Carboplatin plus paclitaxel (CP) versus carboplatin plus stealth liposomal doxorubicin (CLD) in patients with advanced ovarian cancer (AOC): Activity and safety results of the MITO-2 randomized multicenter trial

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. LBA5508-LBA5508 ◽  
Author(s):  
S. Pignata ◽  
G. Scambia ◽  
A. Savarese ◽  
R. Sorio ◽  
E. Breda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Objective Response ◽  
Haematological Toxicity ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Activity Analysis ◽  
Phase Iii ◽  
Ca 125 ◽  
First Line

LBA5508 Background: CP is standard first-line chemotherapy for AOC. MITO-2 (Multicentre Italian Trials in Ovarian Cancer) is an academic randomized phase III study testing whether CLD is more effective than CP. Methods: AOC patients (pts), stage IC-IV, aged≤75, ECOG PS≤2, were randomized to CP (C AUC5 + P 175 mg/m2,d1q21) or to CLD (C AUC5 + LD 30 mg/m2,d1q21), both for 6 cycles. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival, objective response rate (ORR), toxicity and quality of life. To have 80% power in detecting a 0.80 HR in PFS, with 2-sided α error 0.05, 632 events are needed and 820 pts were planned. Activity was evaluated according to RECIST, toxicity according to NCI-CTC. Activity analysis was not blinded and no confirmation of response was required. Results: From January 2003 to November 2007, 820 pts were randomized, 410 to each arm. Median age was 57 yrs (range 21–77). Stage III (60%) and IV (22%) were prevalent. As of March 30, 2009, with a median follow-up of 35 months, 530 events for PFS and 269 deaths have been recorded. Six cycles were received by 86% and 80% of pts, with CP and CLD respectively. With complete data for 97% of pts, 290 pts were eligible for activity analysis (≥1 target lesion). ORR was 59% with CP and 57% with CLD (p=0.70). In 182 pts with non-target lesions only, complete response was 33% with CP and 29% with CLD (p=0.64). In 168 pts with elevated CA-125 only, CA-125 normalization was obtained in 83% with CP and 86% with CLD (p=0.56). Toxicity data are complete for 97% of pts. Statistically significant differences in haematological toxicity (CP vs CLD) were: anemia all grades 59% vs 68%, grade (G) 3–4 4% vs 10%; thrombocytopenia all grades 19% vs 48%, G3–4 2% vs 16%. Statistically significant differences in non haematological toxicity were: hair loss 63% vs 14%; skin toxicity all grades 6% vs 20%, G3–4 0 vs 2%; diarrhea all grades 13% vs 6%; stomatitis all grades 9% vs 20%; neurotoxicity all grades 47% vs 15%, G3–4 3% vs 0.3%. Conclusions: CLD as first-line treatment of AOC produced a similar activity, with a different toxicity profile, compared to CP. Required events are awaited for final PFS analysis. Partially supported by Schering-Plough. No significant financial relationships to disclose.

Carboplatin plus paclitaxel versus carboplatin plus Stealth liposomal doxorubicin in patients with advanced ovarian cancer (AOC): Preliminary activity results of the MITO-2 randomized multicenter trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5532-5532 ◽  
Author(s):  
S. Pignata ◽  
G. Scambia ◽  
A. Savarese ◽  
E. Breda ◽  
R. Sorio ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Haematological Toxicity ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Multicenter Trial ◽  
Phase Iii ◽  
Ca 125 ◽  
Carboplatin Auc

5532 Background: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III study comparing the effect on progression-free survival of carboplatin/paclitaxel versus carboplatin/stealth liposomal doxorubicin (CLD) in 1st-line AOC patients. Due to the lack of published phase II data on the CLD schedule, safety and activity analyses were planned within the trial. The former, previously reported for the first 50 patients treated with CLD, showed mild haematological toxicity, while non-hematological events seldom were higher than grade 2. Methods: AOC patients with AOC (stage IC-IV), aged =75, ECOG PS =2, are randomized to CP (carboplatin AUC 5 / paclitaxel 175 mg/m2, d1q21) or to CLD (carboplatin AUC 5 + Stealth liposomal doxorubicin 30 mg/m2, d1q21), both treatments for 6 cycles. According to a phase 2 design with p0=30%, p1=50%, alfa=0.10, 50 patients with measurable target lesions as defined by RECIST criteria were required and ≥20 responses had to be observed in order to define that the experimental schedule was sufficiently active to warrant phase III continuation. Results: Out of the first 137 patients randomly assigned to CLD, 87 were not eligible for response assessment by RECIST (35 had only non target lesions; 28 had only Ca 125 increased; 23 had no lesion and normal Ca 125; 1 never started treatment). Out the 50 patients eligible for response assessment, overall 34 responses were recorded (14 complete, 20 partial) for a response rate of 68% (95% CI: 53.3–80.5). In addition, among 35 patients with all non-target lesions 9 (26%) complete responses and 18 (51%) nonCR- nonPD were observed. In the remaining 28 patients evaluable only for Ca 125, this normalized in 96% of the cases at the end of the 6 cycles. Conclusions: An a priori planned activity analysis showed that CLD every 3 weeks is feasible and active in AOC patients suboptimally debulked and with measurable lesions. The trial is ongoing; as of December 28th, 2006, 615 patients have been enrolled out of 810 planned. No significant financial relationships to disclose.

Final results of After-6 protocol 1: A phase III trial of observation versus 6 courses of paclitaxel (Pac) in advanced ovarian cancer patients in complete response (CR) after platinum-paclitaxel chemotherapy (CT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5505-5505 ◽  
Author(s):  
P. F. Conte ◽  
G. Favalli ◽  
A. Gadducci ◽  
D. Katsaros ◽  
P. L. Benedetti Panici ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Survival Rates ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Absolute Increase

5505 Background: The majority of advanced ovarian cancer patients (pts) in CR after debulking surgery and Platinum/Paclitaxel will eventually relapse. Role of maintenance CT is still questionable even if a SWOG/GOG trial has shown an improved progression free survival (PFS) with 12 vs 3 cycles of maintenance Pac. In March 1999, the After 6 Italian Cooperative Group initiated a phase III study to determine if maintenance Pac could prolong PFS in pts with a clinical (cCR) or pathological CR (pCR) after first line CT Methods: Pts with advanced ovarian cancer in cCR or pCR after 6 cycles of Platinum/Paclitaxel, were randomised to observation or 6 cycles of Pac 175 mg/sqm iv q 3 wks. Primary end point: PFS; secondary end points: overall survival (OS) and toxicities. Planned sample size: 250 pts to detect a 15% absolute increase in 2-yr PFS. Results: From 03/99 to 07/06, 200 pts were randomised. Due to the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Main patient characteristics: median age 58 yrs, median PS 0 (neurotoxicity ≥ G 2 was an exclusion criteria), stage IIb/IIc 15%, stage III 79%, stage IV 6%; 105 pts (52.5%) were in pCR. 14% of pts randomised to observation received Pac; 22% of pts randomised to Pac stopped treatment after 2–5 cycles (progression or death: 3 pts; toxicity: 9 pts; refusal: 7 pts; others: 3 pts). A G ≥ 2 neurotoxicity was reported in 25% of pts treated with Pac; other toxicities were mild. After a median follow up of 44 months, 94 pts (47%) have relapsed and 42 pts (21%) died. Median PFS were 34 and 34.5 months in observation and Pac arm respectively; 3-yr OS was 88% in observation and 78% in Pac arm. Irrespectively of treatment arm, median PFS was 34.4 months for pts with pCR and 24.5 months for those with cCR; 3-yr survival rates were 87% and 79% respectively (p=0.04). Conclusions: Six courses of maintenance Pac do not prolong PFS or OS in pts in CR after first line platinum/paclitaxel. Irrespectively of assigned treatment, the outcome of these pts is more favourable than previously reported and significantly better in the pCRs. Maintenance CT remains an experimental treatment that should be tested in pts at high risk of relapse. [Table: see text]

Phase III Trial of Carboplatin Plus Paclitaxel With or Without Gemcitabine in First-Line Treatment of Epithelial Ovarian Cancer

2010 ◽  
Vol 28 (27) ◽  
pp. 4162-4169 ◽  
Author(s):  
Andreas du Bois ◽  
Jørn Herrstedt ◽  
Anne-Claire Hardy-Bessard ◽  
Hans-Helge Müller ◽  
Philipp Harter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Objective Response ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Term Survival ◽  
Advanced Epithelial Ovarian Cancer

PurposeOne attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non–cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.Patients and MethodsWe performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m2, respectively) with the same combination and additional gemcitabine 800 mg/m2on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.ResultsBetween 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).ConclusionThe addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.

Final skin toxicity (ST) and patient-reported outcomes (PRO) results from PRIME: A randomized phase III study of panitumumab (pmab) plus FOLFOX4 (CT) for first-line metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 531-531 ◽  
Author(s):  
Jean Yves Douillard ◽  
Salvatore Siena ◽  
Josep Tabernero ◽  
Ronald L. Burkes ◽  
Mario Edmundo Barugel ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Skin Toxicity ◽  
Least Square ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Patient Reported

531^ Background: Final PRIME results showed that pmab + CT significantly improved progression-free survival (PFS) and objective response rate vs CT alone for first-line wild type (WT) KRAS mCRC. Efficacy and PRO by ST severity from the final descriptive analysis of PRIME are presented. Methods: Patients (pts) had no prior chemotherapy for mCRC, ECOG performance status ≤ 2, and tumor tissue available for biomarker testing. The final analysis occurred 30 months after the last pt was enrolled; the primary endpoint was PFS; secondary endpoints included OS, objective response, and safety. Pts who received treatment and were alive without progression at day 28 were included in the ST analysis. Results: 1183 pts were randomized. 1057 pts with WT or MT KRAS mCRC met the criteria for inclusion in the ST analysis. Maximum grade ST was observed by day 28 in > 50% of pts. Results are shown ( table ). Overall differences in change from baseline of the least square means from a mixed effects model of the EQ-5D Overall Health Rating for pmab + CT (n = 285) minus CT alone (n = 294) and for ST gr 0-1 (n = 53) minus ST gr 2-4 (n = 232) were −1.069 (95% CI: −3.6277 to 1.4896) and 0.8971 (95% CI: ‐4.0224 to 5.8167), respectively. The overall safety profile was broadly comparable across ST groups and treatment arms. Conclusions: Pts with WT KRAS mCRC receiving pmab with ST gr 2-4 had longer PFS and OS vs pts receiving CT alone. PRO were not adversely affected by ST severity. [Table: see text]

Exploratory Phase III Study of Paclitaxel and Cisplatin Versus Paclitaxel and Carboplatin in Advanced Ovarian Cancer

2000 ◽  
Vol 18 (17) ◽  
pp. 3084-3092 ◽  
Author(s):  
Jan P. Neijt ◽  
Svend A. Engelholm ◽  
Malgorzata K. Tuxen ◽  
Peter G. Sørensen ◽  
Mogens Hansen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Time ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ca 125 ◽  
Peripheral Neurotoxicity ◽  
Time Curve ◽  
Free Survival ◽  
Number Of Patients

PURPOSE: To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer. PATIENTS AND METHODS: Patients were randomly allocated to receive paclitaxel 175 mg/m2 intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m2 or carboplatin (area under the plasma concentration-time curve of 5), both on day 1. The schedule was repeated every 3 weeks for at least six cycles. Women allocated to paclitaxel-cisplatin were admitted to the hospital, whereas the carboplatin regimen was administered to outpatients. RESULTS: A total of 208 eligible patients were randomized. Both regimens could be delivered in an optimal dose and without significant delay. Paclitaxel-carboplatin produced significantly less nausea and vomiting (P < .01) and less peripheral neurotoxicity (P = .04) but more granulocytopenia and thrombocytopenia (P < .01). The overall response rate in 132 patients with measurable disease was 64% (84 of 132 patients), and in patients with elevated CA 125 levels at start, it was 74% (132 of 178 patients). With a median follow-up time of 37 months, the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months. The small number of patients entered onto the study caused wide confidence intervals (CIs) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin (hazards ratio, 1.07; 95% CI, 0.78 to 1.48) and did not allow conclusions about efficacy. CONCLUSION: Paclitaxel-carboplatin is a feasible regimen for outpatients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin.

Improving first-line therapy of advanced ovarian cancer – the AGO Ovarian Cancer Study Group perspective

2003 ◽  
Vol 13 (Suppl 2) ◽  
pp. 169-171
Author(s):  
A. Du Bois ◽  
J. Pfisterer ◽  
W. Meier ◽  
U. Wagner
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Ca 125 ◽  
Study Group ◽  
First Line ◽  
Cancer Study ◽  
First Line Therapy ◽  
Line Therapy ◽  
Cancer Study Group

This review displays the AGO Ovarian Cancer Study Group approach towards evaluation of improvement options in first-line therapy of advanced ovarian cancer. Prospectively randomized phase III trials evaluating the addition of newer drugs to standards carboplatin-paclitaxol (TC) as well as pilot trials evaluating new treatment modalities like anti-idiotype CA 125 antibodies or epidermal growth factor receptor (EGFR) modulation are presented.

Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5599-TPS5599
Author(s):  
Rebecca Christian Arend ◽  
Bradley J. Monk ◽  
Thomas J. Herzog ◽  
Jonathan A. Ledermann ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Ca 125 ◽  
Recist 1.1 ◽  
Platinum Resistant ◽  
Phase Iii Study

TPS5599 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

scholarly journals First-line PARP inhibitors in ovarian cancer: summary of an ESMO Open - Cancer Horizons round-table discussion

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e001110
Author(s):  
Susana Banerjee ◽  
Antonio Gonzalez-Martin ◽  
Philipp Harter ◽  
Domenica Lorusso ◽  
Kathleen N Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Round Table ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
European Medicines Agency ◽  
First Line ◽  
Phase Iii Trials

Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the latest breakthrough in the management of newly diagnosed advanced ovarian cancer. The results of the SOLO-1 trial in 2018 led to European Medicines Agency and Food and Drug Administration approval of olaparib as first-line maintenance therapy in patients with BRCA1/2 mutation, establishing a new standard of care. Subsequently, the results of three phase III trials (PRIMA, PAOLA-1, VELIA) evaluating the use of first-line PARP inhibitors beyond patients with BRCA1/2 mutations and as combination strategies were presented in 2019, leading to the recent approval of maintenance niraparib irrespective of biomarker status and olaparib in combination with bevacizumab in homologous recombination deficiency-positive-associated advanced ovarian cancer. An ESMO Open - Cancer Horizons round-table expert panel discussed the four phase III trials of first-line PARP inhibitor therapy and how they are changing the clinical management of advanced ovarian cancer.

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