Mark Brady

• Roswell Park Comprehensive Cancer Center

PURPOSE We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC). PATIENTS AND METHODS NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometr...

Objectives: The primary objective of this analysis of GOG 252 is to assess the overall survival of the subgroup of participants with metastatic epithelial ovarian cancer, with no more than microscopic residual disease, following their primary cytoreductive surgery followed by three chemotherapy regimens and bevacizumab. The results of the response...

PURPOSE To compare taxane maintenance chemotherapy, paclitaxel (P) and paclitaxel poliglumex (PP), with surveillance (S) in women with ovarian, peritoneal, or fallopian tube (O/PC/FT) cancer who attained clinical complete response after first-line platinum-taxane therapy. METHODS Women diagnosed with O/PC/FT cancer who attained clinical complete r...

PURPOSE Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur. We assessed the activity of two all-oral nonplatinum alternatives, olaparib or olaparib/cediranib, versus platinum-based chemotherapy. PATIENTS AND METHODS NRG-GY004 is an open-label, randomized...

Background Age and ethnicity are among several factors that influence overall survival (OS) in ovarian cancer. The study objective was to determine whether ethnicity and age were of prognostic significance in women enrolled in a clinical trial evaluating the addition of bevacizumab to front-line therapy. Methods Women with advanced stage ovarian,...

Purpose Increasing measures of adiposity have been correlated with poor oncologic outcomes and a lack of response to anti-angiogenic therapies. Limited data exists on the impact of subcutaneous fat density (SFD) and visceral fat density (VFD) on oncologic outcomes. This ancillary analysis of GOG-218, evaluates whether imaging markers of adiposity w...

6077 Background: The phase III VELIA trial (NCT02470585) demonstrated statistically significant improvement in PFS per investigator (INV) for V added to CP and continued as maintenance (CPV-V) vs. CP alone in pts with newly diagnosed HGSC in the BRCA mutated ( BRCAm), homologous recombination deficient (HRD), and whole populations. Here we present...

6003 Background: Combination cediranib (C) and olaparib (O) improved progression-free survival (PFS) in patients (pts) with relapsed platinum (plat)-sensitive high-grade ovarian cancer (ovca) compared to O alone in a Phase 2 trial (NCT01116648). We conducted this randomized, open-label Phase 3 trial (NCT02446600) to assess whether combination C+O,...

(Abstracted from N Engl J Med 2019;381:1929–1939) The National Comprehensive Cancer Network recommends secondary cytoreduction for ovarian cancer patients with recurrent disease who have received no treatment for a period of 6 months following a complete response from prior chemotherapy. Retrospective reviews and meta-analyses have shown the most b...

Background: Secondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation. Methods: We randomly assigned patients with recurrent ovarian cancer who had received one previous therapy,...

Background This phase III randomized placebo (PL) controlled multinational trial evaluated whether progression-free survival (PFS) is increased when V is added to front-line carboplatin and paclitaxel (CP) and continued as maintenance in newly diagnosed HGSC pts considering BRCA mutations (m), homologous recombination deficiency (HRD), and neoadjuv...

Background: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. Methods: In an international, phase 3, placebo-controlled trial, we assessed the e...

(Abstracted from J Clin Oncol 2019;37:1380–1390) The Gynecologic Oncology Group (GOG) protocol 172 demonstrated a median survival of 127.6 months with an intraperitoneal (IP) chemotherapy regimen compared with 82 months with an intravenous (IV) cisplatin-based chemotherapy regimen in women with stage 3 ovarian cancer and surgically resected disease...

Objective: Adiposity has been hypothesized to interfere with the activity of bevacizumab (BEV), an anti-angiogenic agent. Measurements of adiposity, BMI, surface fat area (SFA), and visceral fat area (VFA) were investigated as prognostic of oncologic outcomes among patients treated with chemotherapy, with or without BEV, on GOG 218, a prospective...

Purpose: We report the final, protocol-specified analysis of overall survival (OS) in GOG-0218, a phase III, randomized trial of bevacizumab in women with newly diagnosed ovarian, fallopian tube, or primary peritoneal carcinoma. Methods: A total of 1,873 women with incompletely resected stage III to IV disease were randomly assigned 1:1:1 to six...

Purpose: To evaluate the impact of two different intraperitoneal (IP) chemotherapy regimens on progression-free survival (PFS) among women with newly diagnosed advanced ovarian carcinoma. Methods: Eligible patients were randomly assigned to six cycles of IV paclitaxel 80 mg/m2 once per week with intravenous (IV) carboplatin area under the curve...

In the era of personalized medicine, the introduction of translational studies in clinical trials has substantially increased their costs, but provides the possibility of improving the productivity of trials with a better selection of recruited patients. With the overall goal of creating a roadmap to improve translational design for future gynecolo...

Purpose: We hypothesized that mutations in homologous recombination repair (HRR) genes beyond BRCA1 and BRCA2 improve outcomes for ovarian carcinoma (OC) patients treated with platinum therapy and would impact the relative benefit of adding prolonged bevacizumab. Experimental Design: We sequenced DNA from blood and/or neoplasm from 1,195 women enr...

Background: On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified...

Background: Combining bevacizumab with frontline chemotherapy statistically significantly improved progression-free survival (PFS) but not overall survival (OS) in the phase III GOG-0218 trial. Evaluation of candidate biomarkers was an exploratory objective. Methods: Patients with stage III (incompletely resected) or IV ovarian cancer were rando...

Background: Platinum-based chemotherapy doublets are a standard of care for women with ovarian cancer recurring 6 months after completion of initial therapy. In this study, we aimed to explore the roles of secondary surgical cytoreduction and bevacizumab in this population, and report the results of the bevacizumab component here. Methods: The m...

Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces imm...

Background: A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would p...

Importance: Somatic mosaic mutations in PPM1D have been reported in patients with breast cancer, lung cancer, and ovarian cancer (OC), but cause or effect has not been established. Observations: To test the hypothesis that somatic mosaic mutations are associated with chemotherapy exposure, we used massively parallel sequencing to quantitate muta...

s: AACR Special Conference: Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; October 17-20, 2015; Orlando, FL Objective: Bevacizumab is an anti-vascular endothelial growth factor monoclonal antibody with activity in ovarian cancer. GOG 218 was a phase III, randomized trial in advanced primary ovarian, fallopian tube, and peritoneal...

Purpose: Somatic mosaic mutation in the PPM1D gene have been associated with risk of breast and ovarian cancer. Somatic mosaic mutations in blood cells may be associated with older age and chemotherapy exposure. We wanted to determine if somatic mosaic mutations in PPM1D and in other genes are associated with older age and repeated exposure to chem...

Importance Germline mutations in BRCA1 and BRCA2 are relatively common in women with ovarian, fallopian tube, and peritoneal carcinoma (OC) causing a greatly increased lifetime risk of these cancers, but the frequency and relevance of inherited mutations in other genes is less well characterized.Objective To determine the frequency and importance...

s: AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; March 5-8, 2015; Orlando, FL Background: Targeting ovarian cancer vasculature by humanized VEGFA neutralizing antibody bevacizumab has been demonstrated effective in multiple randomized phase III clinical studies to improve standard chemother...

Objective: To estimate the probability of complete clinical response and toxicity of paclitaxel as second-line chemotherapy in measurable disease patients with malignant tumors of the ovarian stroma, and to evaluate the value of inhibin for predicting response. Methods: Thirty-one patients with histologically confirmed ovarian stromal tumor were...

For the past 60 years, the gold standard for assessing a new treatment’s efficacy is the randomized phase III trial. When properly designed, conducted, and reported, these studies can provide level-1 evidence that a new treatment is, on average, more effective than standard treatment in a patient population. This trial design does have some limitat...

To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus plac...

Objective: To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods: A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results: Clinical trial endpoints have profound effec...

Gynecologic Oncology Group Study 0218 (GOG-0218), a phase III, placebo-controlled trial in newly diagnosed stage III/IV ovarian cancer (OC), demonstrated a benefit in investigator (INV)-assessed progression-free survival (PFS) with bevacizumab (BEV) administered with and following carboplatin/paclitaxel (CP) for up to 15 months vs. CP alone. To det...

Background Granulocyte colony stimulating factor (G-CSF) and erythropoietin stimulating agents (ESA) may be used to support patients during chemotherapy. We assessed whether G-CSF or ESA were associated with progression or death in patients with ovarian cancer.Methods Patients with ovarian cancer following surgery, were on a protocol to evaluate be...

Previous studies have shown that vascular endothelial growth factor (VEGF) promotes progression in epithelial ovarian cancer and that blockade of VEGF inhibits growth of this tumor and metastasis. Bevacizumab is a humanized anti-VEGF monoclonal antibody that has single-agent activity in women with recurrent ovarian tumors. This multinational double...

CA125 is a non-specific marker of peritoneal irritation which has the potential for false elevation during intraperitoneal treatment. The purpose of this study is to identify the rate of CA125 regression during intraperitoneal (IP) versus intravenous (IV) chemotherapy for ovarian cancer. GOG 114, a randomized control trial evaluating IP and IV trea...

Vascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line...

AMO has participated on advisory boards for AstraZeneca, Celgene Corporation, and Sanofi–Aventis. [...]

Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To date, overall survival (os) has been the most-used endpoint in oncology trials because of its relevance and objectivity. However, as a result of various factors, including the pattern of sequential salvage therapies, measurement of os and collection of os data are becomin...

Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To date, overall survival (os) has been the most-used endpoint in oncology trials because of its relevance and objectivity. However, as a result of various factors, including the pattern of sequential salvage therapies, measurement of os and collection of os data are becomin...

To compare the recurrence-free interval (RFI) and safety profile in patients with completely resected high-risk early-stage ovarian cancer treated with intravenous (IV) carboplatin and paclitaxel with or without maintenance low-dose paclitaxel for 24 weeks. Eligibility was limited to patients with stage IA/B (grade 3 or clear cell), all IC or II ep...

5023 Background: GOG218 is a phase III randomized, double-blind, placebo-controlled trial with three arms comparing both carboplatin and paclitaxel (CP) plus concurrent, or concurrent plus continued BEV (CP+B-->B) in stage III (with macroscopic residual disease) and stage IV EOC, PPC or FTC. Investigator assessment showed a clinically meaningful an...

Previous studies report a survival advantage in ovarian cancer patients with Ashkenazi Jewish (AJ) breast cancer gene (BRCA) founder mutations. The purpose of this study was to determine if this association exists in patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations. We also sought to account for "survival bias" by minimizing lead time tha...

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups...

Primary mucinous adenocarcinomas of the ovary are uncommon, and their biological behavior is uncertain. Retrospective studies have suggested that many mucinous carcinomas initially diagnosed as primary to the ovary have in fact metastasized from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucino...

Research Highlights ► Within this randomized trial a statistical benefit was seen with primary surgery among patients with less than 5 cm of upper abdominal disease (HR 0.64). ► Across different countries in this study there was significant heterogeneity of the benefit of primary cytoreductive surgery.

Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials. An immunohistochemistry assay was used to detect p27 in formalin-fixed paraffin-embedded ovarian tumors...

To compare progression-free survival (PFS), overall survival (OS) and toxicities of thalidomide versus tamoxifen and to evaluate serum vascular endothelial growth factor (VEGF) in biochemical-recurrent epithelial ovarian cancer, primary peritoneal cancer or fallopian tube carcinoma (EOC/PPC/FTC). Biochemical recurrence was defined as a rising CA-12...

Epithelial ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. Although the prevalence of ovarian cancer when compared with other neoplasms is low, with an estimated 21,550 new cases in 2009, the majority of patients are diagnosed at an advanced stage of disease, with projected 5-year relative survival r...

The prognostic relevance of uncommon epithelial ovarian cancer (EOC) histological subtypes remains controversial. The Gynecologic Cancer InterGroup (GCIG) initiated this meta-analysis to assess the relative prognosis of women with a diagnosis of rare EOC histologies from completed, prospectively randomized studies performed by cooperative GCIG stud...

LBA1 Background: BEV, a humanized anti-VEGF monoclonal antibody, has demonstrated single-agent activity in patients with recurrent EOC, or PPC. The therapeutic impact of concurrent ± maintenance BEV with standard chemotherapy (CT) was evaluated in an international, double-blind, placebo-controlled phase III trial. Methods: Eligible patients had new...

Background: After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated and some important clinical questions were unanswered. Objectives: We initiated a meta-ana...

The appropriate therapy for patients with localized (FIGO Stage I and II) ovarian cancer has been poorly defined for all age groups and particularly for the elderly. Few prospective randomized comparisons of adjuvant therapy after careful surgical staging have been performed. The Gynecologic Oncology Group (GOG) has performed a series of trials tes...

In this note we outline 15 years of Gynecologic Oncology Group (GOG) experience conducting a series of phase II second-line intraperitoneal trials in the treatment of ovarian cancer. Using this information, the goal is to define a new permutation approach to historical control phase II trials in ovarian cancer. We utilize seven previous phase II GO...

e16544 Background: An R software library was created with the goal of creating customizable, platform independent, and portable visualization tools for the annotation, dissemination and interrogation of high dimensioned genomic data. Methods: A set of R functions were created to extend the functionality of the sendplot R library. The functions were...

To determine if incorporation of an additional cytotoxic agent improves overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma who receive carboplatin and paclitaxel. Women with stages III to IV disease were stratified by coordinating center, maxima...

To assess the association between patient-disease characteristics and overall survival (OS) after second-line intraperitoneal (IP) treatment of ovarian cancer. Data were aggregated from 7 Gynecologic Oncology Group (GOG) phase 2 studies conducted between 1988 and 1995 to evaluate IP therapy for partially responsive or recurrent disease but no tumor...

Background: After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered. Patients and methods: We initiated...

Despite both the increase in basic biologic knowledge and the fact that many new agents have reached various stages of development during the last 10 years, the number of new treatments that have been approved for patients has not increased as expected. We propose the multi-arm, multi-stage trial design as a way to evaluate treatments faster and mo...

After initial surgery, there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma (CS). This study was designed to compare patient outcome following treatment with adjuvant whole abdominal irradiation (WAI) versus (vs.) chemotherapy for patients with this rare group of female pelvic malignancies. E...

This study was undertaken to assess if prolonged paclitaxel administration in combination with cisplatin improves overall survival (OS) in epithelial ovarian cancer (EOC). Eligible patients with suboptimal stage III or IV EOC, fallopian tube, or primary peritoneal cancer were randomly allocated to receive six cycles of cisplatin 75 mg/m2 and either...

For ovarian cancer patients receiving maintenance treatment after complete clinical response to primary therapy, we tested the predictive value of the following early signal of progressive disease (EPD) criterion based on serum CA-125: for patients with CA-125 nadir <or= 10 U/mL, a confirmed value of >or= 20 U/mL serves as an early signal of CA-125...