Data clearly demonstrates bevacizumab’s inferiority for DME

June 7, 2017

All three anti-vascular endothelial growth factor (anti-VEGF) agents that are commercially available have demonstrated efficacy for the treatment of diabetic macular edema (DME). However, it is clear from the results of clinical trials that outcomes with bevacizumab are not as good as those obtained using ranibizumab or aflibercept, according to Jean-François Korobelnik, MD.

Reviewed by Jean-François Korobelnik, MD

Dr. KorobelnikAll three anti-vascular endothelial growth factor (anti-VEGF) agents that are commercially available have demonstrated efficacy for the treatment of diabetic macular edema (DME). However, it is clear from the results of clinical trials that outcomes with bevacizumab are not as good as those obtained using ranibizumab or aflibercept, according to Jean-François Korobelnik, MD. 

Read the other side of the debate: Access, costs of bevacizumab key factors for DME therapy

Providing the con position in the debate, “Bevacizumab is as Good as Ranibizumab and Aflibercept for DME,” Dr. Korobelnik reported that the Diabetic Retinopathy Clinical Research Network (DRCRnet) Protocol T randomized 660 adults with center-involving DME and baseline ETDRS visual acuity of 78 to 24 letters (Snellen equivalent ~20/32 to ~20/320) to intravitreal injection with aflibercept 2.0 mg (Eylea, Regeneron), bevacizumab 1.25 mg (Avastin, Genentech), or ranibizumab 0.3 mg (Lucentis, Genentech).

Dr. Korobelnik is professor and chairman, department of ophthalmology, University Hospital of Bordeaux, France.

Repeat injections were administered as needed, as often as every 4 weeks according to the protocol-specified algorithm, he added. Eyes with residual edema at 6 months were treated with focal laser unless the investigator felt it was unsafe.

About half of the population had baseline visual acuity worse than 20/40. In that cohort, analyses of data from the 1-year visit showed statistically significant greater improvement from baseline visual acuity for eyes treated with aflibercept compared with the bevacizumab and ranibizumab groups.

The mean visual acuity gain with aflibercept was about 19 letters compared with 13 letters for ranibizumab and 12 letters in the bevacizumab group, he added.'

 

Same pattern found

Analyses of mean change in optical coherence tomography (OCT) central subfield thickness (CST) showed the same pattern in terms of aflibercept providing the greatest improvement from baseline (-210 µm), followed by ranibizumab (-176 µm) and with bevacizumab being associated with the least amount of change (-135 µm).

In pairwise comparisons, there was no statistically significant difference between aflibercept and ranibizumab, but both agents were significantly superior to bevacizumab for drying the macula.

When data from the 2-year visit were analyzed, aflibercept maintained its numerical superiority for greater improvement from baseline visual acuity compared with ranibizumab and bevacizumab in the cohort of eyes with baseline visual acuity worse than 20/40 (+18.3 versus +16.1 and +13.3 letters, respectively). The difference between aflibercept and bevacizumab remained statistically significant, but there was no significant difference comparing aflibercept with ranibizumab or ranibizumab with bevacizumab.

Again, aflibercept had the best drying effect on the macula-mean change from baseline CST in the aflibercept, ranibizumab, and bevacizumab groups was -211 µm, -174 µm, and -185 µm, respectively, and the difference between aflibercept and bevacizumab remained statistically significant.

Post hoc data

A subsequently published report of additional efficacy post hoc analyses of data from Protocol T presented results from an evaluation of change in visual acuity area under the curve (AUC). It also showed statistically significant differences favoring aflibercept over both ranibizumab and bevacizumab.

For patients with baseline visual acuity worse than 20/40, the mean change in visual acuity over 2 years (AUC) was +17.1 letters for aflibercept, +13.6 letters for ranibizumab, and +12.1 letters in the bevacizumab group.

Further highlighting the difference in functional outcomes between groups, Dr. Korobelnik offered graphical depictions of the AUC data.

“Comparing aflibercept and bevacizumab, a difference between treatments is seen already after two injections,” Dr. Korobelnik said. “The benefit of aflibercept over bevacizumab is maintained until 2 years! I ask, which treatment would you prefer?”

Read the other side of the debate: Access, costs of bevacizumab key factors for DME therapy

 

Jean-François Korobelnik, MD

E: jean-francois.korobelnik@chu-bordeaux.fr

This article was adapted from a presentation that Jean-François Korobelnik, MD, delivered at the 2017 World Retina Congress. Dr. Korobelnik is a consultant to and investigator for Bayer, Novartis, and Roche.