A phase 3 trial of bevacizumab in ovarian cancer

TY - JOUR

T1 - A phase 3 trial of bevacizumab in ovarian cancer

AU - Perren, Timothy J

AU - Swart, Ann Marie

AU - Pfisterer, Jacobus

AU - Ledermann, Jonathan A

AU - Pujade-Lauraine, Eric

AU - Kristensen, Gunnar

AU - Carey, Mark S

AU - Beale, Philip

AU - Cervantes, Andrés

AU - Kurzeder, Christian

AU - du Bois, Andreas

AU - Sehouli, Jalid

AU - Kimmig, Rainer

AU - Stähle, Anne

AU - Collinson, Fiona

AU - Essapen, Sharadah

AU - Gourley, Charlie

AU - Lortholary, Alain

AU - Selle, Frédéric

AU - Mirza, Mansoor R

AU - Leminen, Arto

AU - Plante, Marie

AU - Stark, Dan

AU - Qian, Wendi

AU - Parmar, Mahesh K B

AU - Oza, Amit M

AU - ICON7 Investigators

AU - Mahner, Sven

PY - 2011/12/29

Y1 - 2011/12/29

N2 - BACKGROUND: Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease.METHODS: We randomly assigned women with ovarian cancer to carboplatin (area under the curve, 5 or 6) and paclitaxel (175 mg per square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (7.5 mg per kilogram of body weight), given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until progression of disease. Outcome measures included progression-free survival, first analyzed per protocol and then updated, and interim overall survival.RESULTS: A total of 1528 women from 11 countries were randomly assigned to one of the two treatment regimens. Their median age was 57 years; 90% had epithelial ovarian cancer, 69% had a serous histologic type, 9% had high-risk early-stage disease, 30% were at high risk for progression, and 70% had stage IIIC or IV ovarian cancer. Progression-free survival (restricted mean) at 36 months was 20.3 months with standard therapy, as compared with 21.8 months with standard therapy plus bevacizumab (hazard ratio for progression or death with bevacizumab added, 0.81; 95% confidence interval, 0.70 to 0.94; P=0.004 by the log-rank test). Nonproportional hazards were detected (i.e., the treatment effect was not consistent over time on the hazard function scale) (P<0.001), with a maximum effect at 12 months, coinciding with the end of planned bevacizumab treatment and diminishing by 24 months. Bevacizumab was associated with more toxic effects (most often hypertension of grade 2 or higher) (18%, vs. 2% with chemotherapy alone). In the updated analyses, progression-free survival (restricted mean) at 42 months was 22.4 months without bevacizumab versus 24.1 months with bevacizumab (P=0.04 by log-rank test); in patients at high risk for progression, the benefit was greater with bevacizumab than without it, with progression-free survival (restricted mean) at 42 months of 14.5 months with standard therapy alone and 18.1 months with bevacizumab added, with respective median overall survival of 28.8 and 36.6 months.CONCLUSIONS: Bevacizumab improved progression-free survival in women with ovarian cancer. The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression. (Funded by Roche and others; ICON7 Controlled-Trials.com number, ISRCTN91273375.).

AB - BACKGROUND: Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease.METHODS: We randomly assigned women with ovarian cancer to carboplatin (area under the curve, 5 or 6) and paclitaxel (175 mg per square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (7.5 mg per kilogram of body weight), given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until progression of disease. Outcome measures included progression-free survival, first analyzed per protocol and then updated, and interim overall survival.RESULTS: A total of 1528 women from 11 countries were randomly assigned to one of the two treatment regimens. Their median age was 57 years; 90% had epithelial ovarian cancer, 69% had a serous histologic type, 9% had high-risk early-stage disease, 30% were at high risk for progression, and 70% had stage IIIC or IV ovarian cancer. Progression-free survival (restricted mean) at 36 months was 20.3 months with standard therapy, as compared with 21.8 months with standard therapy plus bevacizumab (hazard ratio for progression or death with bevacizumab added, 0.81; 95% confidence interval, 0.70 to 0.94; P=0.004 by the log-rank test). Nonproportional hazards were detected (i.e., the treatment effect was not consistent over time on the hazard function scale) (P<0.001), with a maximum effect at 12 months, coinciding with the end of planned bevacizumab treatment and diminishing by 24 months. Bevacizumab was associated with more toxic effects (most often hypertension of grade 2 or higher) (18%, vs. 2% with chemotherapy alone). In the updated analyses, progression-free survival (restricted mean) at 42 months was 22.4 months without bevacizumab versus 24.1 months with bevacizumab (P=0.04 by log-rank test); in patients at high risk for progression, the benefit was greater with bevacizumab than without it, with progression-free survival (restricted mean) at 42 months of 14.5 months with standard therapy alone and 18.1 months with bevacizumab added, with respective median overall survival of 28.8 and 36.6 months.CONCLUSIONS: Bevacizumab improved progression-free survival in women with ovarian cancer. The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression. (Funded by Roche and others; ICON7 Controlled-Trials.com number, ISRCTN91273375.).

KW - Angiogenesis Inhibitors

KW - Antibodies, Monoclonal, Humanized

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Carboplatin

KW - Combined Modality Therapy

KW - Disease-Free Survival

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Middle Aged

KW - Neoplasms, Glandular and Epithelial

KW - Ovarian Neoplasms

KW - Paclitaxel

KW - Quality of Life

KW - Survival Analysis

U2 - 10.1056/NEJMoa1103799

DO - 10.1056/NEJMoa1103799

M3 - SCORING: Journal article

C2 - 22204725

VL - 365

SP - 2484

EP - 2496

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 26

ER -