Therapy Of Advanced Ovarian Cancer Research Articles

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer.

Olaparib (Lynparza®) is a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor approved for first-line maintenance treatment in adults with advanced ovarian cancer who are in complete or partial response to first-line, platinum-based chemotherapy. Originally approved as monotherapy, olaparib is also approved to be administered in combination with bevacizumab in patients whose cancer is associated with homologous recombination deficiency (HRD), defined by either a BRCA1/2 mutation and/or genomic instability. In phaseIII trials, olaparib monotherapy significantly improved progression-free survival (PFS) relative to placebo (SOLO-1), as did olaparib plus bevacizumab relative to placebo plus bevacizumab (PAOLA-1), in patients with advanced ovarian cancer who had responded to platinum-based chemotherapy. In PAOLA-1, improvements in PFS with olaparib plus bevacizumab were not seen in patients with HRD-negative tumours relative to placebo plus bevacizumab. Both olaparib monotherapy and olaparib in combination with bevacizumab had generally manageable tolerability profiles. Olaparib, alone or in combination with bevacizumab, is a useful option for the first-line maintenance treatment of adults with HRD-positive, advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy.

Budget impact analysis of niraparib for first-line maintenance therapy in advanced ovarian cancer from a US payer perspective.

BACKGROUND: Ovarian cancer (OC) is the fifth leading cause of cancer death in women and has the highest mortality rate of gynecological cancers. Niraparib was recently approved by the FDA for the maintenance treatment of adult patients with advanced epithelial OC in complete or partial response to first-line platinum-based chemotherapy (PBC) regardless of biomarker status. OBJECTIVE: To estimate the direct economic impact on US payers of adding niraparib as a first-line maintenance therapy for patients with advanced OC. METHODS: The model considered 2 scenarios: a current scenario in which niraparib does not have regulatory approval for first-line maintenance therapy and a future scenario in which niraparib has regulatory approval for first-line maintenance therapy. The budget impact was calculated as the difference in cost between the 2 scenarios. The budget impact model (BIM) considered 2 different US health care payer perspectives: a commercial health plan and a Medicare plan. Both payer perspectives were assumed to have a hypothetical 1 million affiliates that were covered. Epidemiological data was used to estimate the eligible incident population of patients with OC. Active surveillance, bevacizumab (as a monotherapy), and olaparib (as a monotherapy restricted to patients with the breast cancer gene [BRCA] mutation) were included in the model as alternative maintenance treatment options (maintenance treatment options required 1% market share for inclusion). Cost categories considered in the BIM included diagnostic testing, treatment acquisition and administration, treatment-emergent adverse events, and subsequent therapy. Results were presented as an incremental budget impact to payers over 3 years. RESULTS: For a commercial health plan of 1 million affiliates, the estimated impact of adding niraparib as a first-line maintenance treatment option for advanced epithelial OC was calculated as $87,906, $93,106, and $87,037 for years 1, 2, and 3, respectively. The average budget impact per member per month was $0.007. For a Medicare health plan of 1 million affiliates, the estimated impact was calculated as $206,785, $219,017, and $204,739 for years 1, 2, and 3, respectively. The average budget impact per member per month was $0.018. One-way sensitivity analyses suggested that budget impact was most sensitive to the treatment duration and market share of niraparib, the non-treatment-specific data on overall survival rates, and the treatment duration of bevacizumab. Treatment of drug-specific adverse events had little impact on the budget model. CONCLUSIONS: The model estimated a minimal budget impact to both a commercial or Medicare health plan following the introduction of niraparib as a first-line maintenance therapy for patients with advanced epithelial OC who are in complete or partial response to first-line PBC regardless of biomarker status. DISCLOSURES: This study was financially supported by GlaxoSmithKline. Liu, Hawkes, Maiese, and Hurteau are employees of GlaxoSmithKline. Travers was employed by GlaxoSmithKline at the time of this study. Spalding and Walder are employees of FIECON Ltd., which was contracted by GlaxoSmithKline to develop the budget impact model used in this study.

Clinical outcomes and cost associated with HRD biomarker guided first line maintenance therapy in advanced ovarian cancer

<h3>Objectives:</h3> Olaparib is approved as a first line (1L) maintenance (mtx) option, as monotherapy for <i>BRCA</i> mutated (BRCAm) ovarian cancer (OC) and in combination with bevacizumab (Bev) for homologous recombination deficient (HRD) OC. Niraparib monotherapy is approved as 1L mtx irrespective of BRCA/HRD status. Despite its broad approval, niraparib demonstrated relatively shorter progression free survival (PFS) gains outside of an HRD test positive population in the PRIMA trial. Given the recent PARPi data in frontline mtx and the cost of HRD testing beyond standard of care g<i>BRCA</i> testing, there is debate over using an HRD biomarker guided (BMG) or non-biomarker guided (NBMG) approach to prescribing 1L mtx. The objective of this model is to compare the PFS and costs per month of PFS between: (1) BMG 1L mtx approach which restricts the prescribing of 1L mtx PARPi and PARPi combination based on Myriad myChoice results vs (2) NBMG PARPi mtx for all approach. <h3>Methods:</h3> This model is a parametric Markov model for a cohort of 100 newly diagnosed stage 3/4 OC patients (pts) prescribed 1L mtx according to HRD BMG and NBMG approaches. The model focuses on maintenance after first line treatment and evaluates costs and PFS after first line chemotherapy. To focus on the impact of testing, drugs are treated as classes. Treatment costs include 1L mtx PARP inhibitor (PARPi), Bev, and PARPi + Bev, subsequent therapy, management of adverse events, and administration costs over 60 months. PFS is estimated by applying an exponential curve to adjusted trial data. The BMG pt group undergoes HRD tumor testing and has a test positive (HRD+) rate of 47% (20% BRCAm, 27% non-BRCAm). Germline <i>BRCA</i>m testing cost is not included as it is assumed to be the standard of care and equally conducted in both groups. An estimated 65% are eligible for a PARPi (received and responded to 1L platinum chemotherapy). Calculations for the BMG PARPi eligible group assume all HRD+ pts receive PARPi + Bev and 30% of HRD test negative pts receive Bev (70% receive routine surveillance). The model assumes all pts in the NBMG group receive a PARPi. <h3>Results:</h3> In the BMG group 31 pts receive PARPi + Bev mtx and in the NBMG arm 65 pts receive PARPi mtx. The 31 BMG PARPi + Bev pts averaged 36.6 months of 1L PFS compared to 26.3 months in the 65 NBMG PARPi pts. The overall 1L PFS for the total cohorts were similar but slightly favored the BMG approach (1715.4 vs 1711.7 months). Over a 60 month horizon, the BMG approach was $1,002 less per month of 1L PFS gained ($15,475 vs. $16,477). HRD biomarker testing represented 1.5% of the total costs for the cohort. <h3>Conclusions:</h3> Despite initial testing costs, this model projects that use of an HRD BMG approach with PARPi + bev may minimize long-term costs and afford at least similar, if not greater, 1L PFS compared to an approach which omits HRD tumor testing and prescribes PARPi to all-comers.

Phase II OVARIO Study of niraparib + bevacizumab therapy in advanced ovarian cancer following front-line platinum-based chemotherapy with bevacizumab

<h3>Objectives:</h3> Niraparib improves progression-free survival (PFS) in newly diagnosed, recurrent, and heavily pretreated ovarian cancer (OC) in patients (pts) after platinum-based chemotherapy in all biomarker-defined subgroups. Bevacizumab-induced hypoxia can drive genomic instability by altering DNA damage repair pathways, including homologous recombination (HR), and it is hypothesized to sensitize tumors to poly(ADP-ribose) polymerase inhibition. OVARIO (NCT03326193) is a single-arm, open-label study evaluating niraparib + bevacizumab treatment in advanced OC after response to first-line (1L) platinum-based chemotherapy + bevacizumab. <h3>Methods:</h3> All pts with newly diagnosed high-grade serous or endometrioid stage IIIB-IV OC who had a complete response (CR), partial response, or no evidence of disease (NED) after 1L platinum-based chemotherapy + bevacizumab were eligible. Pts receiving neoadjuvant chemotherapy (NACT) or primary debulking surgery were eligible. All pts underwent tissue testing for HR deficiency (HRd) or proficiency (HRp) at enrollment. Bevacizumab dosage was 15 mg/kg q3w up to 22 cycles, including time on 1L chemotherapy. Niraparib, 300 or 200 mg qd, based on baseline body weight and platelet count, was started within 12 weeks of completing 1L treatment and continued for 3 years or until progressive disease or unacceptable toxicity. The primary endpoint was PFS rate at 18 months from treatment initiation of niraparib + bevacizumab maintenance. <h3>Results:</h3> The study completed enrollment at 105 pts. Most pts were stage III (79%), had serous histology (95%), received NACT (63%), and had CR/NED at the completion of 1L (63%). Overall, 47% of pts were HRd, including HRd<i>-BRCA</i> mutated and HRd<i>-BRCA</i> wild-type. The niraparib starting dose was 200 mg in 78% of pts. At 6 and 12 months, PFS rates were 90% and 75%, respectively. At 12 months, the most common grade ≥3 related treatment-emergent adverse events were thrombocytopenia, anemia, and hypertension (49% of pts had pre-existing hypertension). Further safety data and PFS rates at 18 months will be presented at the meeting. <h3>Conclusions:</h3> Safety of the niraparib + bevacizumab combination was consistent with the known side effects of each drug as monotherapy, and the preliminary data suggest that the combination is efficacious. <h3>ClinicalTrials.gov number:</h3> NCT03326193

PARP inhibitors and immunotherapy in ovarian and endometrial cancers.

Advanced ovarian and endometrial cancers have historically been associated with poor prognosis and few treatment options, limited to single or doublet chemotherapy regimens. The introduction of novel target therapies has transformed the management of these cancers. In contrast to chemotherapy, which inhibits DNA replication and mitosis, targeted therapies target cancer signalling pathways, stroma, immune-microenvironment and vasculature in tumour tissues. The most notable advances in gynaecological cancers have come from the introduction of PARP inhibitors and immune checkpoint inhibitors for ovarian and endometrial cancer, respectively. Several PARP inhibitors, which target defective DNA repair, have been approved as maintenance therapy for advanced ovarian cancer in both the first line and platinum-sensitive relapsed settings. Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have proven successful in advanced mismatch repair deficient endometrial cancers with use now being investigated beyond this population. This review will explore the biological rationale and clinical evidence behind the use of PARP inhibitors and immunotherapy in ovarian and endometrial cancers.

Expectations and Challenges of First-Line Maintenance Therapy for Advanced Ovarian Cancer.

The incidence of ovarian cancer, which has had a poor prognosis, is increasing annually. Currently, the prognosis is expected to improve with the use of molecular-targeted drugs and immune checkpoint inhibitors as maintenance therapies after the first-line chemotherapy. The GOG218 and ICON7 studies reported the usefulness of bevacizumab and the SOLO-1 and PRIMA (A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy) studies have reported the usefulness of olaparib and niraparib, respectively. The ATHENA study investigating the usefulness of rucaparib is currently ongoing. Although clinical studies of immune checkpoint inhibitors are lagging in the field of gynecology, many clinical studies using programmed death cell-1 (PD-1) and PD-1 ligand 1 (PD-L1) antibodies are currently ongoing. Some biomarkers have been identified for molecular-targeted drugs, but none have been identified for immune checkpoint inhibitors, which is a challenge that should be addressed in the future.

Narrative review of cytoreductive surgery and intraperitoneal chemotherapy for peritoneal metastases in ovarian cancer.

Due to numerous factors, such as no specific symptoms and ineffective screening to identify premalignant or early-stage disease, most patients with ovarian cancer present with advanced-stage disease and overt peritoneal metastases. Currently, the most effective treatment for these patients is complete cytoreductive surgery with systemic platinum/taxane-based chemotherapy. Over the past few decades, many researchers have evaluated the use of postoperative normothermic intraperitoneal (NIPEC) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) delivery as additional treatment modalities. Here, we will review the current status and future directions for these treatment strategies in the management of ovarian cancer. Most of the studies in this area of research have been retrospective in nature, limited by heterogeneous patient populations and large variance in chemotherapeutic regimens used, leading to mixed results and difficulties in evaluating the clinical impact of the data. More mature data from prospective trials are lacking, and IP therapy for advanced ovarian cancer should still be considered an investigational approach and evaluated only in clinical trials; the exception is for patients with stage III disease who undergo interval debulking surgery after neoadjuvant chemotherapy, for whom HIPEC can be considered in selected patients as part of first-line therapy.

The latest first-line treatment options for ovarian cancer: focus on maintenance therapy

Ovarian cancer is one of the leading causes of death from gynecologic cancers in Russia: in 2018, 7616 women died from this disease and the proportion of patients who is under observation for 5 years or more was only 3.4%, which probably indicates very low 5-year survival. At the same time, there was is a tremendous paradigm shift in the treatment of BRCA-associated ovarian cancer. A number of large phase III trials have been published on the use of PARP inhibitors in this subtype of the disease. Their results demonstrated a marked reduction in the risk of disease progression or death with PARP inhibitors after first-line therapy for advanced ovarian cancer. Here we present a comparative analysis of the efficacy of various PARP inhibitors in BRCA-associated ovarian cancer. The relative risk reduction in disease progression or death for olaparib, niraparib and veliparib was 70%, 60% and 56%, respectively and advantage of using these drugs noted in all patient subgroups. Comparative analysis of the safety of various PARP inhibitors was carried out as well, the risks of developing various toxicity were assessed. Based on a comparison of published data on their safety profile, it was concluded that olaparib is the safest drug of this class, especially in the context of therapy on an outpatient basis. Possible ways to optimize the use of PARP inhibitors in disseminated ovarian cancer have been analyzed.

Phase II OVARIO study of niraparib + bevacizumab therapy in advanced ovarian cancer following front-line platinum-based chemotherapy with bevacizumab

Objective: Niraparib improves progression-free survival (PFS) in newly diagnosed and recurrent ovarian cancer (OC) in patients after platinum-based chemotherapy in all biomarker-defined subgroups. OVARIO (NCT03326193) is a single-arm study evaluating niraparib + bevacizumab treatment in advanced OC after response to first-line platinum-based chemotherapy + bevacizumab.

Weekly Carboplatin and Paclitaxel: A Retrospective Comparison with the Three-Weekly Schedule in First-Line Treatment of Ovarian Cancer.

Conventional first-line combination therapy for ovarian cancer comprises 6 cycles of adjuvant or neoadjuvant carboplatin (AUC5-6) with paclitaxel (175 mg/m2 ) every 3 weeks (PC-3W). Weekly scheduling of paclitaxel may maximize its antiangiogenic effect and reduce adverse effects. We compared the efficacy and safety of PC-3W with a modified protocol of weekly paclitaxel 80 mg/m2 and weekly carboplatin AUC2 administered on days 1, 8, and 15 in a 28-day cycle (i.e., with 1 week off-treatment [PC-W]). Medical records of consecutive patients treated between 2000 and 2018 were reviewed; 707 patients were analyzed for demographic and clinical characteristics, effectiveness and toxicity. PC-3W was administered to 402 patients (median age, 60.5 years) and PC-W to 305 patients (median age, 62.5 years). Most patients (91.4%) were diagnosed at stage III-IV. Notwithstanding a higher proportion of residual disease and older patients in the PC-W group, median progression-free survival was 21.4 months and 13.2 months for PC-W and PC-3W, respectively; median overall survival was 75.2 and 54.0 months for PC-W and PC-3W, respectively. Cox proportional hazards model indicated improved survival for patients treated with PC-W (hazard ratio, 0.54). Similar results were observed for older patients diagnosed at ≥75 years. PC-W demonstrated a better safety profile, with lower incidence of neuropathy, neutropenia, and alopecia. PC-W is as active and better tolerated than the standard PC-3W regimen. PC-W may serve as an alternative option for elderly or frail patients. Weekly scheduling of paclitaxel 80 mg/m2 and carboplatin AUC2, administered on days 1, 8, and 15 in a 28-day cycle (PC-W) for first-line therapy for advanced ovarian cancer, is as active and better tolerated than the standard regimen of carboplatin and paclitaxel (175 mg/m2 ) every 3 weeks (PC-3W). It is possible that the weekly holiday on day 21 in the PC-W regimen may ensure better completion rates (which may result in treatment delays for toxicity in PC-3W). The results of this retrospective analysis highlight the weekly regimen as a valid treatment option, especially for elderly patients and those with significant comorbidities.

Is it possible to improve primary therapy of advanced ovarian cancer?

In 2011, a standard approach to the treatment of primary ovarian cancer (OC) included a cytoreductive surgery, which could be performed after 2–3 cycles of neoadjuvant chemotherapy, and chemotherapy consisting of platinum and taxanes. Such approach was provided for all patients, regardless of tumour histology and any molecular biological and genetic factors. The most complete picture of management and therapy of patients can be made using the treatment of a specific patient as an example. After application to the N.N. Blokhin National Medical Research Center of Oncology in 2011, the patient with OC received standard primary therapy and subsequent treatment of the recurrent disease, which was accompanied by various types of adverse events resulting in the poor quality of life for the patient. The data that some patients with OC have a BRCA1/2 mutation that is significant for prognosis and treatment came to hand later and, unfortunately, the awareness of a significant germinal BRCA1 mutation was of no use to the woman any longer. The life expectancy of this patient was 47 months. This is the average life expectancy for patients with stage IIIC OC. Major changes have been brought in the primary therapy of OC. If a diagnosis of low-grade IIIC ovarian adenocarcinoma was established in this patient today, needless to say that the BRCA1 mutation would be identified during the first-line chemotherapy, and in case of full or partial treatment effect, we would prescribe olaparib as maintenance therapy to the patient. Considering the fact that the median progression-free survival has not yet been achieved in the patients of SOLO-1 study, who received olaparib therapy, and is only approaching 54 months, it can be assumed that even the first relapse could not have developed in this patient.

Total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation): a novel surgical technique for advanced ovarian cancer

BackgroundA Total Retroperitoneal en bloc resection Of Multivisceral-Peritoneal packet (TROMP operation) is a no-touch isolation technique in a retroperitoneal space to resect the parietal peritoneum and the affected organs in...

Intensive Intraperitoneal Therapy in Advanced Ovarian Cancer

Intensive Intraperitoneal Therapy in Advanced Ovarian Cancer

Clinical benefit of hormonal therapy in advanced ovarian cancer

Objectives: To evaluate the benefit of hormonal therapy in advanced ovarian carcinoma. Materials and Methods: The present authors reviewed the data of advanced epithelial ovarian cancer patients who underwent hormonal therapy between 2009 and 2016. Primary endpoint was clinical benefit. Secondary endpoints were overall response rate, CA 125 response, overall survival, progression-free survival, and toxicity. Results: The authors identified 47 patients. Median age was 61 years. Serous carcinoma was the main histologic subtype (70%). Hormone receptor expression was positive in 23% of patients. Previous to hormonal therapy, 60% of patients were treated with two or more chemotherapy regimens (range 2-8). Hormonal therapy was initiated in 34% of patients due to disease progression and the remaining as maintenance therapy. No relevant toxicity was reported. Progression-free survival was six months (CI 95% 2.1-9.9) and overall survival was 22 months (CI 95% 13.0-31.0). Based on imaging response criteria, one patient had complete response, 70% had stable disease, and 19% progressed on the first evaluation. Overall clinical benefit was 72%. Discussion: Clinical benefit was superior to the reported in the literature, probably related to its maintenance use between chemotherapy treatments. More prospective studies are needed to determine the real advantage of hormonal therapy in advanced ovarian cancer vs. clinical surveillance, mainly in the maintenance setting, as well as its correlation with hormone receptor expression.

Total Retroperitoneal En Bloc Resection of Multivisceral-Peritoneal Packet (TROMP Operation): A Novel Surgical Technique for Advanced Ovarian Cancer; Retrospective Cohort Analysis of a Prospective Collected Database

Background: a total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation) is a no-touch isolation technique in a retroperitoneal space to resect the parietal peritoneum and the affected organs in advanced ovarian cancer. The study prescribed and analyzed the results of this novel technique for primary cytoreductive surgery. Methods: The study included 208 patients operated between January 2015 and December 2017 in Charite, Berlin. TROMP operation was performed in 58 patients, whereas the other 150 patients were operated with the conventional cytoreductive method. Findings: The complete tumor resection rate accounts for 87.9% in TROMP group and 61.3% in the conventional surgery group. (P=0.001). This difference was even stronger in the sub-group of very advanced stages (T3c+T4) (85.1% of TROMP group and in only 53.1% in the conventional surgery group, P=0.001). The duration of the primary cytoreductive surgery was about 33 minutes shorter in TROMP group (median: 335 minutes vs. 368 minutes; TROMP vs. conventional, respectively) in spite of the fact that the most advanced cytoreductive procedures were performed statically significant more in TROMP operation arm in comparison with the conventional surgery arm. There was no statistically significant difference between the groups regarding the postoperative complication, blood loss or the length of stay in intensive care unit. Interpretation: TROMP operation is a visible and very effective technique of surgical therapy in advanced ovarian cancer. This technique increased the complete tumor resection rate to 87.9% without increasing the blood loss, postoperative complications or the duration of surgery. A prospective randomized study is advised to validate these results. Funding Statement: The authors received no specific funding for this work. Declaration of Interests: 1. The first (MZM) author is an adviser for Stryker. He received in the last 2 yours honoraria from Olympus, Ethicon (Johnson and Johnson), Roche and Astrazeneca. 2. The second author (JS) received honoraria from Astrazeneca, Eisai, Clovis, Olympus, Johnsons and Johnson, PharmaMar, Pfizer, TEVA, TESARO, MSD and plays advisory roles by Astrazeneca, Clovis, Lilly, PharmaMar, Pfizer, Roche, TESARO, MSD. He received even research fundings (not for this study) from Astrazeneca, Clovis, Merck, Bayer, PharmaMar, Pfizer, TESARO, MSD. He discloses travel, accommodations, and other expenses paid or reimbursed by Astrazeneca, Clovis, PharmaMar, Roche, Pfizer, TESARO, MSD, and were parts of his scientific activities in the last 2 years. 3. The third author (AM) has no conflict of interest. 4. The fourth author (RR) has no conflict of interest. 5. The fifth author (JM) has no conflict of interest. Ethics Approval Statement: All patients provided their written informed consent before clinical data were collected. Approval from Charite local Ethics Committee was provided for this study (EK207/2003 Amendment 15/2012).

Success for First-Line PARP Inhibition in Ovarian Cancer

The use of PARP inhibitors as first-line maintenance therapy for advanced ovarian cancer improves progression-free survival, according to three phase III studies. The data also suggest that patients other than those with BRCA1/2 mutations may benefit from this class of drugs.

Olaparib in the therapy of advanced ovarian cancer: first real world experiences in safety and efficacy from China

PurposePoly (ADP-ribose) polymerase (PARP) inhibitor, is a milestone in treatment of ovarian cancer. However, there is no real world study from China regarding the clinical outcome of the taking PARP inhibitor (PARPi), Olaparib(Lynparza™). The goal of this research is to evaluate the side effects and short-term efficacy in advanced ovarian cancer patients who administered Olaparib.MethodsPatients with ovarian cancer, fallopian tube cancer and peritoneal cancer that treated with Olaparib in The Affiliated Cancer Hospital of Nanjing Medical University between September 2018 and June 2019 were recruited. The drug associated Adverse Events (AEs) were collected and short-term efficacy were analyzed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) .ResultsOf all 28 enrolled patients, 92.9% were ovarian cancer, 7.1% were fallopian tube cancer, and 39.3% cases harbored germline BRCA-mutation. There were 6(21.4%) patients received Olaparib after multi-line chemotherapy, and 10 patients (35.7%) as second-line maintenance therapy and 2 patients (7.1%) as first-line maintenance therapy. There were still other 10 cases (35.7%) received Olaparib as exploratory therapy. Abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling were newly reported AEs. Serious Adverse Events(SAEs) were usually managed by dose interruption or dose reduction, rather than discontinuation. 3 patients discontinued treatment, 8 patients received reduced dose of Olaparib, and 4 patients stopped therapy after the alleviation of AEs. Of all 28 enrolled cases, in monotherapy group, 1 of 6 patients achieved stable disease(SD) and also 2 patients achieved stable disease(SD) combined with anti-angiogenic drugs when disease progressed. 2 patients achieved complete remission(CR) and 3 patients were stable with exploratory therapy.ConclusionsThe AEs of Olaparib were all manageable. For the first time, we also identified several AEs such as abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling during the follow-up which have not been reported. The short-term efficacy was observed in some exploratory cases that provided new potential indication to PARPi-related clinical trials.

TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO‐OVAR OP7)

BackgroundPrimary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was...

Survival benefits of dose-dense early postoperative intraperitoneal chemotherapy in front-line therapy for advanced ovarian cancer: a randomised controlled study

Dose-dense early postoperative intraperitoneal chemotherapy (DD-EPIC) significantly increased non-progression rate in advanced ovarian cancer (OC) patients. We report final overall survival (OS) results to further strengthen the efficacy of DD-EPIC in the front-line therapy. In this phase 2 trial, 218 patients with FIGO IIIC–IV OC were randomly allocated to receive DD-EPIC followed by intravenous (IV) chemotherapy (DD-EPIC group), or IV chemotherapy alone (IV group). The study was prespecified to detect differences in progression-free survival (PFS) and OS. At a median follow-up period of 69.1 months, the median OS was 67.5 and 46.3 months in the DD-EPIC and IV group, respectively. The probability rate of OS at 5 years was 61.0% with DD-EPIC, and 38.2% with IV (hazard ratio [HR] for death from OC, 0.70; 95% confidence interval [CI], 0.49–1.00). DD-EPIC was associated with a prolonged PFS compared with the IV group (the estimated rate of PFS at 5 years, 26.0% vs. 8.5%; HR for disease progression, 0.64; 95% CI, 0.47–0.86). DD-EPIC was associated with a longer OS than IV chemotherapy alone. It may be considered as a valuable option of the front-line therapy for advanced ovarian cancer.Trial registration: ClinicalTrials.gov, NCT01669226 (date of registration: August 20, 2012).

Genomic-Based Therapy of Gynecologic Malignancies.

This paper will review the current status of genomic-based therapy of gynecologic malignancies. The routine "standard-of-care" delivery of targeted therapeutics based on the presence of specific molecular biomarkers in the management of the gynecologic malignancies has been delayed compared to the substantial progress made in several other tumor types. However, relatively recently reported and rather robust phase 3 trial data have confirmed a potentially major role for PARP inhibitors as both active treatment and maintenance therapy of advanced ovarian cancer. Further, data demonstrating the presence of a specific molecular phenotype (micro-satellite ( instability high - MSI-H) is a valid biomarker for the potential clinical utility of checkpoint inhibitor immunotherapy has relevance for all gynecologic malignancies, and particularly in the setting of metastatic or recurrent endometrial cancer. CONCLUSIONS: The introduction of PARP inhibitors into the oncology armamentarium has substantially impacted standard-of-care strategies in the management of ovarian cancer. It is anticipated that the results of ongoing and future trials will further define the role of genomic-based therapy in ovarian cancer and other gynecologic malignancies.