Trial-level analysis of progression-free survival and response rate as end points of trials of first-line chemotherapy in advanced ovarian cancer

2017 ◽  
Vol 34 (5) ◽  
Author(s):  
Giuseppe Colloca ◽  
Antonella Venturino
Keyword(s):  
Ovarian Cancer ◽  
Response Rate ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
End Points ◽  
Free Survival ◽  
Level Analysis ◽  
Line Chemotherapy

Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

2014 ◽  
Vol 32 (30) ◽  
pp. 3374-3382 ◽  
Author(s):  
Andreas du Bois ◽  
Anne Floquet ◽  
Jae-Weon Kim ◽  
Joern Rau ◽  
Josep M. del Campo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Growth Factor Receptor ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Line Chemotherapy

PurposePazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Patients and MethodsNine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.ResultsMaintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).ConclusionPazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).

Docetaxel and Cisplatin in Combination as First-Line Chemotherapy for Advanced Epithelial Ovarian Cancer

1999 ◽  
Vol 17 (7) ◽  
pp. 2069-2069 ◽  
Author(s):  
P. A. Vasey ◽  
J. Paul ◽  
A. Birt ◽  
E. J. Junor ◽  
N. S. Reed ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Fluid Retention ◽  
Ca 125 ◽  
Severe Neutropenia ◽  
First Line ◽  
Free Survival ◽  
Line Chemotherapy

PURPOSE: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m2 and docetaxel 75 mg/m2); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m2 and docetaxel 85 mg/m2). RESULTS: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION: Cisplatin and docetaxel can be administered at doses of 75 mg/m2 and 75 mg/m2, respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m2 adds unacceptable hematologic toxicity and potential risks to the patient.

scholarly journals Estimating long-term overall survival with olaparib as maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations

2021 ◽  
Vol 17 (3) ◽  
pp. 97-105
Author(s):  
N. A. Avxentyev ◽  
S. V. Khokhlova ◽  
M. Yu. Frolov ◽  
A. S. Makarov
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
First Line ◽  
Brca Mutations ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Line Chemotherapy

Background. According to randomized clinical trial SOLO1 olaparib statistically significantly improves progression-free survival versus placebo as a maintenance monotherapy in patients aged 18 and over with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy. As the data on overall survival (OS) in this trial remains interim it is still uncertain whether treatment with olaparib can provide any benefits in terms of OS.Objective: to evaluate a long-term OS for olaparib versus placebo as a maintenance monotherapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy.Materials and methods. A 10-year mathematic model of disease progression and survival on olaparib versus placebo was developed. Modelling was based on data on progression-free survival from SOLO1 trial and data on OS after platinum-sensitive and platinum-resistant relapses from OCEANS and AURELIA trials. Additionally, patients who haven’t been treated with olaparib after first-line therapy in base-case scenario were assumed to get olaparib as a second-line treatment after platinum-sensitive relapse; mortality modelling for these patients was based on data from SOLO2 trial.Results. Median OS for olaparib was 107 months versus 66 months for placebo. 46 % of patients treated with olaparib were alive by the end of 10-year modelling period, but only 28 % patients from the placebo group. Hazard ratio of death for olaparib versus placebo was 0.64 (95 % confidence interval 0.49–0.84). Probabilistic sensitivity analysis showed robustness of these results.Conclusion. Using olaparib as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response on first line chemotherapy, statistically significantly reduces risk of death by 36 %, compared to placebo.

scholarly journals The Efficacy of Ramucirumab in the Treatment of Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis of RCTs

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hongqiong Yang ◽  
Yaojun Zhou ◽  
Liangzhi Wang ◽  
Tianyi Gu ◽  
Mengjia Lv ◽  
...  
Keyword(s):  
Response Rate ◽  
Meta Analysis ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer ◽  
Line Chemotherapy

Five electronic databases were searched for eligible records. Outcomes were presented and analyzed according to the objective response rate (ORR), progression-free survival (PFS) rate, and overall survival (OS) rate. Five records involving 2,024 participants were included in the study. The pooled analysis of OS and PFS were longer with ramucirumab (RAM) therapy than without RAM for OS (odds ratio OR = 0.90 , 95% confidence interval CI = 0.82 – 1.00 , p = 0.05 ) and PFS ( OR = 0.74 , 95 % CI = 0.57 – 0.96 , p = 0.02 ). Moreover, compared with the current first-line chemotherapy, the OS ( OR = 0.93 , 95 % CI = 0.83 – 1.04 , p = 0.19 ) and PFS ( OR = 0.82 , 95 % CI = 0.64 – 1.06 , p = 0.13 ) results were not significantly higher with RAM. The ORRs of the patients in the RAM therapy groups were significantly higher than those in the groups without RAM ( OR = 1.40 , 95 % CI = 1.14 – 1.73 , p = 0.001 ).

Poly-(ADP-ribose) polymerase inhibitors: paradigm shift in the first-line treatment of newly diagnosed advanced ovarian cancer

2020 ◽  
Vol 21 (10) ◽  
pp. 721-727
Author(s):  
Fady Gh Haddad ◽  
Elias Karam ◽  
Elissar Moujaess ◽  
Hampig Raphael Kourie
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Excision Repair ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
First Line ◽  
Free Survival ◽  
Base Excision ◽  
Breast Cancer Gene

Debulking surgery associated with chemotherapy represent the backbone of ovarian cancer therapy. Adding bevacizumab has improved survival. Recently, PARP inhibitors were added in the first line as maintenance treatment for the patients who achieve a complete or partial response. These drugs act by blocking the activity of the PARP enzyme responsible for base-excision repair, and have shown positive responses when used for tumors lacking homologous recombination. Olaparib, niraparib and veliparib were evaluated and showed an increase in the duration of progression-free survival: 22.1 months (hazard ratio [HR] = 0.59), 13.8 (HR = 0.62) and 23.5 (HR = 0.68) with olaparib, niraparib and veliparib, respectively. This review describes the benefit of PARP inhibitors as maintenance therapy and discusses the efficacy according to breast cancer gene and homologous recombination status.

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]

Phase III Trial of High-Dose Sequential Chemotherapy With Peripheral Blood Stem Cell Support Compared With Standard Dose Chemotherapy for First-Line Treatment of Advanced Ovarian Cancer: Intergroup Trial of the AGO-Ovar/AIO and EBMT

2007 ◽  
Vol 25 (27) ◽  
pp. 4187-4193 ◽  
Author(s):  
Volker Möbus ◽  
Hannes Wandt ◽  
Norbert Frickhofen ◽  
Carmelo Bengala ◽  
Kim Champion ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peripheral Blood Stem Cell ◽  
Standard Dose ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
High Dose ◽  
First Line ◽  
Sequential Chemotherapy ◽  
Free Survival ◽  
First Line Treatment

PurposeAlthough ovarian cancer is one of the most chemotherapy-sensitive solid tumors, cure after radical surgery and chemotherapy is uncommon. A randomized trial comparing high-dose sequential chemotherapy with peripheral blood stem cell (PBSC) support with platinum-based combination chemotherapy was conducted to investigate whether dose-intensification improves outcome.Patients and MethodsOne hundred forty-nine patients with untreated ovarian cancer were randomly assigned after debulking surgery to receive standard combination chemotherapy or sequential high-dose (HD) treatment with two cycles of cyclophosphamide and paclitaxel followed by three cycles of HD carboplatin and paclitaxel with PBSC support. HD melphalan was added to the final cycle. The median age was 50 years (range, 20 to 65 years) and International Federation of Gynecology and Obstetrics stage was IIb/IIc in 4%, III in 78%, and IV in 17%.ResultsSeventy-six percent of patients received all five cycles in the HD arm and the main toxicities were neuro-/ototoxicity, gastrointestinal toxicity, and infection and one death from hemorrhagic shock. After a median follow-up of 38 months, the progression-free survival was 20.5 months in the standard arm and 29.6 months in the HD arm (hazard ratio [HR], 0.84; 95% CI, 0.56 to 1.26; P, .40). Median overall survival (OS) was 62.8 months in the standard arm and 54.4 months in the HD arm (HR, 1.17; 95% CI, 0.71 to 1.94; P, .54).ConclusionThis is the first randomized trial comparing sequential HD versus standard dose chemotherapy in first-line treatment of patients with advanced ovarian cancer. We observed no statistically significant difference in progression-free survival or OS and conclude that HD chemotherapy does not appear to be superior to conventional dose chemotherapy.

Đánh giá kết quả hóa trị triệu chứng bước 1 ở bệnh nhân ung thư dạ dày giai đoạn tiến xa bằng phác đồ có epirubicin, oxaliplatin, capecitabin

2020 ◽  
Author(s):  
Hong Chuyen Nguyen Thi
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Response Rate ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
First Line ◽  
Free Survival ◽  
Gastric Cancer Patients ◽  
Line Chemotherapy

Purpose:to study clinical and subclinical characteristics in advanced stage gastric cancer patients and to evaluate response rate, overall survival, progression free survival and toxicities on advanced stage gastric cancer patients treated with first line chemotherapy using epirubicin, oxaliplatin, capecitabin Methods: A retrospective case series study with 134 advanced stage gastric cancer patients on first line chemotherapy using epirubicin, oxaliplatin, capecitabin recruited from oncology department, the Hospital of Hue University of Medicine and Pharmacy and Cancer Center at Hue Central Hospital during January 2015 to June 2019. Results: Patient’s mean age was 54,9; men/women was 2,52/1. The most frequent clinical symptom reported was epigastric pain 81,3%. KPS 80-90% presented in almost patient (93.3%). The most common site of cancer was pyloric antrum (61,9%). 58,2% patients had distant metastasis disease which liver was the most frequent site. The overall response rate, partial response rate, complete response rate were 49,2%, 42,5%, 6,7% respectively. The median progression free survival was 8,6 ± 0,15 months and the overall survival was 10,7 ± 1,1 months. The pathologic type and combined salvage surgery status were response correlated factors. Grade 3, 4 toxicities in term of hematology, liver and kidney function were only exhibited in a few cases. Patients were tolerated well with chemotherapy. No deaths related to chemotherapy. Conclusions: This study shows that EOX regimen was safe and effective. As a results, we can apply this for first line pallative chemotherapy on advanced stage gastric cancer which KPS ≥70%.

Sign in / Sign up

Export Citation Format

Share Document