Trials in progress: IMagyn050/GOG 3015/ENGOT-OV39. A Phase III, multicenter, randomized study of atezolizumab versus placebo administered in combination with paclitaxel, carboplatin, and bevacizumab to patients with newly-diagnosed stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer

2019 ◽  
Vol 29 (2) ◽  
pp. 430-433 ◽  
Author(s):  
Kathleen N Moore ◽  
Sandro Pignata
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Fallopian Tube ◽  
Residual Disease ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Controlled Study ◽  
Free Survival

BackgroundThere is mounting pre-clinical and clinical evidence that combinations of immunotherapy, specifically programed cell death-1 (PD-1) inhibition, with chemotherapy and anti-angiogenesis agents, such as bevacizumab, result in markedly improved outcomes across a variety of tumor types including endometrial cancer, renal cell cancer, and non-small cell lung cancer. IMagyn050/GOG 3015/ENGOT-OV39 is the first, randomized, phase III trial to evaluate the potential impact of this combination on both progression-free survival and overall survival in patients presenting with advanced epithelial ovarian cancer.Primary ObjectiveThe primary objective is to evaluate the efficacy of atezolizumab versus placebo in combination with paclitaxel + carboplatin + bevacizumab for front-line treatment of ovarian cancer among all patients and those with PD-L1+ tumors.Study HypothesisThis study will test the hypothesis that treatment with atezolizumab added to paclitaxel, carboplatin, and bevacizumab will prolong progression-free survival and overall survival compared with treatment with placebo plus paclitaxel, carboplatin, and bevacizumab.Trial DesignThis is a randomized, phase III, placebo-controlled study.Major Inclusion/Exclusion CriteriaEligible patients have a histologic diagnosis of advanced epithelial ovarain cancer, primary peritoneal, or fallopian tube cancer who either have residual disease after primary surgery or who are undergoing neoadjuvant chemotherapy with planned interval surgery. Ineligible patients include those who are cured with surgery alone or those for whom no gross residual disease remained following primary cytoreduction.Primary EndpointThere are two co-primary efficacy endpoints: investigator-assessed progression-free survival and overall survival.Sample Size1300 patients.Estimated Dates for Completing Accrual and Presenting ResultsApril 2020.Trial RegistrationNCT03038100.

Does endometriosis have an effect on the survival of women with synchronous endometrial and ovarian cancer?

2019 ◽  
Vol 11 (4) ◽  
pp. 185-193
Author(s):  
Engin Celik ◽  
Hale Goksever Celik ◽  
Hamdullah Sozen ◽  
Semen Onder ◽  
Merve Baktiroglu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Detrimental Effect ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
Pathological Characteristics

Purpose: Synchronous endometrial and ovarian cancer is defined as the concurrent presence of ovarian cancer with endometrial cancer. We aimed to evaluate whether there is an effect of endometriosis on progression-free survival and overall survival of women with synchronous endometrial and ovarian cancer. We also compared these findings with the patients having endometrial-only tumors and ovarian-only tumors. Methods: The patients who underwent surgery for endometrioid or clear-cell endometrial-only tumors and/or ovarian-only tumors and synchronous endometrial and ovarian cancer between 2005 and 2016 were included in this cohort study. The effect of the presence of endometriosis on progression-free survival and overall survival in these women who met the criteria was determined using statistical methods. Women were also compared regarding their demographic, clinical, and pathological characteristics. Results: A total of 176 patients were included in this study. All histology types of tumors located in endometrium or ovary were endometrioid or clear-cell cancer. Endometriosis was present in 62 patients (35.2%), whereas adenomyosis was present in 44 patients (25%). Endometriosis was diagnosed more frequently in women with ovarian-only tumors and synchronous endometrial and ovarian cancer than those with endometrial-only tumors (59.2% vs 5.7%, p < 0.001 and 45.7% vs 5.7%, p < 0.001, respectively). The patients with endometriosis showed no significantly longer progression-free survival and overall survival (hazard ratio = 1.70; 95% confidence interval = 0.48–6.03; p = 0.408 and hazard ratio = 1.67; 95% confidence interval = 0.30–9.44; p = 0.562, respectively). The presence of endometriosis was a stronger predictor for progression-free survival and overall survival comparing with the presence of adenomyosis. Conclusion: The women with synchronous endometrial and ovarian cancer should be informed that endometriosis has no detrimental effect on progression-free survival and overall survival.

Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer

2004 ◽  
Vol 22 (8) ◽  
pp. 1430-1438 ◽  
Author(s):  
E. Van Cutsem ◽  
H. van de Velde ◽  
P. Karasek ◽  
H. Oettle ◽  
W.L. Vervenne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Survival Rates ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Free Survival

Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m2 intravenously weekly × 7 for 8 weeks, then weekly × 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade ≥ 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.

scholarly journals Stereotactic Body Radiation Therapy for Oligometastatic Breast Cancer: A Retrospective Multicenter Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Pauline Lemoine ◽  
Marie Bruand ◽  
Emmanuel Kammerer ◽  
Emilie Bogart ◽  
Pauline Comte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Progression Free Survival ◽  
High Volume ◽  
Primary Objective ◽  
Phase Iii ◽  
Study Phase ◽  
Breast Cancer Patients ◽  
Free Survival

IntroductionStereotactic radiotherapy may improve the prognosis of oligometastatic patients. In the literature, there is very little data available that is specific to breast cancer.Materials and MethodsWe conducted a multicenter retrospective study. The primary objective was to estimate progression-free survival after stereotactic body radiotherapy (SBRT) using Cyberknife of breast cancer oligometastases. The secondary objectives were to estimate overall survival, local control, and toxicity. The inclusion criteria were oligometastatic breast cancer with a maximum of five lesions distributed in one to three different organs, diagnosed on PET/CT and/or MRI, excluding brain metastases and oligoprogressions. This was combined with systemic medical treatment.FindingsForty-four patients were enrolled from 2007 to 2017, at three high-volume cancer centers. The patients mostly had one to two lesion(s) whose most widely represented site was bone (24 lesions or 44.4%), particularly in the spine, followed by liver (22 lesions or 40.7%), then pulmonary lesions (six lesions or 11.1%). The primary tumor expressed estrogen receptors in 33 patients (84.6%); the status was HER2+++ in 7 patients (17.9%). The median dose was 40 Gy (min-max: 15-54) prescribed at 80% isodose, the median number of sessions was three (min-max: 3-10). The median D50% was 42 Gy (min max 17-59). After a median follow-up of 3.4 years, progression-free survival (PFS) at one year, two years, and three years was 81% (95% CI: 66-90%), 58% (95% CI: 41-72%), and 45% (95% CI: 28-60%), respectively. The median PFS was 2.6 years (95% CI: 1.3 – 4.9). Overall survival at three years was 81% (95% CI: 63-90%). The local control rate at two and three years was 100%. Three patients (7.3%) experienced G2 acute toxicity, no grade ≥3 toxicity was reported.ConclusionThe PFS of oligometastatic breast cancer patients treated with SBRT appears long, with low toxicity. Local control is high. SBRT for oligometastases is rarely applied in breast cancer in light of the population in our study. Phase III studies are ongoing.

scholarly journals Primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: OVHIPEC-2, a phase III randomized clinical trial

2020 ◽  
Vol 30 (6) ◽  
pp. 888-892 ◽  
Author(s):  
Simone Koole ◽  
Ruby van Stein ◽  
Karolina Sikorska ◽  
Desmond Barton ◽  
Lewis Perrin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Residual Disease ◽  
Figo Stage ◽  
Primary Objective ◽  
Phase Iii ◽  
Stage Iii

BackgroundThe addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery. The effect of HIPEC remains undetermined in patients who are candidates for primary cytoreductive surgery.Primary objectiveThe primary objective is to evaluate the effect of HIPEC on overall survival in patients with FIGO stage III epithelial ovarian cancer who are treated with primary cytoreductive surgery resulting in no residual disease, or residual disease up to 2.5 mm in maximum dimension.Study hypothesisWe hypothesize that the addition of HIPEC to primary cytoreductive surgery improves overall survival in patients with primary FIGO stage III epithelial ovarian cancer.Trial designThis international, randomized, open-label, phase III trial will enroll 538 patients with newly diagnosed FIGO stage III epithelial ovarian cancer. Following complete or near-complete (residual disease ≤2.5 mm) primary cytoreduction, patients are randomly allocated (1:1) to receive HIPEC or no HIPEC. All patients will receive six courses of platinum-paclitaxel chemotherapy, and maintenance PARP-inhibitor or bevacizumab according to current guidelines.Major eligibility criteriaPatients with FIGO stage III primary epithelial ovarian, fallopian tube, or primary peritoneal cancer are eligible after complete or near-complete primary cytoreductive surgery. Patients with resectable umbilical, spleen, or local bowel lesions may be included. Enlarged extra-abdominal lymph nodes should be negative on FDG-PET or fine-needle aspiration/biopsy.Primary endpointThe primary endpoint is overall survival.Sample sizeTo detect a HR of 0.67 in favor of HIPEC, 200 overall survival events are required. With an expected accrual period of 60 months and 12 months additional follow-up, 538 patients need to be randomized.Estimated dates for completing accrual and presenting resultsThe OVHIPEC-2 trial started in January 2020 and primary analyses are anticipated in 2026.Trial registrationClinicalTrials.gov:NCT03772028

Randomized phase III study of gemcitabine and cisplatin (GC) versus dose dense methotrexate, vinblastine, doxorubicin and cisplatin (DD-MVAC) in the perioperative setting for patients with locally advanced transitional cell cancer of the bladder: The French GETUG/AFU V05 VESPER trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS530-TPS530 ◽  
Author(s):  
Christian Pfister ◽  
Gwenaelle Gravis ◽  
Geraldine Pignot ◽  
Aude Flechon ◽  
Michel Soulie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cell Cancer ◽  
Transitional Cell ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Cancer Of The Bladder ◽  
Transitional Cell Cancer ◽  
Phase Iii Study

TPS530 Background: Radical cystectomy remains the gold standard treatment for invasive non metastatic transitional cell cancer of the bladder. Perioperative chemotherapy (adjuvant ou neoadjuvant) has been developed to increase overall survival. However, the chemotherapy administration time and optimal chemotherapy regimen are not yet determined. As DD-MVAC has been shown to be associated with higher response rates in bladder metastatic disease, also a better efficacy can be suspected in the perioperative setting. Methods: We designed a randomized phase III study to compare the efficacy of GC and DD-MVAC in term of progression-free survival in patients for whom chemotherapy has been decided, before or after radical cystectomy (disease defined by a T2, T3 or T4a N0 M0 stadification for patients receiving neoadjuvant chemotherapy or pT3 or pT4 or pN+ and M0 for patients receiving adjuvant chemotherapy). Secondary endpoints include overall survival, side effects, response rate in the neoadjuvant setting. Main exclusion criteria were histological variants (pure adenocarcinoma or pure epidermoid carcinoma or pure or mixed small-cell neuro-endocrine carcinoma) and ventricular ejection fraction under 50%. The total number of patients projected was 500 based on the median progression-free survival rate of 50% at 3 years observed in patients treated with GC (standard arm A) in the perioperative setting. An absolute improvement of 10% (HR = 0.74) was expected with DD-MVAC (experimental arm B) with a = 0.05 and b = 0.20. In October 2017, 460 patients have been included. An interim analysis is planned after the occurrence of 174 events. With an estimated uniform accrual rate of 140 patients per year for 3.5 years and exponential survival, the final analysis is expected to occur 8 years after the start of the trial. Concomitant ancillary study has also started, focusing on the identification of subgroups for muscle invasive bladder tumors sensitivity to neoadjuvant chemotherapy, as suggested by the recent MDA classification. Clinical trial information: NCT 018 12369.

Intraperitoneal paclitaxel and cisplatin compared with dose-dense paclitaxel and carboplatin for patients with stage III ovarian cancer

2020 ◽  
Vol 26 (7) ◽  
pp. 1566-1574 ◽  
Author(s):  
Madison Murphy ◽  
Grace Martin ◽  
Zahra Mahmoudjafari ◽  
Cory Bivona ◽  
Dennis Grauer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Primary Objective ◽  
Stage Iii ◽  
Free Survival ◽  
Intraperitoneal Therapy ◽  
Dose Dense

Introduction Patients diagnosed with stage III ovarian cancer are at high risk of recurrence and optimal adjuvant therapy is often debated. There is limited literature that directly compares intraperitoneal paclitaxel and cisplatin with dose-dense paclitaxel and carboplatin. Objectives The primary objective was to compare progression-free survival, overall survival, and tolerability of adjuvant intraperitoneal paclitaxel and cisplatin to dose-dense paclitaxel and carboplatin in stage III ovarian cancer patients. Methods A retrospective, IRB-approved, single center chart review was conducted reviewing adult patients with stage III ovarian cancer undergoing adjuvant intraperitoneal therapy or dose-dense therapy between 2010 and 2018. Results Eighty-two patients were included in the final analysis; 44 in the intraperitoneal group and 38 in the dose-dense group. Intraperitoneal therapy was not associated with a longer progression-free survival (35.4 vs. 31.1 months; P = 0.97). The duration of overall survival did not differ between intraperitoneal and dose-dense (56.3 vs. 54.5 months; P = 0.55). Dose reductions were less frequent with intraperitoneal than dose-dense (11.36% vs. 31.58%; P = 0.02). No difference in treatment delays (45.5% vs. 65.8%; P = 0.07), dose cancellations (59.1% vs. 57.9%; P = 0.91), supportive care additions (95.5% vs. 84.2%; P = 0.09), or therapy discontinuation (59.1% vs. 39.5%; P = 0.07) between groups was noted. Conclusions Intraperitoneal therapy with paclitaxel and cisplatin, as compared with dose-dense paclitaxel and carboplatin, did not prolong progression-free or overall survival in the adjuvant setting among stage III ovarian cancer patients. A trend towards decreased tolerability was noted with intraperitoneal therapy.

Phase III Trial of Standard-Dose Intravenous Cisplatin Plus Paclitaxel Versus Moderately High-Dose Carboplatin Followed by Intravenous Paclitaxel and Intraperitoneal Cisplatin in Small-Volume Stage III Ovarian Carcinoma: An Intergroup Study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group

2001 ◽  
Vol 19 (4) ◽  
pp. 1001-1007 ◽  
Author(s):  
Maurie Markman ◽  
Brian N. Bundy ◽  
David S. Alberts ◽  
Jeffrey M. Fowler ◽  
Daniel L. Clark-Pearson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Relative Risk ◽  
Small Volume ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Free Survival

PURPOSE: To compare the progression-free and overall survival in small-volume residual ovarian cancer after treatment with intravenous (IV) cisplatin and paclitaxel or an experimental regimen of IV carboplatin followed by IV paclitaxel and intraperitoneal cisplatin. PATIENTS AND METHODS: Patients were randomized to receive either IV paclitaxel 135 mg/m2 over 24 hours followed by IV cisplatin 75 mg/m2 every 3 weeks for six courses or IV carboplatin (area under curve 9) every 28 days for two courses, then IV paclitaxel 135 mg/m2 over 24 hours followed by intraperitoneal (IP) cisplatin 100 mg/m2 every 3 weeks for six courses. RESULTS: Of the 523 patients who entered this trial, 462 were determined to be assessable, with prognostic factors well balanced between the treatments. Neutropenia, thrombocytopenia, and gastrointestinal and metabolic toxicities were greater in the experimental arm. As a result, 18% of the patients received ≤ two courses of IP therapy. Progression-free survival was superior for patients randomized to the experimental treatment arm (median, 28 v 22 months; relative risk, 0.78; log-rank P = .01, one-tail). There was a borderline improvement in overall survival associated with this regimen (median, 63 v 52 months; relative risk, 0.81; P = .05, one-tail). CONCLUSION: An experimental regimen including moderately high-dose IV carboplatin followed by IP paclitaxel and IV cisplatin yielded a significant improvement in progression-free survival when compared with a standard regimen of IV cisplatin and paclitaxel. Because the improvement in overall survival was of borderline statistical significance and toxicity was greater, the experimental arm is not recommended for routine use. However, the results provide direction for further clinical investigation in small-volume ovarian cancer.

Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: Follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8027-8027
Author(s):  
Othman Al-Sawaf ◽  
Can Zhang ◽  
Maneesh Tandon ◽  
Arijit Sinha ◽  
Anna Maria Fink ◽  
...  
Keyword(s):  
Overall Survival ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Fixed Duration ◽  
Free Survival ◽  
To Receive ◽  
Minimal Residual

8027 Background: The CLL14 trial demonstrated significant improvement of progression-free survival (PFS) with fixed-duration venetoclax-obinutuzumab (VenG) as compared to chlorambucil-obinutuzumab (ClbG) in patients with previously untreated CLL and coexisting conditions. Here, we report follow-up data on safety and efficacy. Methods: Patients with previously untreated CLL and coexisting conditions were randomized 1:1 to receive 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab. Primary endpoint was investigator-assessed progression-free survival. Key secondary endpoints were response rates, rates of minimal residual disease (measured every 6 months up to 5 years after last patient enrolment) and overall survival. Follow-up is ongoing but all patients are off study treatment. This trial was registered with ClinicalTrials.gov, number NCT02242942. Results: Of the 432 enrolled patients, 216 were randomly assigned to receive VenG and 216 to receive ClbG. After a median follow-up of 39.6 months (interquartile range 36.75 - 43.04), progression-free survival continued to be superior for VenG as compared to ClbG (median not reached vs 35.6 months; hazard ratio [HR] 0.31 [0.22-0.44], p < 0.001). At 3 years, the estimated progression-free survival rate was 81.9% in the VenG arm and 49.5% in the ClbG arm. This benefit was consistently observed across all clinical and biological risk groups, including patients with TP53 mutation/deletion and unmutated IGHV status. Of note, PFS was also significantly longer for VenG treated patients with mutated IGHV status. Assessment of minimal residual disease 18 months after end of treatment showed that 47.2% of patients in the VenG arm had undetectable (u) uMRD ( < 10−4), 13% had low (L)-MRD (≥ 10−4 and < 10−2) and 7.9% high (H)-MRD (≥ 10−2), compared to 7.4% uMRD, 17.1% L-MRD, 26.9% H-MRD in the ClbG arm. No difference has been observed (HR 1.027, 95% CI 0.602-1.753, p = 0.921) for overall survival; median overall survival has not been reached in either group. Second primary malignancies were reported in 36 (17%) patients in the VenG arm and 22 (10.3%) in the ClbG arm. No new safety signals were observed. Conclusions: The results suggest that the superior efficacy and deep remissions after fixed-duration VenG are maintained during extended follow-up, and show the long-term benefits of 12 cycles of VenG across all known risk categories. Clinical trial information: NCT02242942 .

scholarly journals ICON 9—an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy

2020 ◽  
Vol 31 (1) ◽  
pp. 134-138
Author(s):  
Osnat Elyashiv ◽  
Jonathan Ledermann ◽  
Gita Parmar ◽  
Laura Farrelly ◽  
Nicholas Counsell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Wild Type ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Primary Endpoints ◽  
Platinum Based Chemotherapy

BackgroundTwo novel biological agents—cediranib targeting angiogenesis, and olaparib targeting DNA repair processes—have individually led to an improvement in ovarian cancer control. The aim of ICON9 is to investigate the combination of cediranib and olaparib maintenance in recurrent ovarian cancer following platinum-based therapy.Primary objectiveTo assess the efficacy of maintenance treatment with olaparib in combination with cediranib compared with olaparib alone following a response to platinum-based chemotherapy in women with platinum-sensitive ovarian, fallopian tube or peritoneal cancer during first relapse.Study hypothesisMaintenance therapy with cediranib and olaparib in combination is associated with improved patient outcomes compared with olaparib alone.Trial designInternational phase III randomized controlled trial. Following a response to platinum-based chemotherapy patients are randomized 1:1 to either oral olaparib and cediranib (intervention arm) or oral olaparib alone (control arm).Major inclusion criteriaPatients with a known diagnosis of high grade serous or endometrioid carcinoma of the ovary, fallopian tube or peritoneum, progressing more than 6 months after first-line platinum-based chemotherapy, who have responded to second-line platinum-based chemotherapy.Primary endpointsProgression-free and overall survival. Co-primary endpoints to be assessed using a fixed-sequence gatekeeping approach: (1) progression-free survival, all patients; (2) progression-free survival, BRCA wild type; (3) overall survival, all patients; (4) overall survival, BRCA wild type.Sample size618 patients will be recruited.Estimated dates for completing accrual and presenting resultsAccrual is expected to be completed in 2024 with presentation of results in 2025.Trial registrationClinicalTrials.gov: NCT03278717.

Real world outcomes in platinum sensitive relapsed ovarian, fallopian tube, or peritoneal cancer treated in routine clinical practice in the United Kingdom prior to poly-ADP ribose polymerase inhibitors

2020 ◽  
Vol 30 (7) ◽  
pp. 1026-1033
Author(s):  
Rosemary Lord ◽  
Jyoti Rauniyar ◽  
Tamsin Morris ◽  
Orlaith Condon ◽  
Rachel Jones ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Real World ◽  
Index Date ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Polymerase Inhibitors

IntroductionThe introduction of poly-ADP ribose polymerase inhibitors in ovarian cancer has demonstrated significantly improved progression free survival in four randomized controlled clinical trials in patients with platinum sensitive relapsed ovarian cancer. While overall survival data remain immature, this real world evidence study sets a baseline for future evaluation of poly-ADP ribose polymerase inhibitors.MethodsA retrospective chart review was undertaken to investigate real world survival outcomes across 13 National Health Service Trusts in England, Wales, and Scotland. Patients were included if they had platinum sensitive relapsed high grade serous ovarian cancer and had responded to secondline platinum based chemotherapy. Clinical data were collected retrospectively from electronic prescribing records and chart notes. The index date for overall survival analysis was defined as the later of (1) day 1 of the final secondline platinum based treatment or (2) date of response to secondline treatment. The primary objective was overall survival from the index date. Secondary objectives included progression free survival and overall survival by subsequent line of treatment. BRCA mutation status was collected where available. Quality of life questionnaires were not assessed within this study.Results233 patients were identified who met the study inclusion criteria. Patient characteristics were consistent with other published data, with a median age of 61 years (range 35–85). Sensitivity analysis of the primary objective demonstrated that the earliest point poly-ADP ribose polymerase inhibitors may be initiated (following completion of secondline chemotherapy) is associated with a median overall survival of 19.8 months. Secondline median overall survival and progression free survival from the index date were 19.3±2.4 months and 7.3±1.2 months, respectively. 144 patients were treated with thirdline chemotherapy with median overall survival and progression free survival from the index date (either date of last cycle of thirdline treatment or date of response to thirdline treatment) of 8.3±2.6 and 4.4±1.8 months, respectively.ConclusionOverall survival was shown to be shorter in this real world study compared with randomized clinical trials, and underlines the differences in clinical outcomes of patients in a real life setting. This baseline real world study has demonstrated poor survival outcomes in this patient group prior to availability of poly-ADP ribose polymerase inhibitors.

Sign in / Sign up

Export Citation Format

Share Document