1279P - Cumulative exposure to bevacizumab (BV) after disease progression (PD) correlates with survival in non-small cell lung cancer (NSCLC): a time-depend...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Thomas Lynch
Authors T.J. Lynch1, M. Jahanzeb2, D.R. Spigel3, A. Wozniak4, L.F. Leon5, S. Fish5, E.D. Flick6, D. Dalal6, M. Kosty7
  • 1Comprehensive Cancer Center, Yale School Of Medicine, Yale Comprehensive Cancer Center, 06510 - New Haven/US
  • 2University Of Miami, Miller School Of Medicine, Sylvester Comprehensive Cancer Center, Deerfield Beach/US
  • 3Sarah Cannon Research Institute, US-37203 - Nashville/US
  • 4Department Of Hematology-oncology, Wayne State University, Detroit/US
  • 5Biostatistics, Genentech, Inc., 94080 - South San Francisco/US
  • 6Us Medical Affairs, Genentech, Inc., 94080 - South San Francisco/US
  • 7Department Of Oncology, Scripps Clinic, La Jolla/US

Abstract

Background

Duration of BV use appears to contribute to treatment (tx) efficacy in some cancers (eg, CRC, ovarian). A phase 3 mCRC trial met its 1° endpoint of improved postprogression overall survival (ppOS) when continuing BV with chemotherapy (CT) into 2nd-line (2L) tx. A phase 2 study showed a trend for OS benefit when adding BV to CT in BV-naive 2L NSCLC (HR 0.71; 95% CI 0.41–1.21) (Herbst JCO 2007). This analysis evaluated whether BV exposure (exp) after PD correlates with ppOS in NSCLC.

Methods

ARIES 1st-line (1L) BV-treated NSCLC patients (pts) who survived 1st PD were included. ppOS equaled the time from 1st PD to any-cause death. BV exp, over follow-up, equaled the cumulative days of BV from 1st PD. A time-dependent Cox regression model was fitted to assess the effect of cumulative BV exp on ppOS, while controlling for potential time-dependent and -fixed confounders. A landmark sensitivity analysis, also adjusting for confounders, compared ppOS in pts treated with BV beyond PD (BBP) and pts treated otherwise (No BBP) ≤30 days after PD.

Results

As of 09/2011, of 1967 enrolled 1L pts, 1461 (74%) had 1st PD. Characteristics (n = 1461) were: 48% had 1st PD within 6 mos, 52% male, 31% ≥70 y, 13% never smokers, and 13% ECOG status ≥2. The median ppOS for all pts with 1st PD was 6 mos (95% CI 5.6–6.7). Among pts with any BV tx, the mean cumulative BV exp was 116 days (range, 2–1140). Across follow-up, the HRs for ppOS decreased by ∼4% for each additional 21-day interval of cumulative exp (Table). Cumulative BV duration was associated with improved ppOS (P < .0001). The landmark analysis also showed that BBP was independently associated with higher ppOS (BBP vs No BBP; HR, 0.75; 95% CI, 0.65–0.86).

Conclusions

This analysis suggests that cumulative exp to BV after 1st PD may correspond with incremental increases in ppOS for NSCLC pts, and supports the conduct of the phase 3 AvaALL trial.

Cyclea No. of pts who received cumulative cycles of BV continuouslyb Hazard ratio (HR) for ppOS 95% confidence interval (CI)
1 229 0.959 0.941–0.978
2 159 0.920 0.885–0.956
3 118 0.883 0.833–0.935
4 84 0.847 0.784–0.914
5 72 0.812 0.738–0.894
6 55 0.779 0.694–0.874
7 41 0.747 0.653–0.855
8 32 0.717 0.614–0.836

aA cycle is calculated as 21 days of cumulative exposure after PD. bEg, n = 55 patients were continuously dosed through approximately day 126 (cycle 6) after PD.

Disclosure

T.J. Lynch: Dr. Lynch is on the Infinity Pharmaceuticals board of directors, consults for Merck, Boehringer-Ingleheim and Astex, and holds a patent on EGFR testing from Partners Healthcare.

M. Jahanzeb: Dr. Jahanzeb is a consultant/advisor for Genentech.

D.R. Spigel: Dr. Spigel is an unpaid advisor/consultant to Genentech.

A. Wozniak: Dr. Wozniak has received honoraria and research support from Genentech and research funding from Eli Lilly.

L. Leon: Dr. Leon is an employee of and holds stock options in Roche/Genentech.

S. Fish: Dr. Fish is an employee of and holds stock options in Roche/Genentech.

E.D. Flick: Dr. Flick is an employee of and holds stock options in Roche/Genentech.

D. Dalal: Dr. Dalal is an employee of and holds stock options in Roche/Genentech.

M.P. Kosty: Dr. Kosty has participated in the Genentech Speakers' Bureau.