scholarly journals A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician’s choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA)

2020 ◽  
Vol 30 (8) ◽  
pp. 1239-1242
Author(s):  
Natalie YL Ngoi ◽  
Valerie Heong ◽  
Samuel Ow ◽  
Wen Yee Chay ◽  
Hee Seung Kim ◽  
...  
Keyword(s):  
Sample Size ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Immune Checkpoint ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Oncology Group ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival

BackgroundThe optimal treatment of recurrent ovarian clear cell carcinoma remains unknown. There is increasing rationale to support the role of immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in ovarian clear cell carcinoma.Primary objectiveTo evaluate the efficacy of durvalumab (MEDI-4736) compared with standard chemotherapy in patients with recurrent ovarian clear cell carcinoma.Study hypothesisPatients with recurrent ovarian clear cell carcinoma treated with durvalumab will have improved progression-free survival compared with those treated with chemotherapy of physician’s choice.Trial designThe MOCCA study is a multicenter, open-label, randomized phase II trial in patients with recurrent ovarian clear cell carcinoma, which recruited from eight sites across Gynecologic Cancer Group Singapore (GCGS), Korean Gynecologic-Oncology Group (KGOG), and Australia New Zealand Gynecological Oncology Group (ANZGOG). Enrolled patients were randomized in a 2:1 ratio to receive durvalumab or physician’s choice of chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent.Major inclusion/exclusion criteriaEligible patients required histologically documented diagnosis of recurrent ovarian clear cell carcinoma, as evidenced by WT1 negativity. All patients must have been of Eastern Cooperative Oncology Group (ECOG) performance status 2 or better, and have had previous treatment with, and progressed or recurred after prior platinum-based chemotherapy. No more than four prior lines of treatment were allowed and prior immune checkpoint inhibitor treatment was not permitted.Primary endpointsThe primary endpoint was the median progression-free survival following treatment with durvalumab, compared with physician’s choice of chemotherapy. Progression-free survival was defined as the time from the first day of treatment to the first observation of disease progression, or death due to any cause, or last follow-up.Sample sizeThe target sample size was 46 patients.Estimated dates for completing accrual and presenting resultsAccrual has been completed and results are expected to be presented by mid-2021.Trial registrationClinicaltrials.gov: NCT03405454.

scholarly journals Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma

2011 ◽  
Vol 25 (2) ◽  
pp. 282-288 ◽  
Author(s):  
Atsuko Katagiri ◽  
Kentaro Nakayama ◽  
Mohammed Tanjimur Rahman ◽  
Munmun Rahman ◽  
Hiroshi Katagiri ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival

scholarly journals Mismatch Repair Status as a Predictor of Benefit From Platinum-Based Adjuvant Therapy in Ovarian Clear Cell Carcinoma

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 217s-217s
Author(s):  
J. Zhu ◽  
X. Wu ◽  
X. Ju
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival ◽  
Pathologic Features

Background: Previous studies have indicated that patients with colorectal cancer who demonstrate defective DNA mismatch repair (dMMR) have clinical and pathologic features that distinguish them from patients who have proficient mismatch repair (pMMR) tumors. However, the influence of mismatch repair (MMR) status in ovarian clear cell carcinoma (OCCC) is still unknown. Aim: To evaluate the MMR statuses in OCCC and its correlation with clinicopathological and prognostic characteristics. Methods: MMR statuses were measured by tissue microarray–based immunohistochemistry from 120 OCCC patients. The associations of clinicopathologic features with progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed by Cox regression model. Results: Overall, 120 OCCC patients met the entry criteria and their MMR status were detected, consisting of 24 patients with dMMR and 96 patients with pMMR. Tumors with dMMR were strongly associated with platinum-sensitive disease ( P = 0.008) and large tumor volume ( P = 0.028). Among all the patients who have received surgery, tumors with dMMR had a better progression-free survival and overall survival (OS) than those with pMMR (hazard ratio [HR] for recurrence, 0.459 [95% confidence interval (95% CI), 0.224-0.940]; P = 0.029; HR for death, 0.381 [95% CI, 0.170-0.853]; P = 0.015). In subgroup analysis, dMMR patients experienced a better PFS (HR, 0.242; P = 0.055) and OS (HR, 0.141; P = 0.039) than pMMR cases among early stages (I-II), but this difference was not observed in advanced stage (III-IV) patients. Meanwhile, pMMR was associated with more favorable prognosis than dMMR in platinum-resistant patients (PFS, HR: 0.317, P = 0.052; OS, HR: 0.370, P = 0.046). Multivariate analysis revealed that only advanced stages (III-IV) were adverse independent prognosticators for both PFS (HR, 5.938; [95% CI, 2.804-12.574], P < 0.001) and OS (HR, 6.209; [95% CI, 2.724-14.156], P < 0.001). Conclusion: MMR status in ovarian clear cell carcinoma is not only a prognostic indicator, but also appears to be a possible predictor for the use of platinum-based adjuvant chemotherapy.

Effect of bevacizumab in first-line chemotherapy on progression-free survival in advanced ovarian clear cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18086-e18086
Author(s):  
Shinichi Tate ◽  
Kyoko Nishikimi ◽  
Ayumu Matsuoka ◽  
Makio Shozu
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Survival Outcome ◽  
Wilcoxon Test ◽  
Ovarian Clear Cell Carcinoma ◽  
First Line ◽  
Free Survival ◽  
Line Chemotherapy

e18086 Background: Advanced ovarian clear cell carcinoma (ACCC, stage III/IV disease) is a rare tumor characterized by chemoresistance. To evaluate the efficacy of bevacizumab (Bev) for ACCC, we investigated the survival outcome of first-line treatment before and after the approval of Bev for ovarian cancer treatment in November 2013 in Japan. Methods: We recruited 28 consecutive patients diagnosed with ACCC at our institution between 2007 and 2018. We performed cytoreductive surgery and administered paclitaxel-carboplatin chemotherapy (paclitaxel: 80 mg/m2 + carboplatin area under the curve 2.0–3.0 mg/mL/min, weekly without break) as first-line chemotherapy. Bev (15 mg/kg/3 weeks) was also administered after its approval. We compared progression-free survival (PFS) between Bev+ group (n = 18) and Bev- group (n = 10) using the Kaplan–Meier method and a Cox regression model. Results: Patients characteristics were similar between the Bev- and Bev+ groups. The median age was 54 years and 53 in the Bev- and Bev+ groups (p = 0.810), respectively. Three (30%) and 4 (22%) patients in the Bev- and Bev+ groups had stage IV disease (p = 0.674), respectively. The performance status (PS) was ≥2 in 1(10%) and 5 (28%) patients in the Bev- and Bev+ groups (p = 0.375), respectively. Peritoneal cancer index was 5.5 and 5.5 in the in Bev- and Bev+ groups (p = 0.727), respectively. Primary debulking surgery was performed in 10 (100%) and 11 (61%) patients in the Bev- and in Bev+ groups, respectively. Surgical complexity score was 9 and 9 in the Bev- and in Bev+ groups (p = 0.700), respectively. Completeness of resection was higher in the Bev- group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev+ group received ≥21 cycles of Bev. The median PFS increases from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis revealed that Bev use (p = 0.005) and PS < 2 (p = 0.035) were independent prognostic factors for PFS; however, completeness of resection was not a prognostic factor (p = 0.052). Conclusions: Bev in first-line chemotherapy improves the survival outcome of ACCC. [Table: see text]

The potential of gemcitabine, cisplatin, and bevacizumab combination therapy for patients with ovarian clear cell carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17065-e17065
Author(s):  
Kimihiko Ito ◽  
Mio Nakagawa ◽  
Lena Tashima ◽  
Taro Yagi ◽  
Chihiro Odani ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cell Carcinoma ◽  
Standard Treatment ◽  
Response Rate ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Ovarian Clear Cell Carcinoma ◽  
Platinum Sensitive ◽  
Institutional Ethics

e17065 Background: Patients with advanced ovarian clear cell carcinoma (OCC) have poor prognosis, and response rate of chemotherapy for relapsed OCC is less than 10%. The effective standard treatment has not been established yet. The synergic effect between gemcitabine and cisplatin in ovarian cancer patients has been reported. And bevacizumab added on chemotherapy has some evidences of progression-free survival improvement at primary, platinum sensitive relapse and platinum resistant relapse situation than chemotherapy only. Therefore, we conducted a retrospective charts review to examine the safety and efficacy of gemcitabine, cisplatin, and bevacizumab combination (GPB) therapy in OCC patients treated in our hospital. Methods: Intravenous gemcitabine (1,000 mg/m2, day 1, 15), cisplatin (40 mg/m2, day 1, 15), and bevacizumab (15 mg/kg, day 1) were administrated every 28 days. This combination therapy was continued until disease progression or appearance of intolerable toxicity. This retrospective study was approved by our institutional ethics board. Results: Eight patients were treated with this GPB therapy in our institution between April 2013 and August 2015. Six patients received this therapy due to presence of relapse, and 2 patients were administered GPB as post-operative adjuvant therapy. Four patients were not treated with bevacizumab due to their medical conditions. The median treatment cycle was 5.5 (range: 1-15). Six patients were evaluable and their responses were partial response (PR) 1, stable disease (SD) 2, and progressive disease (PD) 3. The overall response rate was 13% and the disease control rate was 50%. Four patients needed dose reduction or treatment delay. Grade 3 adverse events observed were anemia (25%), nausea (13%), and elevation of G-GTP (13%). Conclusions: GPB therapy is feasible and moderately effective for patients with OCC. We are currently conducting the prospective multi-institutional phase II trial (UMIN 000023097) and expect that GPB therapy will be used as the standard treatment regimen for OCC, in future.

Adjuvant Chemotherapy for Stage I Ovarian Clear Cell Carcinoma: Is it Necessary for Stage IA?

2012 ◽  
Vol 22 (7) ◽  
pp. 1143-1149 ◽  
Author(s):  
Mika Mizuno ◽  
Hiroaki Kajiyama ◽  
Kiyosumi Shibata ◽  
Kimio Mizuno ◽  
Osamu Yamamuro ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Stage I ◽  
Surgical Staging ◽  
Recurrence Free Survival ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival ◽  
Stage Ia

BackgroundIt is controversial whether patients with stage I ovarian clear cell carcinoma (CCC) benefit from postoperative chemotherapy. This study was designed to evaluate the postoperative outcomes associated with the inclusion or exclusion of adjuvant therapy in these patients.MethodsA total of 185 patients who were treated for stage I CCC between 1991 and 2007 were retrospectively evaluated. All of the patients had received comprehensive surgical staging, and their condition had been diagnosed by a central pathological review system. Only one patient with stage IB was excluded from this study.ResultsMedian follow-up time was 62 months (range 7–191 months). Median age was 52 years (30–75 years). There were 41, 93, and 50 patients in stage IA, intraoperative capsule ruptured IC (rupture-IC), and all other-IC groups, respectively. The 5-year recurrence-free survival rates for the substage were 97.6%, 87.8%, and 70.4% (P < 0.001), respectively. Among 134 patients consisting of those in the stage IA and rupture-IC groups, 91 patients received adjuvant chemotherapy (AC) and 43 patients did not (non-AC). There was no significant survival difference in each substage group between the non-AC and AC groups in 5-year recurrence-free survival rate (stage IA, 100% vs 93.8%; rupture-IC, 94.1% vs 86.6%). Multivariate analysis demonstrated that there was no significant prognostic factor for both recurrence and survival among the IA and rupture-IC groups. Postoperative therapy, regimen, and chemotherapy cycles were not significantly affected.ConclusionsThis study indicates that adjuvant chemotherapy does not contribute to the improving prognosis of stage IA ovarian CCC. Whereas the histological type is CCC, the routine adjuvant chemotherapy after comprehensive surgical staging may be unnecessary for patients with at least stage IA.

scholarly journals The Frequency and Clinical Implication of Mismatch Repair Protein Deficiency in Chinese Patients with Ovarian Clear Cell Carcinoma

2021 ◽  
Author(s):  
Shuang Ye ◽  
Shuling Zhou ◽  
Siyuan Zhong ◽  
Boer Shan ◽  
Wenhua Jiang ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Early Stage ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Ovarian Clear Cell Carcinoma ◽  
Early Stage Disease ◽  
Platinum Sensitive

Abstract Background: To assess the prevalence of deficient mismatch repair (MMR) in Chinese ovarian clear cell carcinoma (CCC) patients and its association with clinicopathologic features.Methods: Immunohistochemistry with four antibodies against MLH1, PMS2, MSH2 and MSH6 were performed on whole section slides. Results were correlated with clinicopathologic variables.Results: A total of 108 cases were included in the study, with a median age of 52 years at first diagnosis. Early-stage disease and platinum-sensitive recurrence accounted for 62.3% and 69.6%, respectively. Overall, the estimated 5-year overall survival was 70.3% and 20.7% in patients with early and late stage tumor, respectively. Deficient MMR were identified in 5.6% (6/108) of the cohort and included MSH2/MSH6 (n=4) and MLH1/PMS2 (n=2). The average age of the six patients was 45.6 years. The rate of MMR-deficient tumors in women ≤ 50 years was relatively higher than that those over 50 years (10.0% Vs. 2.9%; P=0.266). A half of the patients with deficient MMR were diagnosed with a synchronous (endometrial or colorectal) and metachronous (endometrial) cancer, significantly more than those intact counterparts (P=0.002). All the six patients had early-stage tumor and the majority (83.3%) were platinum-sensitive. The median progression-free survival was slightly higher in patients with defective MMR expression than those intact counterparts (30 months Vs. 27 months), although significance was not achieved (P=0.471). Conclusions: Ovarian CCC patients with young age and concurrent diagnosis of endometrial and colorectal cancer are more likely to have MMR-deficient tumors. It merits further evaluation whether patients harboring MMR abnormality has favorable prognosis.

scholarly journals Bevacizumab in First-Line Chemotherapy Improves Progression-Free Survival for Advanced Ovarian Clear Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3177
Author(s):  
Shinichi Tate ◽  
Kyoko Nishikimi ◽  
Ayumu Matsuoka ◽  
Satoyo Otsuka ◽  
Yuki Shiko ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Performance Status ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Wilcoxon Test ◽  
First Line ◽  
Free Survival ◽  
Line Chemotherapy

(1) Background: We investigated survival outcomes following first-line chemotherapy before and after approval of bevacizumab (Bev) for ovarian cancer in Japan to evaluate the efficacy of Bev for advanced clear cell carcinoma (CCC). (2) Methods: We investigated 28 consecutive patients diagnosed with CCC (stages III/IV) at our hospital between 2008 and 2018. Bev was administered for treatment of advanced CCC after approval in Japan in November 2013. Progression-free survival (PFS) was compared between 10 patients treated before Bev approval (2008–2013, Bev- group) and 18 patients treated after Bev approval (2014–2018, Bev+ group) for first-line chemotherapy. (3) Results: No intergroup difference was observed in patient characteristics. The rate of completeness of resection was higher in the Bev − group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev + group received ≥ 21 cycles of Bev. The median PFS increased from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis showed that performance status (p = 0.049), Bev administration (p = 0.023) and completeness of resection (p = 0.023) were independent prognostic factors for PFS. (4) Conclusions: Bev incorporated into first-line chemotherapy might improve PFS in patients with advanced CCC. We hope that our findings will be confirmed in adequate clinical trials.

Impact of the number of removed lymph nodes on recurrence-free survival in stage I ovarian clear cell carcinoma

2018 ◽  
Vol 23 (5) ◽  
pp. 930-935 ◽  
Author(s):  
Yuji Takei ◽  
Suzuyo Takahashi ◽  
Shizuo Machida ◽  
Akiyo Taneichi ◽  
Takahiro Yoshiba ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Stage I ◽  
Recurrence Free Survival ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival

scholarly journals The impact of lymphadenectomy on survival outcomes of ovarian clear cell carcinoma: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Yan Liu ◽  
Changzhen Huang ◽  
Ran Chu ◽  
Xingsheng Yang ◽  
Beihua Kong ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival ◽  
The Impact

Background: The treatment strategies for ovarian clear cell carcinoma (OCCC) are the same as those for epithelial ovarian cancer. Due to the rarity of OCCC, no prospective studies of its surgery have been reported. Therefore, the therapeutic significance of lymphadenectomy for OCCC needs to be further clarified. Objectives: To assess the effectiveness of lymphadenectomy in patients with ovarian clear cell carcinoma by a meta-analysis. Search Strategy: The Web of Science, Scopus, PubMed, and other sources (e.g. Google Scholar) were searched from each database’s earliest inception to June 2021. Selection Criteria: English-language publications of observational studies that investigated the role of lymphadenectomy in patients with OCCC were included. Data Collection and Analysis: The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated. Main Results: The analysis demonstrated that lymphadenectomy is associated with significantly improved disease-specific survival (DSS) (HR=0.76; 95%CI=0.60-0.95; P=0.02; I2= 0.0%) and disease-free survival (DFS) (HR=0.58; 95%CI=0.33-1.00; P=0.05; I2=61%), but not for overall survival (OS) (HR=0.80; 95%CI=0.60-1.06; P=0.12; I2= 19%) and progression-free survival (PFS) (HR=0.95; 95%CI=0.64-1.42; P=0.79; I2= 0.0%). But it is worth noting that several single studies indicated a tendency of improved OS, PFS, DFS, DSS with lymphadenectomy. Conclusions: Lymphadenectomy could not significantly improve OS and PFS for OCCC, but is associated with improved DFS and DSS. Gynecologic oncologists should tailor treatment to patients to achieve optimal outcomes. And further studies are necessary to validate the impact of lymphadenectomy on OCCC. Keywords: ovarian clear cell carcinoma, lymphadenectomy, survival, systematic review, meta- analysis

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