1278P - Cumulative exposure (EXP) to bevacizumab (BV) maintenance after induction therapy and survival in advanced non-small cell lung cancer (NSCLC): a tim...

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 Nicholas Thatcher
Authors N. Thatcher1, P. Garrido Lopez2, N. Pavlakis3, J. Laskin4, E. Dansin5, F. Griesinger6, L.F. Leon7, D. Dalal8, P. Perez-Moreno9, L. Crinò10
  • 1Medical Oncology, University of Manchester, M20 4BX - Manchester/UK
  • 2Hospital Ramon y Cajal, ES-28034 - Madrid/ES
  • 3Medical Oncology, Royal North Shore Hospital, AU-2065 - St Leonards/AU
  • 4Medical Oncology, BC Cancer Agency, Vancouver/CA
  • 5Département De Cancérologie Générale, CLCC Oscar Lambret, Lille Cedex/FR
  • 6Klinik Für Hämatologie Und Onkologie, Pius-Hospital Oldenburg, Oldenburg/DE
  • 7Biostatistics, Genentech, Inc., 94080 - South San Francisco/US
  • 8Us Medical Affairs, Genentech, Inc., 94080 - South San Francisco/US
  • 9Pharmaceuticals Division, Gpsmo, F. Hoffmann-La Roche Ltd, Basel/CH
  • 10Department Of Oncology, Hospital Santa Maria della Misericordia, 06100 - Perugia/IT

Abstract

Background

Exploratory analyses from randomized and observational studies have shown that continuation BV until progressive disease (PD) is associated with prolonged overall survival (OS) in advanced NSCLC. We evaluated the correlation between cumulative exp to post-induction phase (post-IP) BV and OS in patients (pts) with NSCLC.

Methods

The multinational phase 4 SAiL study enrolled advanced NSCLC pts receiving BV with 1st-line chemotherapy (CT). Pts who began BV and CT simultaneously and did not have PD after completing 12–18 weeks (4–6 cycles) of CT were included for analysis. OS was measured from the end of each pt's BV + CT IP. BV exp, over follow-up, was defined as the cumulative days of post-IP BV treatment (tx). A time-dependent Cox regression model was fitted to assess the effect of cumulative post-IP BV exp on OS, while controlling for potential time-dependent and -fixed confounders. A landmark sensitivity analysis compared OS in pts in the analysis population who did and did not continue BV after IP.

Results

Of 2212 pts in SAiL, 1625 NSCLC pts were alive and without PD through IP tx. Baseline characteristics (n = 1625) were: 58% male, 13% ≥70 y, 32% never smokers, and 4% ECOG PS ≥2. 1047 (64%) pts received post-IP BV. Baseline and end-of-IP characteristics were generally similar between pts receiving post-IP BV or no post-IP BV within the landmark period. Across follow-up, the hazard ratios (HRs) for OS decreased by ∼7% (range, 5%–9%) with each additional 21-day interval of cumulative exp (Table). Landmark sensitivity analyses also support that post-IP BV was associated with longer OS (post-IP BV vs no post-IP BV; HR, 0.74; 95% CI, 0.64–0.85).

Conclusions

These data from SAiL along with previously presented data from ARIES suggest that cumulative exp to post-IP BV is associated with incremental increases in OS for NSCLC pts.

Cumulative post-IP BV cyclesa No. of pts who received cumulative cycles of post-IP BV continuouslyb HR (95% confidence interval) for OS
1 1006 0.91 (0.89–0.93)
2 884 0.82 (0.79–0.86)
3 758 0.75 (0.70–0.80)
4 643 0.68 (0.62–0.74)
5 530 0.62 (0.55–0.69)
6 447 0.56 (0.49–0.64)
7 370 0.51 (0.44–0.59)
8 315 0.46 (0.39–0.55)

a A cycle is approximately 21 days of post-IP cumulative exp. bEg, n = 530 pts were continuously dosed through day 105 (cycle 5) after IP.

Disclosure

N. Thatcher: Dr. Thatcher is a member of the Roche advisory board and has received speaker fees from Roche.

P. Garrido Lopez: Dr. Garrido Lopez is a member of the Roche advisory board.

N. Pavlakis: Dr. Pavlakis has received speaker honoraria and travel grants from Roche, and has participated in Roche Advisory Boards.

J. Laskin: Dr. Laskin is a member of the Canadian National Ad Board for lung cancer for Astra Zeneca, BI, and Eli Lilly and has received research funding from Roche, Boehringer-Ingelheim, and Eli Lilly.

E. Dansin: Dr. Dansin is a member of the Roche advisory board.

F. Griesinger: Dr. Griesinger is a member of national and international advisory boards of Roche and has received honoraria for presentations at meetings.

L. Leon: Dr. Leon 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.

P. Perez-Moreno: Dr. Perez-Moreno is an employee of and holds stock options in F. Hoffman LaRoche.

L. Crino: Dr. Crino received honorarium from Roche as a speaker in a scientific symposium.