bevacizumab
Sources réglementaires consultées
Indications approuvées
- Cancer colorectal métastatique, en association à une chimiothérapie intraveineuse à base de fluoropyrimidines ; non indiqué en adjuvant.
- Cancer bronchique non à petites cellules non épidermoïde non résécable, localement avancé, récidivant ou métastatique en première ligne, avec carboplatine et paclitaxel.
- Glioblastome récidivant chez l’adulte.
- Carcinome rénal métastatique avec interféron alfa.
- Cancer du col utérin persistant, récidivant ou métastatique avec paclitaxel et cisplatine ou paclitaxel et topotécan.
- Cancer épithélial avancé ou récidivant de l’ovaire, de la trompe de Fallope ou cancer péritonéal primitif selon le protocole avec carboplatine/paclitaxel, carboplatine/gemcitabine ou traitement de la maladie résistante au platine.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer une perforation gastro-intestinale ou des fistules sévères ou mortelles. Arrêter définitivement en cas de perforation, fistule trachéo-œsophagienne, fistule de grade 4 ou fistule touchant un organe interne. Dans le cancer de l’ovaire, éviter MVASI en cas d’atteinte rectosigmoïdienne ou intestinale ou de symptômes d’occlusion intestinale. — OpenFDA, MVASI bevacizumab-awwb set_id 0a562b4e-67ce-4bab-852c-d9ee71e55fb8, spl_id ea079b8e-24b7-4e03-8340-8078f30f6d98
- Mise en garde majeure · Il peut provoquer une hémorragie sévère ou mortelle, dont une hémoptysie. Arrêter en cas d’hémorragie de grade 3–4 et ne pas administrer en cas d’hémoptysie récente d’au moins 2,5 ml de sang rouge. — OpenFDA, MVASI bevacizumab-awwb set_id 0a562b4e-67ce-4bab-852c-d9ee71e55fb8, spl_id ea079b8e-24b7-4e03-8340-8078f30f6d98
- Mise en garde majeure · Il augmente les événements thromboemboliques artériels et veineux. Arrêter en cas d’événement artériel sévère ou de thromboembolie veineuse de grade 4. — OpenFDA, MVASI bevacizumab-awwb set_id 0a562b4e-67ce-4bab-852c-d9ee71e55fb8, spl_id ea079b8e-24b7-4e03-8340-8078f30f6d98
- Mise en garde majeure · Chez les patients de 65 ans ou plus, le risque de thromboembolie artérielle était accru ; évaluer soigneusement les facteurs de risque et surveiller les signes et symptômes. — OpenFDA, MVASI bevacizumab-awwb set_id 0a562b4e-67ce-4bab-852c-d9ee71e55fb8, spl_id ea079b8e-24b7-4e03-8340-8078f30f6d98
- Mise en garde majeure · Il peut provoquer hypertension sévère, PRES, protéinurie, syndrome néphrotique, insuffisance cardiaque et réactions à la perfusion. Surveiller la pression artérielle et la protéinurie ; suspendre en cas d’hypertension sévère non contrôlée ou de protéinurie ≥2 g/24 h, et arrêter en cas de crise hypertensive, encéphalopathie, PRES, syndrome néphrotique, insuffisance cardiaque ou réaction sévère à la perfusion. — OpenFDA, MVASI bevacizumab-awwb set_id 0a562b4e-67ce-4bab-852c-d9ee71e55fb8, spl_id ea079b8e-24b7-4e03-8340-8078f30f6d98
- Mise en garde majeure · Il peut provoquer une insuffisance ovarienne et altérer la fertilité. Informer avant le traitement et envisager la préservation de la fertilité. — OpenFDA, MVASI bevacizumab-awwb set_id 0a562b4e-67ce-4bab-852c-d9ee71e55fb8, spl_id ea079b8e-24b7-4e03-8340-8078f30f6d98
Effets indésirables
Communs (≥1%)
épistaxis · hypertension · céphalées · protéinurie · rhinite · altération du goût · sécheresse cutanée · douleur dorsale
Rares mais graves
perforation gastro-intestinale · hémorragie mortelle · événement thromboembolique artériel · crise hypertensive ou PRES · syndrome néphrotique · insuffisance cardiaque · complication sévère de cicatrisation
Grossesse et allaitement
Il peut provoquer une toxicité embryofœtale. Utiliser une contraception efficace pendant le traitement et pendant 6 mois après la dernière dose. Ne pas allaiter pendant le traitement ni pendant 6 mois après. Il peut provoquer une insuffisance ovarienne et altérer la fertilité.
Bibliographie récente (PubMed)
IMbrave150 demonstrated that atezolizumab plus bevacizumab led to significantly improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib in patients with unresectable hepatocellular carcinoma at the primary analysis (after a median 8.6 months of follow-up). We present updated data after 12 months of additional follow-up. Patients with systemic treatment-naive, unresectable hepatocellular carcinoma were randomized 2:1 to receive 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily in this open-label, phase III study. Co-primary endpoints were OS and PFS by independently assessed RECIST 1.1 in the intention-to-treat population. Secondary efficacy endpoints included objective response rates and exploratory subgroup efficacy analyses. This is a post hoc updated analysis of efficacy and safety. From March 15, 2018, to January 30, 2019, 501 patients (intention-to-treat population) were randomly allocated to receive atezolizumab plus bevacizumab (n = 336) or sorafenib (n = 165). On August 31, 2020, after a median 15.6 (range, 0-28.6) months of follow-up, the median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab plus bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR] 0.66; 95% CI 0.52-0.85; descriptive p <0.001). The median PFS was 6.9 (95% CI 5.7-8.6) and 4.3 (95% CI 4.0-5.6) months in the respective treatment groups (HR 0.65; 95% CI 0.53-0.81; descriptive p < 0.001). Treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 and 72 (46%) of 156 safety-evaluable patients in the respective groups, and treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. After longer follow-up, atezolizumab plus bevacizumab maintained clinically meaningful survival benefits over sorafenib and had a safety profile consistent with the primary analysis. NCT03434379. The primary analysis of IMbrave150 showed that atezolizumab plu
For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined. To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer. Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022). Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days. The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate. In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74
In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high
No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098. The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group,
Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival. In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries. Eligible patients were randomly assigned (1:1:1), stratified by TACE method, region, and portal vein invasion, using an interactive voice response or web response system, to TACE plus either durvalumab plus bevacizumab (1500 mg intravenous durvalumab once every 4 weeks, then 1120 mg durvalumab plus 15 mg/kg intravenous bevacizumab once every 3 weeks), durvalumab plus placebo (same regimen using placebo instead of bevacizumab), or placebo alone (same regimen using placebo instead of durvalumab and instead of bevacizumab). Participants, investigators, and those assessing outcomes were masked to treatment assignment until data analysis. The primary endpoint was progression-free survival, by blinded independent central review (BICR), and per RECIST version 1.1, with durvalumab plus bevacizumab versus placebo alone in the intention-to-treat population (ITT; ie, all participants assigned to treatment). Key secondary endpoints were progression-free survival by BICR per RECIST version 1.1 with durvalumab plus placebo versus placebo alone, overall survival, and time to deterioration in select patient-reported outcomes. Participants continue to