Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial
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Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. / Pfisterer, Jacobus; Shannon, Catherine M; Baumann, Klaus; Rau, Joern; Harter, Philipp; Joly, Florence; Sehouli, Jalid; Canzler, Ulrich; Schmalfeldt, Barbara; Dean, Andrew P; Hein, Alexander; Zeimet, Alain G; Hanker, Lars C; Petit, Thierry; Marmé, Frederik; El-Balat, Ahmed; Glasspool, Rosalind; de Gregorio, Nikolaus; Mahner, Sven; Meniawy, Tarek M; Park-Simon, Tjoung-Won; Mouret-Reynier, Marie-Ange; Costan, Cristina; Meier, Werner; Reinthaller, Alexander; Goh, Jeffrey C; L'Haridon, Tifenn; Baron Hay, Sally; Kommoss, Stefan; du Bois, Andreas; Kurtz, Jean-Emmanuel; AGO-OVAR 2.21/ENGOT-ov 18 Investigators.
In: LANCET ONCOL, Vol. 21, No. 5, 05.2020, p. 699-709.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial
AU - Pfisterer, Jacobus
AU - Shannon, Catherine M
AU - Baumann, Klaus
AU - Rau, Joern
AU - Harter, Philipp
AU - Joly, Florence
AU - Sehouli, Jalid
AU - Canzler, Ulrich
AU - Schmalfeldt, Barbara
AU - Dean, Andrew P
AU - Hein, Alexander
AU - Zeimet, Alain G
AU - Hanker, Lars C
AU - Petit, Thierry
AU - Marmé, Frederik
AU - El-Balat, Ahmed
AU - Glasspool, Rosalind
AU - de Gregorio, Nikolaus
AU - Mahner, Sven
AU - Meniawy, Tarek M
AU - Park-Simon, Tjoung-Won
AU - Mouret-Reynier, Marie-Ange
AU - Costan, Cristina
AU - Meier, Werner
AU - Reinthaller, Alexander
AU - Goh, Jeffrey C
AU - L'Haridon, Tifenn
AU - Baron Hay, Sally
AU - Kommoss, Stefan
AU - du Bois, Andreas
AU - Kurtz, Jean-Emmanuel
AU - AGO-OVAR 2.21/ENGOT-ov 18 Investigators
N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.
PY - 2020/5
Y1 - 2020/5
N2 - BACKGROUND: State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab.METHODS: This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251.FINDINGS: Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin-pegylated liposomal doxorubicin-bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin-gemcitabine-bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3-21·7) in the experimental group and 11·3 months (8·0-18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7-14·2) in the experimental group versus 11·6 months (11·0-12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68-0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (<1%; large intestine perforation) and two patients in the standard group (1%; one case each of osmotic demyelination syndrome and intracranial haemorrhage).INTERPRETATION: Carboplatin-pegylated liposomal doxorubicin-bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer.FUNDING: F Hoffmann-La Roche.
AB - BACKGROUND: State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab.METHODS: This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251.FINDINGS: Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin-pegylated liposomal doxorubicin-bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin-gemcitabine-bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3-21·7) in the experimental group and 11·3 months (8·0-18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7-14·2) in the experimental group versus 11·6 months (11·0-12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68-0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (<1%; large intestine perforation) and two patients in the standard group (1%; one case each of osmotic demyelination syndrome and intracranial haemorrhage).INTERPRETATION: Carboplatin-pegylated liposomal doxorubicin-bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer.FUNDING: F Hoffmann-La Roche.
KW - Adult
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
KW - Australia/epidemiology
KW - Austria/epidemiology
KW - Bevacizumab/administration & dosage
KW - Carboplatin/administration & dosage
KW - Doxorubicin/administration & dosage
KW - Fallopian Tube Neoplasms/drug therapy
KW - Female
KW - France/epidemiology
KW - Humans
KW - Middle Aged
KW - Neoplasm Recurrence, Local/drug therapy
KW - Ovarian Neoplasms/drug therapy
KW - Paclitaxel/administration & dosage
KW - Platinum/administration & dosage
KW - Polyethylene Glycols/administration & dosage
U2 - 10.1016/S1470-2045(20)30142-X
DO - 10.1016/S1470-2045(20)30142-X
M3 - SCORING: Journal article
C2 - 32305099
VL - 21
SP - 699
EP - 709
JO - LANCET ONCOL
JF - LANCET ONCOL
SN - 1470-2045
IS - 5
ER -