Prognostic impact of the time interval between primary surgery and start of first-line chemotherapy in patients with advanced ovarian cancer: Analysis of prospective randomized phase III trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5514-5514
Author(s):  
S. Mahner ◽  
A. Staehle ◽  
C. zu Eulenburg ◽  
K. Wegscheider ◽  
A. Reuss ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Advanced Ovarian Cancer ◽  
Residual Tumor ◽  
Phase Iii ◽  
Time Interval ◽  
Prognostic Impact ◽  
First Line ◽  
Primary Surgery ◽  
Line Chemotherapy

5514 Background: Primary surgery followed by platinum-taxane chemotherapy is the standard therapy of advanced ovarian cancer. It is not clear, whether the time interval between surgery and start of first line chemotherapy (time to chemo - TTC) has an impact on the clinical outcome. Methods: Individual patient data meta-analysis of three prospective randomized AGO-OVAR/GINECO trials (AGO OVAR 3, 5, and 7) conducted between 1995 and 2002 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Cox proportional hazard models were applied to evaluate the prognostic impact of different variables on survival; TTC was introduced as a continuous variable. Results: A total of 3,326 patients were analyzed. Chemotherapy was started within 8 weeks after surgery. Median progression-free survival (PFS) was 17.91 months (95% CI: 17.15–18.73 months) and median overall survival (OS) 37.83 months (95% CI: 36.57–38.90 months). The median TTC was 19 days (95% CI: 18–19 days, range 1–56 days). By multivariate analysis of the total cohort, there was no significant association between TTC and PFS (p = 0.131) or OS (p = 0.372). In the subgroup of patients with no residual tumor after debulking surgery (n = 1.101), a significant and independent correlation between early start of chemotherapy and improved overall survival was observed (p = 0.022). Conclusions: Our analysis represents the largest study investigating treatment delivery and outcome in ovarian cancer. The time interval between primary surgery and start of first line chemotherapy seems to have no general impact in all patients. However, it could be demonstrated for the first time that a delayed start of chemotherapy was independently associated with decreased overall survival in patients with complete surgical debulking. As previously shown for other biological factors in ovarian cancer, the presence of residual tumor after surgery seems to prevail over the prognostic impact of therapy initiation. No significant financial relationships to disclose.

Carboplatin (C) plus paclitaxel (P) versus carboplatin plus pegylated liposomal doxorubicin (PLD) in patients with advanced ovarian cancer (AOC): Final analysis of the MITO-2 randomized multicenter trial.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA5033-LBA5033 ◽  
Author(s):  
S. Pignata ◽  
G. Scambia ◽  
A. Savarese ◽  
R. Sorio ◽  
E. Breda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Response Rate ◽  
Multivariable Analysis ◽  
Advanced Ovarian Cancer ◽  
Final Analysis ◽  
Phase Iii ◽  
P Value ◽  
First Line ◽  
Significant Difference ◽  
Line Chemotherapy

LBA5033 Background: CP is standard first-line chemotherapy for AOC. MITO-2 (Multicentre Italian Trials in Ovarian Cancer) is an academic multicenter randomized phase III study, testing whether C-PLD is more effective than CP. Methods: AOC chemo-naïve patients (pts), stage IC-IV, aged≤75, ECOG PS≤2, were randomized to CP (C AUC5 + P 175 mg/m2,d1q3w) or to C-PLD (C AUC5 + PLD 30 mg/m2,d1q3w), both for 6 cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate, toxicity and quality of life (QoL). To have 80% power in detecting a 0.80 HR in PFS, with 2-sided α error 0.05, 632 events were needed and 820 pts were planned. Response rate and toxicity have been reported at ASCO 2009 (abs #LBA5508). All analyses are based on intention to treat. Results: From Jan ’03 to Nov ’07, 820 pts were randomized, 410 to each arm. Median age was 57 yrs (range 21-77). Stage III (60%) and IV (21%) were prevalent. A plateau in PFS events was reached before obtaining the planned number. Thus, following an IDMC recommendation, the final analysis was done with 556 events occurred as of December 31, 2009. This size is consistent with HR to be detected equal to 0.79, with 80% power. With a median follow-up of 40.2 months, median PFS was 19.0 and 16.8 months with C-PLD and CP, respectively (HR 0.95, 95%CI 0.81-1.13, log-rank p value=0.58). Lack of significant difference was confirmed (HR 0.96, 95%CI 0.81-1.14) at multivariable analysis adjusted by stage, PS, residual disease, age and size of the institution. There was no heterogeneity of treatment effect among major subgroups. With 313 deaths recorded, median OS was 61.6 and 53.2 months with C-PLD and CP, respectively (HR 0.89, 95%CI 0.72-1.12, log-rank p value=0.32). QoL data will be presented at the meeting. Conclusions: In the MITO-2 trial, C-PLD was not found to be superior to CP, which remains the standard first-line chemotherapy for AOC.However, given the observed confidence interval and the different toxicity profile, C-PLD could be considered an alternative to standard therapy. Study was partially supported by Schering-Plough. [Table: see text]

First-Line Chemotherapy With Epirubicin, Paclitaxel, and Carboplatin for Advanced Ovarian Cancer: A Phase I/II Study of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group

1999 ◽  
Vol 17 (1) ◽  
pp. 46-46 ◽  
Author(s):  
A. du Bois ◽  
H. J. Lück ◽  
T. Bauknecht ◽  
W. Meier ◽  
B. Richter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Survival Rates ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
First Line ◽  
Gynäkologische Onkologie ◽  
Combination Regimens ◽  
Level 2 ◽  
Line Chemotherapy

PURPOSE: Despite the progress that has been achieved over the years, survival rates in patients with advanced ovarian cancer are still disappointing. New methods to improve the efficiency of first-line chemotherapy are warranted. One method to improve results is to add more non–cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines are among the candidates for incorporation as the “third drug” into first-line regimens for advanced ovarian cancer. PATIENTS AND METHODS: We performed a phase I/II trial with escalating doses of epirubicin (60, 75, and 90 mg/m2) combined with fixed doses of paclitaxel and carboplatin in 27 previously untreated patients with advanced gynecologic malignancies. RESULTS: Dose-limiting toxicity occurred at dose level 2 (75 mg/m2 epirubicin) and consisted of myelosuppression (neutropenia, thrombocytopenia). No dose-limiting, nonhematologic toxicities were observed. The maximum tolerable dose was epirubicin 60 mg/m2 (E) combined with a 3-hour infusion of paclitaxel 175 mg/m2 (T) and carboplatin AUC 5 (Carbo). Preliminary analysis indicated promising activity against ovarian cancer. CONCLUSION: The three-drug combination ET-Carbo, given according to the outlined dose and schedule, should be considered for further phase III evaluation. A randomized German-French intergroup trial comparing ET-Carbo with carboplatin-paclitaxel has already been initiated.

NOGGO Ov-42/MAMOC: Rucaparib maintenance after bevacizumab maintenance following carboplatin-based first line-chemotherapy in ovarian cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6102-TPS6102
Author(s):  
Elena Ioana Braicu ◽  
Pauline Wimberger ◽  
Rolf Richter ◽  
Maren Keller ◽  
Petra Krabisch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Residual Tumor ◽  
Phase Iii ◽  
High Grade ◽  
First Line ◽  
Tumor Mass ◽  
Antiangiogenic Drugs ◽  
Line Chemotherapy ◽  
Residual Tumor Mass

TPS6102 Background: Ovarian cancer (OC) is associated with the highest mortality rates among gynecological malignancies, with most patients being diagnosed in advanced stages. The most common histological subtype is high grade serous OC, which is characterized by deficiency in homologous recombination. Debulking surgery, followed by platinum based chemotherapy and bevacizumab (bev), followed by maintenance therapy with bev, is the standard therapy for advanced BRCA wild type (BRCAwt) OC patients in Germany. BRCA mutant patients will receive maintenance with olaparib, according to SOLO1 data. The anticancer effects of PARP inhibitors (PARPi) seem to be increased by the addition of antiangiogenic drugs. Preclinical data showed increased HRD in tumors pretreated with bev, and clinical trials showed a benefit of the combination of antiangiogenic drugs and PARPi vs. PARPi alone. NOGGO Ov-42/MAMOC trial (NCT04227522) is a phase III, randomized, placebo-controlled study evaluating rucaparib maintenance following bevacizumab maintenance for the treatment of advanced primary high grade BRCAwt OC. Methods: 190 patients with histologically confirmed advanced (FIGO stage IIIA- IV of the 2014 FIGO classification) high grade serous or high grade endometrioid (based on local histopathological findings) OC, fallopian tube cancer, primary peritoneal cancer or clear cell carcinoma of the ovary will be randomized 2:1 to receive either rucaparib 600mg BID or placebo as maintenance therapy following first line chemotherapy with 6 cycles of Carboplatin/Paclitaxel and at least 12 cycles of bev, given together with chemotherapy and as maintenance. Only BRCAwt patients will be included in the trial. Randomization is stratified by surgery planned timepoint (neoadjuvant vs. adjuvant), surgical outcome (no residual tumor mass vs. residual tumor mass), response to chemotherapy followed by bev (CR/NED vs. PR/SD) and study center. Treatment will continue for 24 months or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoint is PFS in BRCAwt patients per RECIST v1.1. Secondary endpoints are PFS2, quality of life (EORTC QLQ-C30/OV28, FSI, SF-12, PROC-CTCAE, every day memory questionnaire), daily activity, time to next medical intervention, time to next subsequent therapy, safety assessments and OS. Clinical trial information: NCT04227522.

scholarly journals Risk Factors for GI Adverse Events in a Phase III Randomized Trial of Bevacizumab in First-Line Therapy of Advanced Ovarian Cancer: A Gynecologic Oncology Group Study

2014 ◽  
Vol 32 (12) ◽  
pp. 1210-1217 ◽  
Author(s):  
Robert A. Burger ◽  
Mark F. Brady ◽  
Michael A. Bookman ◽  
Bradley J. Monk ◽  
Joan L. Walker ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Adverse Events ◽  
Bowel Resection ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
First Line ◽  
Primary Surgery ◽  
Taxane Chemotherapy

Purpose To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Patients and Methods 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 placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage. Results Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036). Conclusion History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.

Carboplatin Plus Paclitaxel Versus Carboplatin Plus Pegylated Liposomal Doxorubicin As First-Line Treatment for Patients With Ovarian Cancer: The MITO-2 Randomized Phase III Trial

2011 ◽  
Vol 29 (27) ◽  
pp. 3628-3635 ◽  
Author(s):  
Sandro Pignata ◽  
Giovanni Scambia ◽  
Gabriella Ferrandina ◽  
Antonella Savarese ◽  
Roberto Sorio ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Group Performance ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Similar Response ◽  
First Line ◽  
Phase Iii Trial ◽  
Line Chemotherapy

Purpose Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy. Patients and Methods Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m2 or to carboplatin AUC 5 plus PLD 30 mg/m2, every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS. Results Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles. Conclusion Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.

Bevacizumab, carboplatin, and paclitaxel in the first line treatment of advanced ovarian cancer patients: the phase IV MITO-16A/MaNGO-OV2A study

2021 ◽  
pp. ijgc-2021-002434
Author(s):  
Gennaro Daniele ◽  
Francesco Raspagliesi ◽  
Giovanni Scambia ◽  
Carmela Pisano ◽  
Nicoletta Colombo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Residual Disease ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Line Treatment ◽  
First Line ◽  
Primary Surgery ◽  
First Line Treatment

ObjectiveTo explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab.MethodsA multicenter, phase IV, single arm trial was performed. Patients with advanced (FIGO (International Federation of Gynecology and Obstetrics) stage IIIB-IV) or recurrent, previously untreated, ovarian cancer received carboplatin (AUC (area under the curve) 5), paclitaxel (175 mg/m2) plus bevacizumab (15 mg/kg) on day 1 for six 3-weekly cycles followed by bevacizumab single agent (15 mg/kg) until progression or unacceptable toxicity up to a maximum of 22 total cycles. Here we report the final analysis on the role of clinical prognostic factors. The study had 80% power with a two-tailed 0.01 α error to detect a 0.60 hazard ratio with a factor expressed in at least 20% of the population. Both progression-free and overall survival were used as endpoints.ResultsFrom October 2012 to November 2014, 398 eligible patients were treated. After a median follow-up of 32.3 months (IQR 24.1–40.4), median progression-free survival was 20.8 months (95% CI 19.1 to 22.0) and median overall survival was 41.1 months (95% CI 39.1 to 43.5). Clinical factors significantly predicting progression-free and overall survival were performance status, stage, and residual disease after primary surgery. Neither baseline blood pressure/antihypertensive treatment nor the development of hypertension during bevacizumab were prognostic. There were two deaths possibly related to treatment, but no unexpected safety signal was reported.ConclusionsEfficacy and safety of bevacizumab in combination with carboplatin and paclitaxel and as maintenance were comparable to previous data. Hypertension, either at baseline or developed during treatment, was not prognostic. Performance status, stage, and residual disease after primary surgery remain the most important clinical prognostic factors.Trial registration numberEudraCT 2012-003043-29; NCT01706120.

Impact of Extended Primary Surgery on Suboptimally Operable Patients With Advanced Ovarian Cancer

2016 ◽  
Vol 26 (5) ◽  
pp. 873-883 ◽  
Author(s):  
Anton Oseledchyk ◽  
Lena Elisa Hunold ◽  
Michael R. Mallmann ◽  
Christian M. Domröse ◽  
Alina Abramian ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Advanced Ovarian Cancer ◽  
Residual Tumor ◽  
Complication Rates ◽  
Oncologic Surgery ◽  
Primary Surgery ◽  
Optimal Debulking ◽  
Upper Abdomen ◽  
Extensive Surgery

ObjectivesExtensive surgical efforts to achieve an optimal debulking (no residual tumor) in primary surgery of ovarian cancer are today’s criterion standard in gyneco-oncologic surgery. However, it is controversial whether extensive surgery, including resections of metastases in the upper abdomen and bowel resections, is justifiable in patients with not completely operable lesions.MethodsAll patients who had undergone surgery for ovarian cancer in the years 2002 to 2013 at our institution were viewed (n = 472). We retrospectively identified 278 operations for primary ovarian cancer. Ninety-six (35%) of the 278 patients showed postoperative tumor residuals and were included in this study.ResultsFifty-five (57%) of 96 patients underwent bowel resection, showing significantly higher complication rates (64% vs 39% minor complications, P = 0.017; 31% vs 9.8% severe complications, P = 0.013) compared with patients without bowel resections as well as no improvement in progression-free or overall survival (median overall survival, 19.5 vs 32.9; P = 0.382). Multiple anastomoses (≥2) were associated with higher rates for anastomotic leakage (16.7% vs 2.6%, P = 0.02) and a higher mortality (16.7% vs 0%, P = 0.04) compared with patients with only 1 anastomosis. Extensive surgery of the upper abdomen was not associated with a significant increase in complication rates.ConclusionsBecause of the increased morbidity of bowel resections without any evidence for improvement of survival, we suggest to restrain from further resection of intestines if an optimal debulking seems not feasible after removal of the major tumor bulk.

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