499P - Incidence and relevance of proteinuria in bevacizumab (BV)-treated patients (pts): pooled analysis from randomized controlled trials (RCTs)

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Complications of Treatment
Presenter Richard Lafayette
Authors R. Lafayette1, B. McCall2, N.F. Li3, L. Chu4, P. Werner5, A. Das6, R.J. Glassock7
  • 1Nephrology, Stanford Glomerular Disease Center, 94305 - Stanford/US
  • 2Product Development, Oncology, Genentech, Inc., 94080 - South San Francisco/US
  • 3Biostatistics, Genentech, Inc., 94080 - South San Francisco/US
  • 4Global Product Development Biometrics, Genentech, Inc., South San Francisco/US
  • 5Statistical Programming And Analysis (spa), F. Hoffmann-La Roche AG, Basel/CH
  • 6Pdco, Genentech, Inc., South San Francisco/US
  • 7The David Geffen School Of Medicine, UCLA, 92677 - Laguna Niguel/US

Abstract

Background

Proteinuria (PU) is a recognized adverse event with BV treatment (tx); however it is not known if BV-related PU is associated with clinical outcomes. This analysis was undertaken to define the relationship between PU with BV tx and sequelae, including changes in kidney function.

Methods

A pooled safety database, comprising 22 phase 2/3 RCTs of BV across tumor types, was used to characterize PU events. Analysis pools were created based on data availability in individual studies. Raw and time-adjusted PU rates and data on the association between PU and arterial thromboembolic events (TEs), venous TEs, and infection were derived from Pool 1 (17 RCTs; n = 14,548). Data from Pool 2 (8 RCTs; n = 9,158) were used to estimate the association between lab-reported PU and changes in kidney function based on serum creatinine (sCr) levels. Severity of kidney function change was categorized using the RIFLE classification for acute kidney injury (AKI). Potential predictors of PU were also assessed.

Results

In Pool 1, the incidence rate of any-grade (gr) PU was 8.2% (733/8917) and 4.6% (257/5631) in BV and control pts, respectively; gr ≥3 PU occurred in 1.4% and 0.2%, respectively. Pts developing PU had a numerically increased rate of any-gr infection irrespective of tx (driven mostly by urinary tract infection); however, no association was found between PU and TEs (arterial or venous). In Pool 2, PU gr and tx appeared to slightly shift the rate of post-baseline AKI (Table). Evaluated risk factors (age, sex, history of hypertension or diabetes) were not found to be significantly predictive for gr ≥3 PU.

Conclusions

The use of laboratory events and pooled data confirm a modest increase in PU with BV tx. The development of PU in BV-treated pts was associated with a modest increase in the risk of infection, but not TEs, and a trend toward a decrease in kidney function. Whether these associations are causal cannot be determined by this analysis.

Tx group Worst post-BL gr of PUa Pts without PU at BL, n Worst post-BL kidney function (RIFLE classification), n (%)
Normal Riskb Injuryc Failured
BV (n = 5098) 0 2960 2277 (76.9) 585 (19.8) 66 (2.2) 25 (0.8)
1 1381 1021 (73.9) 307 (22.2) 31 (2.2) 20 (1.4)
2 562 391 (69.6) 137 (24.4) 18 (3.2) 14 (2.5)
3 59 34 (57.6) 19 (32.2) 4 (6.8) 2 (3.4)
No BV (n = 3186) 0 2144 1736 (81.0) 349 (16.3) 39 (1.8) 18 (0.8)
1 769 618 (80.4) 123 (16.0) 19 (2.5) 9 (1.2)
2 166 124 (74.7) 32 (19.3) 7 (4.2) 3 (1.8)
3 2 1 (50.0) 1 (50.0)

aCTCAE grade. No patients had gr 4 PU.

bIncreased sCR ×1.5 or estimated creatinine clearance (eCrCl) decrease >25%.

cIncreased sCr ×2 or eCrCl decrease >50%.

dIncreased sCr ×3, eCrCl decrease >75% or sCr ≥4 mg/dL.

Note: missing values for each row are not shown.

BL, baseline.

Disclosure

B. McCall: Dr. McCall is an employee of and holds stock options in Genentech, Inc.

N.F. Li: Dr. Li is an employee of and holds stock options in Genentech, Inc.

L. Chu: Ms. Chu is an employee of and holds stock options in Genentech, Inc.

P. Werner: Dr. Werner is an employee of F. Hoffmann-La Roche Ltd.

A. Das: Dr. Das is an employee of and holds stock options in Genentech, Inc.

R.J. Glassock: Dr. Glassock is a consultant to Genentech.

All other authors have declared no conflicts of interest.