Chemotherapy For Advanced Ovarian Cancer Research Articles

Intraperitoneal Nivolumab after Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy in Advanced Ovarian Cancer: A Phase I Study with Expansion Cohort.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are expected to be synergistic with intraperitoneal (IP) immunotherapy by increasing tumor antigen expression and mutational load. We assessed the feasibility and safety of IP nivolumab following complete CRS and HIPEC in pretreated patients with recurrent ovarian cancer (ClinicalTrials.gov identifier: NCT03959761). Patients received IP nivolumab (0.5, 1, or 3 mg/kg) using a 3 + 3 dose-escalation design, starting 5 to 7 days after CRS and HIPEC. Four IP Q2W (once every 2 weeks) nivolumab infusions were planned. The primary objective was to demonstrate the feasibility of IP nivolumab based on dose-limiting toxicity. Secondary objectives were to assess changes in tolerance of CRS and HIPEC. A total of 17 patients were enrolled including 10 patients in the dose escalation and 7 patients in the expansion phase. No dose-limiting toxicity was observed at any dose level in the 9 evaluable patients. Six of the 17 patients (35%) did not complete all planned infusions: 4 (23.5%) due to peritoneal catheter complications and 2 (11.8%) due to early progression. No procedure-related deaths occurred. Eleven patients (65%) experienced serious adverse events (SAE), mainly transitory grade 3 to 4 transaminase elevations (6/11) and surgery-related (9/11). Four SAEs were related to the peritoneal catheter and two to HIPEC. No SAEs/grade 3 to 4 adverse events related to IP nivolumab occurred. This is the first study demonstrating the feasibility of IP nivolumab in patients with relapsed advanced ovarian cancer. Further investigation at 3 mg/kg is warranted.

Clinical value of serum tumor markers in assessing the efficacy of neoadjuvant chemotherapy in advanced ovarian cancer: single-center prospective clinical study.

This study aimed to assess the clinical importance of various biomarkers, including NLR, CEA, CA199, CA125, CA153, and HE4, through dynamic testing to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) for individuals facing advanced ovarian cancer. This provides valuable information for tailoring treatment plans to individual patients, thereby leading to a more personalized and effective management of individuals facing ovarian cancer. The levels of NLR, CA125, CA199, CEA, CA153, and HE4 were detected before chemotherapy and after 3 courses of chemotherapy. Patients were categorized into ineffective and effective groups according to the effectiveness of NACT. To evaluate the factors influencing NACT's effectiveness in individuals facing advanced ovarian cancer, receiver operating characteristic (ROC) curves, predictive modeling, and multifactorial regression analysis were employed. In the effective group, the patients' age, maximum tumor diameter, and CEA and HE4 levels of the patients were significantly higher compared to those in the ineffective group (P <.05). Additionally, the difference in HE4 levels before and after treatment between the effective and ineffective groups was statistically significant (P<.05). Multifactorial analysis showed that age and maximum tumor diameter were independent risk factors impacting the effectiveness of NACT in individuals facing advanced ovarian cancer (P<.05). The ROC curve for predicting the effectiveness of NACT in individuals facing advanced ovarian cancer showed a sensitivity of 93.3% for NLR and a specificity of 92.3% for CA199. HE4 emerged as the most reliable predictor, demonstrating a specificity of 84.6% and a sensitivity of 75.3%. The area under the curve of the combined CA125 and HE4 assays for predicting the ineffectiveness of NACT in individuals facing advanced ovarian cancer was 0.825, showcasing a specificity of 74.2% and a sensitivity of 84.6%. The predictive capacity for the effectiveness of NACT in individuals facing advanced ovarian cancer is notably high when considering the sensitivity of NLR and the specificity of CA199. Additionally, the combination of CA125 and HE4 assays can obtain a better predictive effect, which can accurately select patients suitable for NACT, determine the appropriate timing of the interval debulking surgery (IDS) surgery, and achieve a satisfactory tumor reduction effect.

Prospective validation of the role of PET/CT in detecting disease after neoadjuvant chemotherapy in advanced ovarian cancer

ObjectivesThe study aimed to compare the diagnostic accuracies of 2-[18F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC).Materials and methodsThis study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III–IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar’s test.ResultsIn the historical cohort (23 patients, age 58 ± 13), 2-[18F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[18F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05).Conclusion2-[18F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC.Clinical relevance statement2-[18F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery.Key Points• Additional value of 2-[18F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy.• 2-[18F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT.• Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy.

Oncological outcomes of intraperitoneal chemotherapy in advanced ovarian cancer: BRCA mutation role

IntroductionThe knowledge of BRCA status offers a chance to evaluate the role of the intraperitoneal route in patients selected by biomolecular profiles after primary cytoreduction surgery in advanced ovarian cancer. Materials and methodsWe performed a retrospective, multicenter study to assess oncological outcomes depending on adjuvant treatment (intraperitoneal [IP] vs intravenous [IV]) and BRCA status (BRCA1/2 mutated vs. BRCA wild type [WT]). The primary endpoint was to determine progression-free survival. The secondary objectives were overall survival and toxicity. ResultsA total of 288 women from eight centers were included: 177 in the IP arm and 111 in the IV arm, grouped into four arms according to BRCA1/2 status. Significantly better PFS was observed in BRCA1/2-mutated patients with IP chemotherapy (HR: 0.35; 95% CI, 0.16–0.75, p = 0.007), which was not present in BRCA1/2-mutated patients with IV chemotherapy (HR: 0.65; 95% CI, 0.37–1.12, p = 0.14). Significantly better OS was also observed in IP chemotherapy (HR: 0.17; 95% CI, 0.06–043, p < 0.0001), but was not present in IV chemotherapy in relation with BRCA mutation (HR: 0.52; 95% CI, 0.22–1.27, p = 0.15). For BRCA WT patients, worse survival was observed regardless of the adjuvant route used. The IP route was more toxic compared to the IV route, but toxicity was equivalent at the long-term follow-up. ConclusionThis retrospective study suggests that BRCA status can help to offer an individualized, systematic treatment after optimal primary surgery for advanced ovarian cancer, but is limited by the small sample size. Prospective trials are essential to confirm these results.

Safety and feasibility of therapeutic anticoagulation for newly diagnosed venous thromboembolism in women who undergo neoadjuvant chemotherapy for advanced ovarian cancer

ObjectiveWe sought to investigate the safety and feasibility of therapeutic anticoagulation for newly diagnosed venous thromboembolism among women who undergo neoadjuvant chemotherapy for the treatment of advanced ovarian cancer.MethodsA retrospective...

The use of intraperitoneal chemotherapy for advanced ovarian cancer - The experience of a tertiary referral centre.

Platinum-based chemotherapy is the backbone of the medical management of ovarian cancer. The dose, route and timing of treatment are ongoing areas of debate. Intraperitoneal (IP) chemotherapy is an alternative delivery method treatment to the conventional intravenous (IV) route for patients with epithelial ovarian cancer, with efficacy supported by Level 1 evidence. To compare the outcomes and feasibility of IP to IV delivery of platinum-based chemotherapy in patients with advanced epithelial ovarian cancer. In a single institution, patients receiving adjuvant chemotherapy (IP and IV) for Stages III and IV epithelial ovarian cancer over the period January 2006-December 2018 were identified through a prospectively maintained database. All patients with an IP port inserted were included. A control group of patients treated with IV chemotherapy was created using criteria identified during the study and in the randomised trials that tested IP chemotherapy. Assessments were made for relapse-free survival (RFS) and overall survival (OS) for each cohort. A total of 639 patients received adjuvant chemotherapy (73 IP and 566 IV) during the study period. Both the IP group and matched IV control group (65 patients) had a median RFS of 26 months. The median OS in the IP group was 63.9 months, and in the IV group was 57.2 months. At ten years, a significantly higher proportion of patients were alive in the IP group cohort (16% vs 3%, relative risk 5.5, 95% CI 1.29-24, P = 0.012). IP chemotherapy was well tolerated by our cohort. In the IP group, 73% had four or more IP cycles and 99% received six or more cycles of chemotherapy. Our cohort had a high rate of completion of IP chemotherapy with excellent rates of completion of six cycles of any treatment. The RFS and OS in the IP chemotherapy group were comparable to each other and reflected those in the published literature. A significantly higher proportion of patients in the IP cohort were alive at ten years than in the IV cohort.

AGO-OVAR 28/ENGOT-ov57. Niraparib alone versus niraparib in combination with bevacizumab in patients with carboplatin-taxane-based chemotherapy in advanced ovarian cancer: a multicenter randomized phase III trial

BackgroundPhase III trial data have shown a significant benefit by the addition of a maintenance treatment with niraparib, irrespective of BRCA or HRD status, in patients with advanced high-grade ovarian...

Cost-effectiveness of poly-(ADP-ribose) polymerase (PARP)-inhibitors for the maintenance treatment after responding to first- and second-line chemotherapy in advanced ovarian cancer.

The introduction of inhibitors of poly-(ADP-ribose) polymerase (PARP) for the treatment of women with epithelial ovarian cancers (EOC) has radically changed the treatment in maintenance setting after responding to first- and second-line chemotherapy. The aim of this paper was to assess the pharmacological costs of PARP inhibitors (olaparib, niraparib, rucaparib and veliparib) in maintenance treatment after responding to first-line chemotherapy in EOC. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression-free survival (PFS)). We have considered the pivotal phase III randomized controlled trials (RCTs). Three different populations were considered: the overall population, patients with germline BRCA mutation (gBRCA) and homologous recombination deficiency (HRD) patients non-gBRCA mutation. Three thousand four hundred and twenty patients and 1209 patients were considered in maintenance treatment after responding to first- and second-line chemotherapy in EOC, respectively. At the actual price, the treatment with PARP inhibitors is not cost-effective in maintenance treatment after responding to first-line and second-line chemotherapy in EOC. A reduction in pharmacological costs is mandatory.

Impact of venous thromboembolism on timing and outcomes of interval debulking surgery among patients treated with neoadjuvant chemotherapy for advanced ovarian cancer (370)

Impact of venous thromboembolism on timing and outcomes of interval debulking surgery among patients treated with neoadjuvant chemotherapy for advanced ovarian cancer (370)

A nomogram to predict progression-free survival benefit with maintenance olaparib and bevacizumab following response to first line chemotherapy in advanced ovarian cancer (305)

<b>Objectives:</b> Maintenance treatment with either bevacizumab or poly(ADP ribose) polymerase inhibitors or both are options in advanced ovarian cancer. The PAOLA-1/ENGOT-ov25 trial (NCT02477644) found that combinatory olaparib-bevacizumab in addition to chemotherapy significantly prolonged progression-free survival (PFS) over chemotherapy and bevacizumab alone in an unselected patient population, with greater benefit in those with homologous recombination deficiency (HRD) tumor (including s<i>BRCA</i> mutation or not). The objective of this study was to develop a nomogram to better predict the PFS for patients receiving either olaparib-bevacizumab or bevacizumab. <b>Methods:</b> Using data from the PAOLA-1 trial, we performed multivariable Cox regression analysis based on baseline factors to develop a nomogram that predicts PFS. A total of 15 variables were evaluated. Each patient was then assigned a score that ranged from 0 to 100, and they were grouped into quartiles based on their risk of recurrence. We evaluated the discriminatory value of the risk categorization using the Kaplan-Meier approach and Harrell's discrimination concordance index. <b>Results:</b> FIGO Stage III, CA-125 ≤25 U/ml, primary debulking surgery with no macroscopic residual disease, complete response after chemotherapy, HRD, and olaparib-bevacizumab treatment were associated with longer PFS. The scores for good, medium-1, medium-2 and poor prognosis groups were 0-25, 26-50, 51-65, and 66-100, respectively. The nomogram showed good discrimination (C-index 0.71). Median PFS (mPFS) of model-predicted risk groups were significantly different (p<0.001, Figure A): good, (<i>n</i>=205, 39.3) (95% CI: 36.0-NR), medium-1 (<i>n</i>=201, 23.8) (95% CI: 21.9-26.1), medium-2 (<i>n</i>=201, 17.6) (95% CI: 16.0-20.3), and poor (<i>n</i>=198, 11.1) (95% CI: 10.3-13.9). When the model was applied only in patients with HRD tumors and treated with olaparib-bevacizumab, there were no patients with poor risk. For these patients (Figure B), the mPFS were good (<i>n</i>=193, 39.3) (95% CI: 36.0-NR) and medium (<i>n</i>=62, 21.2) (95% CI: 16.6-25.6). <b>Conclusions:</b> This nomogram uses baseline characteristics to improve the prediction of PFS in patients undergoing maintenance therapy with either olaparib-bevacizumab or bevacizumab after first-line chemotherapy. The nomogram will be useful in designing and stratification of patients in future clinical trials.

AGO-OVAR 28/ENGOT-ov57: Niraparib versus niraparib in combination with bevacizumab in patients with carboplatin-taxane based chemotherapy in advanced ovarian cancer—A multicenter, randomized, phase III trial.

TPS5612 Background: Standard of care chemotherapy in patients (pts) with advanced ovarian cancer (AOC) is the combination of carboplatin and paclitaxel. Data from the PRIMA trial has shown a significant benefit in pts by the addition of a maintenance treatment (MT) with niraparib irrespective of BRCA or HRD-status in high-grade ovarian cancers (OC). The PAOLA-1 trial evaluated MT in pts with AOC with the combination of olaparib and bevacizumab and has also shown a significant benefit compared to bevacizumab monotherapy. However, it is unclear if a PARP-inhibitor (PARPi) MT monotherapy is sufficient or if the addition of bevacizumab is needed. Therefore, we investigate, if the treatment strategy of carboplatin / paclitaxel / bevacizumab / PARPi is superior to the treatment of carboplatin / paclitaxel / PARPi in an all-comer population. Methods: AGO-OVAR 28/ ENGOT-ov57 (NCT05009082; EudraCT Number: 2021-001271-16) is an Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Study Group led, international, multicenter, randomized, prospective phase III trial within the ENGOT trial network. The trial population is composed of adult pts with newly diagnosed, advanced high-grade epithelial OC, primary peritoneal cancer or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). All pts should have completed the first cycle of chemotherapy (carboplatin and paclitaxel) as part of Study Run-In-Period. Prior to day1 of cycle2, pts with a valid central tumor BRCA ( tBRCA) test result will be randomized 1:1 into either Arm1 and will receive 5 additional cycles of carboplatin and paclitaxel, q21d followed by niraparib for up to 3 years; or into Arm2 where pts will receive 5 additional cycles of carboplatin and paclitaxel plus bevacizumab, q21d followed by bevacizumab, q21d (for up to 1 year) and niraparib for up to 3 years. Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery are also allowed to be included in the trial. The primary objective is progression free survival (PFS). Secondary objectives include but are not limited to: PFS according to tBRCA-status, overall survival, PFS2, safety and tolerability, and quality of life. The trial will start in Q1/2022 with First Patient First Visit expected in Q2/2022. It is planned to recruit 970 patients. Clinical trial information: NCT05009082.

Interval debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer - retrospective study comparing surgery after 3 cycles or more of chemotherapy

ObjectiveTo evaluate and compare overall survival and progression-free survival in two groups of patients with advanced ovarian cancer, managed by neoadjuvant chemotherapy (3 cycles or more) followed by interval debulking surgery. Secondary objectives regarded surgical morbidity and extent of cytoreduction. Material and MethodsWe conducted a retrospective study, in a referral center, evaluating the management of patients diagnosed with advanced ovarian cancer (FIGO IIIC-IV) beneficiating of interval surgery after neoadjuvant chemotherapy. We compared two groups, one in which patients underwent 3 cycles of chemotherapy before surgery, and a second group in which patients underwent more than 3 cycles. Results140 patients underwent interval surgery after neoadjuvant chemotherapy. Among these patients, 45 patients underwent 3 or less cycles (group 1) and 95 patients more than 3 cycles (group 2). There was no statistical difference for overall and progression free survival. The mean overall survival was 58,4 months for group 1 and 58,3 for group 2 (p.value = 0.56). The mean progression free survival was 30,5 months for group 1 and 23,8 months for group 2 (p.value = 0.17). More posterior pelvectomies were realized in group 1 compared to group 2 with a statistically significant difference (p=0,01). There was no difference regarding complete macroscopic difference during the surgery between the 2 groups (p=0,09). ConclusionDebulking surgery is an invasive and heavy procedure and is not always possible in first line. Neoadjuvant chemotherapy followed by interval debulking surgery is an accepted alternative. The number of administered cycles is questionable, and does not seem to have a significant impact on overall survival and progression free survival. However, surgical morbidity is significantly reduced by increased cycles of chemotherapy.

Current trends in chemotherapy for advanced ovarian cancer.

Chemotherapy for advanced ovarian cancer has progressed over the past several decades with the introduction of cytotoxic agents. Various methods, including single agents, combination therapy and changes in the method of administration, have been validated in many clinical trials and have been combined in an attempt to improve the prognosis of advanced ovarian cancer. In recent years, molecular-targeted agents have been added to cytotoxic agents as a treatment option for maintenance therapy; however, their efficacy has been limited, and further development of treatment options is expected. The advent of poly(ADP-ribose) polymerase inhibitors has considerably improved prognosis and has affected treatment strategies for advanced ovarian cancer over the past few years. With the addition of the recently introduced immune checkpoint inhibitors, future treatment strategies for advanced ovarian cancer may become more complex. In this review, we introduce the latest advances in chemotherapy for advanced ovarian cancer and discuss future perspectives.

The importance of the Peritoneal Cancer Index (PCI) to predict surgical outcome after neoadjuvant chemotherapy in advanced ovarian cancer

PurposeAchieving complete cytoreduction (CCR) is crucial for a patient’s prognosis with advanced epithelial ovarian cancer (EOC). So far, prognostic predictors have failed to predict surgical outcome after neoadjuvant chemotherapy (NACT). In clinical trials, scores were used to predict operability in recurrent ovarian cancer (Harter et al. in N Engl J Med 385(23):2123–2131, 2021) but there is no known prediction score for CCR after NACT. The Peritoneal Cancer Index (PCI) is an established tool to predict surgical outcome in primary setting (Lampe et al. in 25:135–144, 2015). We now examined the predictive power of the PCI to achieve CCR after NACT.MethodsIn this single-center study, the data of patients with advanced stage EOC (FIGO > IIIb) treated between 01/2015 and 12/2020 were analyzed retrospectively. Inclusion criteria were a mandatory staging laparoscopy, a PCI score > 25, and NACT. CT scans were analyzed in blinded fashion according to RECIST criteria (Borgani et al. in 237; 93–99, 2019) Reaction of PCI after NACT was compared with the analysis of radiologic imaging and CA-125 levels.ResultsThree hundred and sixteen patients were screened, 62 were treated with NACT, and 23 were included in our analysis. 87% of cases presented with an FIGO IIIc stadium. The reduction of PCI itself after NACT showed to be the most powerful predictor for achieving CCR. The reduction of the initial PCI score by minimum of 8.5 points was a better predictor for CCR than reaching a PCI < 25. In contrast to data deriving from patients undergoing primary debulking surgery (PDS), we found a PCI of 17, rather than 25, to be a more valuable cut-off for CCR in neoadjuvant-treated patients.ConclusionThe extend of PCI reduction after NACT is a better predictor for achieving CCR compared with CA125 levels and radiologic imaging. The PCI must be assessed differently in neoadjuvant setting than in a primary situation. CCR was most likely for a post-NACT PCI < 17.

Effect of Bevacizumab Combined with Neoadjuvant Chemotherapy in Advanced Ovarian Cancer and the Occurrence of Adverse Reactions

Objective: To explore the effect of bevacizumab combined with neoadjuvant chemotherapy in advanced ovarian cancer and the occurrence of adverse reactions. Methods: A total of 80 patients with advanced ovarian cancer, treated in Affiliated People’s Hospital of Inner Mongolia Medical University from June 2019 to December 2020, were randomly divided into two groups. In the chemotherapy group, 40 patients were treated with neoadjuvant chemotherapy, while in the combined group, another 40 patients were treated with bevacizumab combined with neoadjuvant chemotherapy. The therapeutic effects were compared at the end of the treatment cycle. Results: There was no significant difference in the levels of CA125, CEA, and VEGF between the two groups before treatment. However, after the treatment cycle, the levels of CA125, CEA, and VEGF in the combined group were significantly better than those in the chemotherapy group (P &lt; 0.05). At the same time, the incidence of adverse reactions of the chemotherapy group was 67.50%, which was significantly higher than that of the combined group (35.00%; P &lt; 0.05). Conclusion: Bevacizumab combined with neoadjuvant chemotherapy for patients with advanced ovarian cancer has significant curative effect. The combined therapy reduces the levels of tumor markers and inflammatory factors, improves patients’ quality of life, as well as reduces adverse reactions. It has high clinical promotion value.

Multiple genetic variants predict the progression-free survival of bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study.

Bevacizumab (BV) plus chemotherapy is broadly used in advanced ovarian cancer (OC). However, the efficacy of BV-based regimens for advanced OC patients is not satisfactory. Therefore, it is urgent to explore the predictive genetic biomarkers for BV.Tumor tissues from advanced OC patients receiving BV-based regimens were analyzed with a 150-gene targeted panel for next generation sequencing. The associations between gene alterations or clinicopathology features and progression-free survival (PFS) were analyzed by Kaplan–Meier curves or Cox regression. The association of the genetic alteration in potential predictive genes and expressions of 11 vascular endothelial growth factor-related genes were analyzed in The Cancer Genome Atlas cohort using 292 OC cases.Sixty two Chinese advanced OC patients treated with BV-based therapy were included. The median PFS of was 6.9 months, and objective response rate was 14.5%. In multivariate Cox regression analysis, the status of endothelial growth factor receptor (EGFR) (hazard ratio = 6.39, 95% confidence interval [CI] 2.25–18.13, P < .001) and human epidermal growth factor receptor 2 (HER2) (hazard ratio = 3.58, 95% CI 1.27–10.08, P = .016) were significantly correlated with PFS. MYC Proto-Oncogene amplification seemed to have a positive trend (hazard ratio = 0.21, 95% CI 0.05–1.02, P = .052). Moreover, EGFR and HER2 alterations were not prognostic factors of overall survival for OC in The Cancer Genome Atlas OC cohort. The vascular endothelial growth factor-related signature analysis indicated vascular endothelial factor A expression was upregulated with EGFR alterations (P = .034) which may be involved in BV resistance, and HER2 alterations were associated with hypoxia inducible factor 1 subunit alpha overexpression significantly (P = .029).EGFR or HER2 alterations are negative predictors of PFS for OC patient treated with BV plus chemotherapy. Therefore, the clinicians may consider to use alternative regimens such as anti-EGFR or anti-HER2 targeted therapy instead of BV-based regimens on these patients when standard care fail.

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy at primary cytoreduction of epithelial ovarian cancer based on residual disease status

<h3>Objectives:</h3> Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to confer an overall survival (OS) benefit in a cost-effective manner when used at interval cytoreductive surgery after neoadjuvant chemotherapy for advanced ovarian cancer. Regarding the use of HIPEC at primary cytoreductive surgery (PCS), a recent multicenter retrospective cohort study demonstrated an OS advantage compared to PCS alone in women with stage III epithelial ovarian cancer (EOC). The objective of this study was to evaluate the cost-effectiveness of HIPEC in this setting. <h3>Methods:</h3> A decision analytic cost-effectiveness model of the US health care sector using simulated patients with stage III primary epithelial ovarian cancer was developed for three scenarios: 1) patients with optimal cytoreduction, 2) patients with suboptimal cytoreduction, and 3) all patients regardless of residual disease status. The base case for each model compared two surgical strategies: 1) PCS versus 2) PCS with HIPEC. Model inputs including median survival time, Kaplan-Meier estimates of OS, and costs were obtained from published studies. The time horizon was three years. The primary outcome was incremental cost-effectiveness ratio (ICER) in US dollars per life-year saved (LYS). <h3>Results:</h3> Assuming a willingness-to-pay threshold of $100,000 per LYS, PCS with HIPEC could be considered cost-effective in all three scenarios compared with PCS alone. The ICER was $9,789/LYS in optimally cytoreduced patients, $18,164/LYS in suboptimally cytoreduced patients, and $7,854/LYS for all patients regardless of residual disease burden. <h3>Conclusions:</h3> PCS with HIPEC appears to be a cost-effective strategy for patients with advanced epithelial cancer with all ICERs far below the willingness-to-pay threshold. This warrants further investigation of HIPEC in these clinical settings.

Partial response or stable disease after neoadjuvant chemotherapy for advanced ovarian cancer: time for surgery or more chemotherapy?

<h3>Objectives:</h3> The association between number of neoadjuvant chemotherapy (NACT) cycles prior to interval tumor reductive surgery (iTRS) and survival is poorly defined. The question of whether to proceed with surgery or more chemotherapy in a patient who does not have a complete response after 3-4 cycles of NACT remains unanswered. We sought to assess survival outcomes stratified by number of chemotherapy cycles and residual disease following iTRS in a population of patients with partial response (PR) or stable disease (SD) following 3-4 cycles of NACT. <h3>Methods:</h3> We identified a retrospective cohort of patients diagnosed between 2/2013 and 2/2018 who received at least 3 cycles of NACT (based on laparoscopic triage and/or medical and disease criteria) underwent iTRS for advanced ovarian cancer. All patients had a PR or SD following 3-4 NACT cycles based on imaging and CA-125. The population was divided into 4 groups based on number of NACT cycles prior to iTRS and residual disease status after iTRS (R0, no gross residual or R1, any amount of residual disease): (1) 3-4 NACT cycles/R0; (2) 3-4 NACT cycles/R1; (3) >4 cycles/R0; (4) >4 cycles/R1. Overall-survival (OS) and progression-free survival (PFS) were estimated using Kaplan and Meier product-limit estimator and modeled via the Cox proportional-hazards model. <h3>Results:</h3> The cohort consisted of 279 patients with a median age of 64. Most of the cohort was White (86.9%) with high-grade serous histology (90.3%) and stage IV disease (56.0%). The majority of patients received 3-4 cycles (73.8%), had a PR to NACT (92.8% vs 7.2% SD), with an overall R0 rate of 79.3%. For the entire cohort, R0 status was associated with improved OS (median of 43 months vs. 26 months; p<0.001). Receipt of > 4 cycles with an R0 resection was not associated with worse OS (HR 1.22, 95% CI 0.76-1.95) when compared to those who received 3-4 cycles with an R0 resection after iTRS. In the presence of R1 resection, receipt of 3-4 cycles or >4 cycles was associated with decreased OS (HR 1.89, 95% CI 1.17-3.05; HR 3.00 95% CI 1.65-5.46 respectively) compared to 3-4 cycles with a R0 resection. Only receipt of >4 NACT cycles with a R1 resection was statistically associated with worse PFS (HR 2.21 95% CI 1.38-3.55) compared to receipt of 3-4 cycles with a R0 resection. <h3>Conclusions:</h3> Residual disease is significantly associated with OS regardless of number of NACT cycles in patients with PR or SD to NACT. These data suggest that the ability to achieve R0 should take precedence in decision making regarding timing of surgery in patients who do not have a complete response to NACT for advanced ovarian cancer and that surgery can still benefit patients who require additional chemotherapy in order to be considered resectable.

Multimodal Treatment of Primary Advanced Ovarian Cancer.

Epithelial ovarian cancer is the second most common malignancy of the female genital tract, with approximately 7,400 new cases annually in Germany. With 5,500 deaths per year, ovarian cancer is the leading gynecologic cause of death. Epithelial ovarian cancer is characterized by morphologic heterogeneity with 4 molecular biological subtypes (immunoreactive-like, differentiated-like, proliferative-like, mesenchymal-like) with different prognosis. Significantly improved survival is achieved by optimal debulking with no residual disease (R0). Systematic lymphonodectomy of clinical negative lymph nodes has no effect on overall survival in advanced ovarian cancer. Interval debulking in advanced ovarian cancer after three cycles of neoadjuvant chemotherapy with carboplatin/paclitaxel is controversial. Standard chemotherapy for advanced ovarian cancer consists of six cycles of carboplatin AUC5 and paclitaxel 175 mg/m2, in a three-week cycle. Intraperitoneal chemotherapy is not a standard therapy. Anti-hormonal therapy with an aromatase inhibitor plays a minor role in therapy of both low grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC). A major achievement in ovarian cancer therapy has been the results of the SOLO-1 trial, in which olaparib as a first line maintenance monotherapy resulted in an overall 70% lower risk of disease progression in patients with advanced Breast Cancer Gene (BRCA)-mutated ovarian cancer.

Venous Thromboembolism in Patients Receiving Neoadjuvant Chemotherapy for Advanced Ovarian Cancer and Impact on Survival.

To determine the incidence of venous thromboembolism (VTE) in patients with ovarian cancer receiving neoadjuvant chemotherapy (NACT), identify risk factors for VTE, and assess the effect of VTE on treatment trajectory and overall survival. This is a retrospective cohort study of patients diagnosed with ovarian, fallopian tube, or primary peritoneal cancer treated with NACT between 2013 to 2016 in Alberta, Canada. The primary outcome was incidence of VTE during NACT. Secondary outcomes were risk factors for VTE and overall survival. Data related to patient demographics, cancer treatment, and incidence of VTE were collected. Statistical analyses included Kaplan-Meier estimates and univariate and multivariate Cox regression analysis. A total of 284 patients were included in this study. Average age at diagnosis was 63.8 years. The incidence of VTE during NACT was 13.3%. Patients with VTE were less likely to undergo interval debulking surgery (58.3%) than patients without VTE (78.6%). Kaplan-Meier estimates demonstrated a decrease in overall survival in patients who had VTE during NACT (15.0 mo; 95% CI 14.5-16.5) compared with patients who did not (26.8 mo; 95% CI 22.8-30.9) (P < 0.0001). Multivariate analysis identified albumin <35 g/L, BMI >30 kg/m2, and non-serous histology as risk factors for VTE. The risk of VTE in this cohort was 13.3%, which was associated with decreased overall survival. These findings suggest that thromboprophylaxis may have a role in this patient population.