scholarly journals Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial

2022 ◽  
Vol 10 (1) ◽  
pp. e003190
Author(s):  
Lukas Rob ◽  
David Cibula ◽  
Pawel Knapp ◽  
Peter Mallmann ◽  
Jaroslav Klat ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cell ◽  
Epithelial Ovarian Cancer ◽  
Tumor Antigens ◽  
First Line ◽  
Open Label ◽  
Versus Group ◽  
Gynecology And Obstetrics ◽  
Group A ◽  
Group B

BackgroundMost patients with epithelial ovarian cancer (EOC) relapse despite primary debulking surgery and chemotherapy (CT). Autologous dendritic cell immunotherapy (DCVAC) can present tumor antigens to elicit a durable immune response. We hypothesized that adding parallel or sequential DCVAC to CT stimulates antitumor immunity and improves clinical outcomes in patients with EOC. Based on the interim results of sequential DCVAC/OvCa administration and to accommodate the increased interest in maintenance treatment in EOC, the trial was amended by adding Part 2.MethodsPatients with International Federation of Gynecology and Obstetrics stage III EOC (serous, endometrioid, or mucinous), who underwent cytoreductive surgery up to 3 weeks prior to randomization and were scheduled for first-line platinum-based CT were eligible. Patients, stratified by tumor residuum (0 or <1 cm), were randomized (1:1:1) to DCVAC/OvCa parallel to CT (Group A), DCVAC/OvCa sequential to CT (Group B), or CT alone (Group C) in Part 1, and to Groups B and C in Part 2. Autologous dendritic cells for DCVAC were differentiated from patients’ CD14+ monocytes, pulsed with two allogenic OvCa cell lines (SK-OV-3, OV-90), and matured in the presence of polyinosinic:polycytidylic acid. We report the safety outcomes (safety analysis set, Parts 1 and 2 combined) along with the primary (progression-free survival (PFS)) and secondary (overall survival (OS)) efficacy endpoints. Efficacy endpoints were assessed in the modified intention-to-treat (mITT) analysis set in Part 1.ResultsBetween November 2013 and March 2016, 99 patients were randomized. The mITT (Part 1) comprised 31, 29, and 30 patients in Groups A, B, and C, respectively. Baseline characteristics and DCVAC/OvCa exposure were comparable across the treatment arms. DCVAC/OvCa showed a good safety profile with treatment-emergent adverse events related to DCVAC/OvCa in 2 of 34 patients (5.9%) in Group A and 2 of 53 patients (3.8%) in Group B. Median PFS was 20.3, not reached, and 21.4 months in Groups A, B, and C, respectively. The HR (95% CI) for Group A versus Group C was 0.98 (0.48 to 2.00; p=0.9483) and the HR for Group B versus Group C was 0.39 (0.16 to 0.96; p=0.0336). This was accompanied by a non-significant trend of improved OS in Groups A and B. Median OS was not reached in any group after a median follow-up of 66 months (34% of events).ConclusionsDCVAC/OvCa and leukapheresis was not associated with significant safety concerns in this trial. DCVAC/OvCa sequential to CT was associated with a statistically significant improvement in PFS in patients undergoing first-line treatment of EOC.Trial registration numberNCT02107937, EudraCT2010-021462-30.

The Role of HE4, a Novel Biomarker, in Predicting Optimal Cytoreduction After Neoadjuvant Chemotherapy in Advanced Ovarian Cancer

2017 ◽  
Vol 27 (4) ◽  
pp. 696-702 ◽  
Author(s):  
Francesco Plotti ◽  
Giuseppe Scaletta ◽  
Stella Capriglione ◽  
Roberto Montera ◽  
Daniela Luvero ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Advanced Ovarian Cancer ◽  
Debulking Surgery ◽  
Gynecology And Obstetrics ◽  
Group A ◽  
Group B

ObjectivesThis study aimed to evaluate serum human epididymis protein 4 (HE4) changes during neoadjuvant chemotherapy (NACT) to establish HE4 predebulking surgery cutoff values and to demonstrate that CA125, HE4, and computed tomography (CT) taken together are better able to predict complete cytoreduction after NACT in advanced ovarian cancer patients.MethodsFrom January 2006 to November 2015, patients affected by epithelial advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III–IV), considered not optimally resectable, were included in this prospective study. After 3 cycles of NACT, all patients underwent debulking surgery and were allocated, according to residual tumor (RT), into group A (RT = 0) and group B (RT > 0). Serum CA125, HE4, and CT images were recorded during NACT and compared singularly and with each other in term of accuracy, sensitivity, specificity, and positive and negative predictive value.ResultsA total of 94 and 20 patients were included in group A and group B, respectively. The HE4 values recorded before debulking surgery correlated with RT. The identified HE4 cutoff value of 226 pmol/L after NACT was able to classify patients at high or low risk of suboptimal surgery, with a sensitivity of 75% and a specificity of 85% (positive predictive value, 0.87; negative predictive value, 0.70). The combination of CA125, HE4, and CT imaging resulted in the best combination with a sensitivity of 96% and a specificity of 92% (positive predictive value, 0.96; negative predictive value, 0.94).ConclusionsThe novel biomarker HE4, in addition to CA125 and CT, is better able to predict the RT at debulking surgery and the prognosis of patients.

scholarly journals Survival and Side Effects of Cisplatin/Cyclophosphamide and Carboplatin/Paclitaxel Adjuvant Chemotherapy in Stage IC-IV Ovarian Cancer

2016 ◽  
Author(s):  
Unedo H Markus ◽  
Hariyono Winarto ◽  
Andrijono Andrijono ◽  
Bambang Sutrisna
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Side Effects ◽  
Adjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Group A ◽  
Group B

Objective: To compare the survival and side effects in epithelial ovarian cancer patients receiving adjuvant chemotherapy of cisplatin/ cyclophosphamide and carboplatin/paclitaxel. Method: We recruited epithelial ovarian cancer patients receiving cisplatin/cyclophosphamide (group A) or carboplatin/paclitaxel (group B) adjuvant chemotherapy after surgery. Chemotherapy was given for six cycles. Overall survival and side effects were assessed. Result: A total of 49 patients were recruited, consisting of 25 patients for group A and 24 patients for group B. In this study, the overall survival of stage IC-IV ovarian cancer patients was 37.3 months in group A (95%CI=31.86-43.46) and 35.5 months (95%CI= 13.93- 43.46) in group B (p

Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment

2004 ◽  
Vol 22 (6) ◽  
pp. 1040-1044 ◽  
Author(s):  
Viviane Hess ◽  
Roger A'Hern ◽  
Nazar Nasiri ◽  
D. Michael King ◽  
Peter R. Blake ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Specific Treatment ◽  
Progression Free Survival ◽  
Controlled Study ◽  
First Line ◽  
Gynecology And Obstetrics ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Histologic Subtypes

Purpose Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. Patients and Methods Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. Results Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P = .01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P = .009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P < .001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P < .001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P < .001) and 3.08 (95% CI, 1.69 to 5.6; P < .001), respectively, for mEOC patients as compared with controls. Conclusion Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.

Patterns of Recurrence in Patients Treated With Bevacizumab in the Primary Treatment of Advanced Epithelial Ovarian Cancer

2013 ◽  
Vol 23 (7) ◽  
pp. 1219-1225 ◽  
Author(s):  
Jose Alejandro Rauh-Hain ◽  
Stephanie H. Guseh ◽  
Katharine M. Esselen ◽  
Whitfield B. Growdon ◽  
John O. Schorge ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Primary Treatment ◽  
Categorical Variables ◽  
First Line ◽  
Liver Recurrence ◽  
First Recurrence ◽  
Patterns Of Recurrence ◽  
First Line Treatment ◽  
Registry Database

ObjectiveThe purpose of this study was to compare the distribution of the first site of recurrence in patients with epithelial ovarian cancer (EOC) who received first-line treatment with bevacizumab compared with patients who did not receive bevacizumab.MethodsFrom the Cancer Registry database at our institutions, we identified a group of patients with recurrent EOC who underwent treatment from January 1, 2005, to December 31, 2010. Each patient record was evaluated to classify the site of first recurrence. Correlation between categorical variables was assessed with χ2test.ResultsTwo hundred ninety-two patients with advanced EOC (stage III or IV) who originally responded to chemotherapy and had a recurrence were identified. Of these, 37 (12.5%) had received postoperative chemotherapy bevacizumab, and 255 (87.5%) did not. Compared with those not treated with bevacizumab, there was a lower incidence of liver recurrence (0% vs 9%;P= 0.05) and a higher rate of lung and/or pleural recurrence (22% vs 5%;P= 0.001) and recurrence at distant sites (22% vs 9%;P= 0.03) in patients who received bevacizumab. There was no difference in the incidence of ascites at the time of recurrence between these groups.ConclusionsPatients who received bevacizumab as part of primary treatment for EOC had a higher rate of lung and/or pleural recurrence and a lower rate of liver recurrence. There was no difference in the rate of ascites at the time of recurrence.

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