pt had complete response (CR)(MSS) and 3 pts had a partial response (PR) (2:MSS, 1:MSI-H) with an ORR of 14.8% (CI: 6.6-100%). The median PFS was 7.6 wks and PFS24wks was 13.3% (CI 6.1-100%). Median duration of response (DOR) was 16 wks in the D arm. In the DT arm, 2 pts achieved CR (1:MSI-H, 1:MSS) and 1 had PR (MSS). The ORR was 11.1% (CI: 4.2-100%). Median PFS was 8.1 wks, PFS24wks was 18.5% (CI 10.1-100%) and DOR was 8 wks. Grade 3 TRAEs occurred in 2 (7%) pts in D and 9 (32%) pts in DT. Grade 4 TRAEs occurred 1 (4%) pt in D and 3 (11%) pts in DT. 2 pts discontinued due to a TRAE. Most common TRAEs in total were fatigue (23%), diarrhea (20%), nausea (14%), vomiting (13%) and pruritis (11%). Conclusions: D and DT show modest activity in EC. No new safety signals were identified. Second stage accrual is ongoing. Clinical trial information: NCT03015129.

The antitumor effect of lobaplatin against Ishikawa endometrial cancer cells in vitro and in vivo

The new effective chemotherapeutic drugs are required urgently for advanced and recurrent endometrial carcinoma (EC), which is one of the most common gynaecological tumors among women worldwide. Preclinical studies have shown that lobaplatin, one of the third-generation platinum compounds, has possessed powerful anti-cancer efficacy on a series of tumors. The purpose of this study is to investigate its effect and molecular mechanism on the growth of endometrial cancer cell line Ishikawa in vitro and in vivo. The results of cell counting kit-8 (CCK-8) shown that lobaplatin concentration-dependent inhibited cell proliferations in human endometrial carcinoma ishikawa cells. Flow cytometry (FCM) assay demonstrated that lobaplatin affected the survival of endometrial carcinoma cell by arresting cell cycle at S phase and G2/M phase and inducing apoptosis in dose-dependent manner. Moreover, Western blot analysis also showed that the apoptosis-inducing effects of lobaplatin was associated with the reduction of Bcl-2 expression while upregulation of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9 and Bax. Meanwhile, lobaplatin significantly suppressed tumor growth of human Ishikawa xenograft models and terminal deoxynucleotidyl trans-ferase dUTP nick end labeling confirmed the significant occurrence of lobaplatin-treated tumor tissues of apoptosis. Therefore, lobaplatin could be an effective chemotherapeutic agent for human endometrial carcinoma and warrants further clinical investigation.

Recurrent early stage endometrial carcinoma presenting as vaginal and colonic metastasis: A rare case report

Recurrent early stage endometrial carcinoma presenting as vaginal and colonic metastasis: A rare case report - IJOGR- Print ISSN No: - 2394-2746 Online ISSN No:- 2394-2754 Article DOI No:- 10.18231/2394-2754.2019.0027, Indian Journal of Obstetrics and Gynecology Research-Indian J Obstet Gynecol Res

Platinum rechallenge in second-line treatment for endometrial carcinoma

Objectives: Metastatic endometrial carcinoma (EC) has a poor prognosis. Systemic treatment (hormone therapy or chemotherapy) has been used in first line, however, the best therapy as second-line therapy is not known. The aim of this study is to evaluate the role of platinum-based chemotherapy rechallenge in second-line treatment for EC. Materials and Methods: Retrospective review of patients with recurrent EC who were treated with second-line systemic therapy from April 2007 to April 2015 at two cancer centers. Clinical data included: age, histology, tumor grade, tumor stage at diagnosis, site of disease progression, ECOG performance status, adjuvant chemotherapy, first-and second-line chemotherapy for recurrent disease and comorbidities. Results: A total of 84 patients were evaluated. Median age was 66.2 years; most patients had endometrioid histology (67.9%) and grade 2 tumors (45.8%). Twenty-nine patients (34.5%) were treated with platinum rechallenge at second line. Median overall survival (OS) was 9.7 months (7.1-12.3 months; 95% CI). Longer OS was observed in platinum rechallenge group compared to non-re-exposed (13.8 months vs. 7.9 months, p = 0.005). Only platinum rechallenge was significantly associated to a better OS on multivariate analysis (HR 0.43 [95%CI 0.21-0.87, p = 0.019]). Platinum rechallenge was also associated with a higher progression-free survival (PFS) (4.9 months vs. 3.4 months, p = 0.008). Conclusions: The present findings suggest a longer OS and PFS for patients treated with platinum rechallenge at second-line treatment for EC and add more evidence for adoption of this strategy in a scenario where there is little evidence of effective treatments.

Clinical and prognostic value of 18F-FDG PET/CT in recurrent endometrial carcinoma

PurposeEndometrial carcinoma (EC) is a cancer with a good overall prognosis, except in cases of recurrent or advanced EC. The aim of this study was to assess the diagnostic performance, the prognostic value and the impact on therapeutic management of 18F-FDG-PET/CT in suspected recurrent EC. Materials and methodsWe retrospectively evaluated 157 patients with histologically proven EC and restaging 18F-FDG-PET/CT for suspected recurrence. The PET images were analyzed visually and semi-quantitatively by measuring SUVmax, MTV and TLG. A combination of clinical/imaging follow-up and/or histopathology was taken as reference standard. PFS and OS were computed using Kaplan–Meier curves. ResultsSeventy-nine patients had positive 18F-FDG-PET/CT showing the presence of at least one hypermetabolic lesion consistent with recurrence, while the remaining 78 were negative. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG-PET/CT were 96%, 99%, 99%, 96%, 97% respectively and were higher compared to conventional imaging: 97%, 62%, 72%, 96%, 80%. After a mean follow-up of 39 months, relapse/progression occurred in 58 patients and death in 37 with an average time of 22.1 and 27.6 months respectively. A positive 18F-FDG-PET/CT and advanced FIGO stage were significantly associated with shorter PFS and OS. PET/CT results had a significant impact on therapeutic approach in 33 patients: avoiding unnecessary therapies in 28 and modifying therapy in 5. Conclusions18F-FDG-PET/CT has a very good diagnostic performance in patients with suspected recurrent EC and has an important prognostic value in assessing PFS and OS. Moreover, PET/CT allowed for a change in treatment decision in about 20% of cases.

690 - Laparoscopic Selective Resection of Isolated Pre-Caval and Pre-Aortic Nodal Recurrence in Endometrial Carcinoma

690 - Laparoscopic Selective Resection of Isolated Pre-Caval and Pre-Aortic Nodal Recurrence in Endometrial Carcinoma

GOG 3007, a randomized phase II (RP2) trial of everolimus and letrozole (EL) or hormonal therapy (medroxyprogesterone acetate/tamoxifen, PT) in women with advanced, persistent or recurrent endometrial carcinoma (EC): A GOG Foundation study

Objective: Preclinical and clinical evidence has documented that blockade of the PI3K/AKT/mTOR pathway may suppress and/or overcome resistance to endocrine therapy in several solid tumors, including endometrial carcinoma (EC). The efficacy of everolimus and letrozole (EL) in women with recurrent EC has been reported. This trial was designed to determine the response, adverse events (AEs), and progression free survival (PFS) of EL or medroxyprogesterone acetate/tamoxifen (PT) in the treatment of metastatic EC.

Detection of the DICER1 hotspot mutation alongside immunohistochemical analysis may provide a better diagnostic measure for ovarian Sertoli-Leydig cell tumors

BackgroundTo evaluate the clinicopathological and histopathological characteristics of ovarian Sertoli-Leydig cell tumors (SLCTs) in relation to differential diagnosis, and patient prognosis. MethodsA review of clinical data, pathological morphology and immunohistochemical analysis of SLCTs were performed in 18 SLCTs patients. The DICER1 gene mutation was assessed in eight cases that were obtained from in-house surgical resections. ResultsAmong 18 SLCTs patients, three cases had well-differentiated tumors, 8 cases had moderately-differentiated tumors, and the remaining 7 cases had poorly-differentiated tumors. Among the moderately-differentiated tumors, three cases occurred coincidently with other diseases – one case occurred with endometrial carcinoma (grade I), and two cases with endometrial carcinoma of the ovary (grade 2 and grade 3). Immunohistochemical staining for α-inhibin, calretinin, and FOXL2 was positive in all the biopsies tested. The intensity of staining varied depending on the percentage of Sertoli cells and the primitive gonad interstitial composition. DICER1 mutations were detected in three of eight cases that were evaluated and were significantly more in low age range patients (P < 0.05). The initial symptoms of these three cases were sexual changes and elevation of androgen levels. The follow-up time in this study ranged from 3 to 87 months with the mean follow-up time of 29.1 months. Prognosis was generally favorable. There was no recurrence or metastasis in any patient, except for one case with recurrence of endometrial carcinoma. ConclusionThe clinical presentation of SLCTs can be both varied and complex. Pathological examination is imperative for both diagnostic and prognostic grading. Immunohistochemical stain of α-inhibin, FOXL2, and calretinin and genetic testing for DICER1 mutations will be more potent for differential diagnosis.

Nimotuzumab in the Management of Recurrent Endometrial Carcinoma: A Case Report.

Nimotuzumab in the Management of Recurrent Endometrial Carcinoma: A Case Report.

Efficacy of combination chemotherapy using irinotecan and nedaplatin for patients with recurrent and refractory endometrial carcinomas: preliminary analysis and literature review

We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype. Between 2009 and 2017, 21 patients who received CPT-N therapy for recurrent endometrial carcinoma as second- or third-line chemotherapy at our hospital were identified. The CPT-N regimen included 40-70mg/m2 of CPT-11 on days 1, 8, and 15, and 50mg/m2 of nedaplatin on day 1, q4 weeks. The median patient age was 63years. The number of prior chemotherapeutic regimens ranged from 1 to 2. Two patients had prior pelvic irradiation. The response rate [ratio of complete remission (CR) to partial remission (PR)] of CPT-N therapy was 3 of 21 (14.3%), and clinical benefit rate (CBR) [the combined percentages of CR, PR, and stable disease (SD)] was 9 of 21 (42.8%). Toxicities included grade 3 neutropenia [4 (19.0%) cases], grade 3 febrile neutropenia [2 (9.5%) cases], and grade 3 diarrhea [3 (14.3%) cases]; all resolved with conservative treatment. Patients with a wild-type UGT1A1 status received higher doses of CPT-11 (p = 0.048) and had similar RR and CBR compared to those with a UGT1A1*6 and *28 status. There were no significant differences in frequencies of hematological or non-hematological toxicities, regardless of UGT1A1 status. The CPT-N regimen for recurrent and refractory endometrial carcinoma had tolerable side effects and significant efficacy. This regimen is a viable treatment option for endometrial carcinoma.

Endometrial carcinoma recurrence according to race and ethnicity: An NRG Oncology/Gynecologic Oncology Group 210 Study

Non-Hispanic black (NHB) women are more likely to experience an endometrial carcinoma (EC) recurrence compared to non-Hispanic white (NHW) women. The extent to which tumor characteristics, socioeconomic status (SES) and treatment contribute to this observation is not well defined. In the NRG Oncology/Gynecology Oncology Group (GOG) 210 Study we evaluated associations between race/ethnicity and EC recurrence according to tumor characteristics with adjustment for potential confounders. Our analysis included 3,199 NHW, 532 NHB and 232 Hispanic women with EC. Recurrence was documented during follow-up. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between race/ethnicity and EC recurrence in models stratified by histologic subtype (low-grade endometrioid, high-grade endometrioid, serous, mixed cell, carcinosarcoma, clear cell) or stage (I, II, III) and adjusted for age, SES, body mass index, smoking status and treatment. In histologic subtype-stratified models, higher EC recurrence was noted in NHB women with low-grade endometrioid (HR = 1.94, 95% CI = 1.21-3.10) or carcinosarcomas (HR = 1.66, 95% CI = 0.99-2.79) compared to NHWs. In stage-stratified models, higher EC recurrence was noted among NHB women with stage I (HR = 1.48, 95% CI = 1.06-2.05) and Hispanic women with stage III disease (HR = 1.81, 95% CI = 1.11-2.95). Our observations of higher EC recurrence risk among NHB and Hispanic women, as compared to NHW women, were not explained by tumor characteristics, SES, treatment or other confounders. Other factors, such as racial differences in tumor biology or other patient factors, should be explored as contributors to racial disparities in EC recurrence.

The Impact of Androgen Receptor Expression on Endometrial Carcinoma Recurrence and Survival.

Endometrial carcinomas (ECs) are the most common gynecologic cancers in the western world. The impact of androgen receptor (AR) on clinicopathologic parameters of EC is not well studied. The aim of our study is to assess the role of AR expression in ECs and correlate its expression with estrogen (ER) and progesterone (PR). A retrospective review of 261 EC was conducted. H&E slides were reviewed and clinicopathologic parameters were analyzed. Immunohistochemical stains for AR, ER, and PR were performed on a tissue microarray. The hormonal expression was evaluated and the data were analyzed using the Fisher exact test and Kaplan-Meier survival analysis. Patients' age ranged from 31 to 91 (median=65 y). Type I EC included 202 endometrioid and 7 mucinous carcinoma, whereas type II included 34 serous, 16 carcinosarcoma, and 2 clear cell carcinoma. Although not significant, AR expression showed more frequent association with type I EC, early tumor stage (I-II), and low FIGO grade (1-2) EC. AR expression significantly correlated with absence of lymphovascular invasion (P=0.041) and decreased LN involvement (P=0.048). Patients with AR expression showed increased disease-free survival (208 vs. 165 mo, P=0.008) and late disease recurrence (P=0.009). AR expression had a positive significant correlation with PR (P<0.001) and ER (P=0.037) expression. AR might play a role as a prognostic marker for ECs.

Clinicopathological Features of Early and Late Recurrence of Endometrial Carcinoma After Surgical Resection.

The incidence of endometrial carcinoma has been increasing annually in developed nations; it is currently the second most common gynecological malignancy. Although the majority of patients are diagnosed at an early stage, 15% to 20% reportedly recur; consequently, patients are usually followed clinically for 3 years after the initial curative surgery. We therefore aimed to determine the incidence and clinicopathological features of early and late recurrences of endometrial carcinoma after surgical resection. This retrospective study was performed using the clinical records of 2233 patients who underwent surgical resection for endometrial carcinoma between January 1970 and December 2009 at a single cancer center. Tumor recurrences were classified as early (<5 years) and late (>5 years) after initial surgery. Clinicopathological variables and tumor recurrence patterns were compared between the early and late recurrence groups. Survival analysis was performed using the Kaplan-Meier method. Among 2233 study patients, 255 (11.4%) experienced endometrial carcinoma recurrence; of these, early and late recurrences occurred in 232 (91.0%) and 23 (9.0%) patients, respectively. Late recurrence was associated with invasion of less than half of the myometrium at diagnosis and the presence of histopathological features of endometrioid adenocarcinoma with low- or intermediate-grade histological subtype and absence of lymphovascular invasion. After recurrence, there was no significant difference in overall survival between the early and late recurrence groups (P = 0.437). Furthermore, surgical treatment was associated with a significantly improved prognosis in the late recurrence group (P = 0.044). The findings of this study indicated that patients who initially underwent successful treatment for low-grade and early-stage endometrial carcinoma should be followed clinically for more than 5 years. In cases of late recurrence, surgical management may improve prognosis.

A Rare Presentation of Recurrence of Endometrial Carcinoma to Abdominal Wall: A Case Report and Review of the Literature

Introduction Endometrial carcinoma is the fourth most common carcinoma in females worldwide. Due to early symptoms, these are diagnosed at an early stage and thus have a good prognosis. Recurrences usually occur to the pelvic and para-aortic lymph nodes, vagina, peritoneum, and lungs. They occur rarely in the bones, brain, intra-abdominal organs, abdominal wall, and muscle.

Paclitaxel, Carboplatin, and Bevacizumab in Advanced and Recurrent Endometrial Carcinoma.

The aim of this study was to evaluate the efficacy of adding bevacizumab to paclitaxel and carboplatin and as maintenance in a larger cohort of patients with advanced or recurrent endometrial carcinoma. We retrospectively identified endometrial cancer patients treated with paclitaxel (175 mg/m per 3 hours), carboplatin (area under the curve, 5) and bevacizumab (15 mg/kg) and maintenance bevacizumab treated in a post-protocol treatment cohort and evaluated them with our previously published phase 2 trial of this regimen. Twenty-seven additional patients were identified; 19 received the regimen as first-line therapy, and 8 received the regimen as second-line therapy after prior paclitaxel and carboplatin. The 19 patients who received first-line therapy were analyzed alone and with the 15 patients enrolled on protocol. The 2 cohorts were similar with respect to risk factors. Overall survival curves were not statistically different between the protocol and the postprotocol patients (log-rank test; P > 0.1). Collectively, a total of 266 courses (median, 6 courses; range, 1-20 courses) of carboplatin, paclitaxel, and bevacizumab combination therapy and 305 courses (median, 16 courses; range, 0-45courses) of bevacizumab maintenance therapy were administered as first-line therapy. Collectively, the median progression-free survival was 20 months, and median overall survival was 56 months. Among 29 patients with measurable disease, the response rate was 82.8% (95% confidence interval, 69.0%-96.5%; 15 complete responses and 9 partial responses). Among the 8 patients who received paclitaxel and carboplatin and bevacizumab as second-line therapy after paclitaxel and carboplatin, the response rate was 87.5% (6 complete responses, 1 partial response). Their median progression-free survival and median overall survival were not reached after a median follow-up of 23.5 months. Although there are inherent limitations to small retrospective studies, this second analysis confirms the high response rate, progression-free survival, and overall survival in the bevacizumab, paclitaxel, and carboplatin regimen as first-line therapy in advanced and recurrent endometrial carcinoma.

Autocrine Prolactin Stimulates Endometrial Carcinoma Growth and Metastasis and Reduces Sensitivity to Chemotherapy.

Advanced and recurrent endometrial carcinoma (EC) exhibits a poor response to chemotherapy and low survival rates. It has been previously reported that human prolactin (hPRL) is upregulated in endometrial cancer and is associated with worse survival outcomes. We provide evidence for the functional role of hPRL in EC progression. We generated a model for the study of autocrine hPRL-mediated cell functional effects through the forced expression of hPRL in human EC cells. Autocrine hPRL expression stimulated cell proliferation, anchorage-independent growth, migration, and invasion of EC cells and promoted tumor growth, local invasion, and metastatic colonization in xenograft models. In addition, forced expression of hPRL decreased sensitivity of EC cells to chemotherapeutic drugs (i.e., doxorubicin and paclitaxel), both in vitro and in vivo. Consistently, small interfering RNA-mediated depletion of hPRL significantly reduced oncogenicity and enhanced the chemosensitivity of EC cells. As CD24 is hPRL-regulated and has been implicated in drug resistance in EC, we further showed that CD24 is a critical mediator of hPRL-stimulated reduced sensitivity to doxorubicin and paclitaxel in EC cells. Therefore, inhibition of hPRL signaling is a potential therapeutic strategy for the treatment of late-stage EC, which can be used in combination with chemotherapy to improve the chemotherapeutic response.

Abstract C44: Endometrial carcinoma recurrence in black and white women in the NRG Oncology/Gynecologic Oncology Group 210 trial

Abstract BACKGROUND: Black women diagnosed with endometrial carcinoma have a higher risk of recurrence compared with white women. Higher recurrence risk among black women is due, in part, to a greater frequency of aggressive tumor characteristics including non-endometrioid histologies and advanced stage tumors. The risk of recurrence for black and white women within distinct tumor groupings has not been well-examined due to low numbers of black women and under-representation of aggressive histologic subtypes in single institution studies. Therefore, we examined the association between self-reported race and recurrence risk stratified by histologic subtype in the NRG Oncology/Gynecology Oncology Group (GOG) 210, a prospective observational study that enrolled 6,124 newly diagnosed endometrial carcinoma patients between 2003 and 2011. METHODS: We restricted this analysis to 618 black and 4,316 white women with endometrial carcinoma. At study enrollment, women completed a questionnaire that assessed risk factors for gynecologic cancers. Recurrence, defined as evidence of disease following complete response to primary therapy, was abstracted from medical records. Tumor characteristics were available from surgical pathology reports and a centralized review by pathologists with expertise in gynecologic cancers. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between race (black vs. white) and recurrence risk in models stratified by histologic subtype (low-grade endometrioid, high-grade endometrioid, serous, mixed epithelial, carcinosarcoma, clear cell) and adjusted for stage (I, II, III, IV), age at diagnosis (continuous), and adjuvant therapy (none, chemotherapy, radiation, chemotherapy and radiation, unknown). We also examined income ($20,000-$39,999, $40,000-$69,999, ≥$70,000) and education (high school/GED, some college/technical school, college graduate/beyond) as potential mediators of the association between race and endometrial carcinoma recurrence risk using the Baron-Kenny method. Median follow-up time was 5 years. RESULTS: Black women were more frequently diagnosed with non-endometrioid (52.9% vs. 31.8%) and advanced stage (Stage III or IV: 29.0% vs. 21.1%) tumors compared with white women. Recurrence was documented in 26% of black and 17% of white endometrial carcinoma patients. In histologic subtype-stratified models adjusted for stage, age, and adjuvant therapy, a higher risk of recurrence was noted in black women with low-grade endometrioid (HR=1.65, 95% CI=1.07-2.54), mixed epithelial (HR=1.75, 95% CI=1.13-2.71), or carcinosarcomas (HR=1.55, 95% CI=1.03-2.31) compared with white women. No significant race-recurrence relationships were observed among women diagnosed with high-grade endometrioid, serous, or clear cell tumors. After adjustment for income and education, the association of black race and recurrence risk remained elevated, but was not statistically significant: low-grade endometrioid (HR=1.52, 95% CI=0.97-2.38), mixed epithelial (HR=1.56, 95% CI=0.98-2.50), and carcinosarcoma (HR=1.48, 95% CI=0.98-2.25). Further, neither income nor education were significantly associated with recurrence risk in the multivariable models. CONCLUSIONS: Our study provides evidence that racial disparities in endometrial carcinoma recurrence risk vary by histologic subtype. Socioeconomic factors do not explain black-white differences in endometrial carcinoma recurrence risk. Future studies exploring the role of biological factors and post-diagnosis surveillance contributing to racial differences in endometrial carcinoma recurrence are warranted. Citation Format: Ashley S. Felix, Theodore Brasky, David Cohn, Scott McMeekin, David Mutch, Creasman William, Premal Thaker, Joan Walker, Richard Moore, Shashikant Lele, Saketh Guntupalli, Levi Downs, Christa Nagel, John Boggess, Michael Pearl, Olga Ioffe, Kay Park, Shamshad Ali, Louise Brinton. Endometrial carcinoma recurrence in black and white women in the NRG Oncology/Gynecologic Oncology Group 210 trial. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C44.

Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I\u2013type II study from the GINECO group

Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma.Methods:This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety.Results:A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8–6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity.Conclusions:The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.

Prognostic Implications of Hyaluronic Acid Binding Protein 1 (HABP1) Expression, Estrogen Receptor (ER) and Progesterone Receptor (PR) Loss in Endometrial Carcinoma

Background: Endometrial carcinoma (EC) is the 4th commonest female cancer and the commonest gynecological tract malignancy. The prevalence rate is increasing; mainly in developing countries and the prognosis for recurrent or advanced EC are poor. The 5-year survival rates of EC patients are poor especially in women with metastatic EC. These bad outcomes need novel prognostic and predictive markers for EC for better managements of patients. Hyaluronic acid binding protein 1 (HABP1), which has a specific affinity toward hyaluronan (HA), was primarily discovered in cervical carcinoma (HeLa) cells. It is a eukaryotic protein conserved and ubiquitously found in multiple organisms; yeasts and humans. HABP1 expression, clinicopathological and prognostic importance in endometrial carcinoma is still not sufficiently clarified. Estrogen Receptor (ER) and Progesterone Receptor (PR) are biological molecules that have been studied as prognostic markers because of their essential physiological rules. Molecular biology advancements allow introduction of these hormone receptors to expect outcome of many cancers, e.g. ovarian, breast and EC. Aim: The aim of that study was to explore the expressions of HABP1, ER and PR in endometrial carcinoma patients, correlating their expressions with clinic-pathological factors and prognosis of patients. Methods: HABP1, ER and PR expressions were evaluated in sections from 60 paraffin blocks of EC. We analyzed correlations between the levels of markers expressions and prognosis of our patients. Results: HABP1 was expressed in 61% of EC. ER and PR were high in 56% and 63% of the patients, respectively. HABP1 expression, ER and PR loss were significantly associated with disease progression, disease free survival and poor overall survival (p=0.001, p=0.001and p=0.001, respectively). Conclusion: HABP1 high expression with ER and PR loss are markers of poor pognosis of EC patients.