1271P - Analysis of PFS and OS from the SATURN study according to EGFR IHC status using the H-score reading method
|Date||29 September 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation I|
Non-Small-Cell Lung Cancer, Metastatic
J. Mazières1, W. Brugger2, F. Cappuzzo3, P. Middel4, A. Frosch5, I. Bara6, G. Klingelschmitt7, B. Klughammer8
In the phase III SATURN study, maintenance erlotinib significantly prolonged progression-free survival (PFS) vs placebo in patients (pts) with advanced non-small-cell lung cancer (NSCLC) and non-progressive disease after first-line chemotherapy (Cappuzzo et al, Lancet Oncol 2010). Epidermal growth factor receptor (EGFR) expression analysis by immunohistochemistry (IHC) found no significant difference in PFS (p = 0.63) or overall survival (OS; p = 0.52) with erlotinib by EGFR IHC status (Brugger et al, J Clin Oncol 2011). Recently, Pirker at al. (Lancet Oncol 2012) presented data on EGFR expression as a predictor of OS for first-line chemotherapy plus cetuximab in the phase III FLEX study, using a novel method (H-score) to assign EGFR IHC status. We used this method to reassess samples from the SATURN study.Methods
The H-score method assigns an IHC score to each pt on a continuous scale of 0–300, based on the percentage of cells at different staining intensities (Pirker et al, Lancet Oncol 2012). As per this method, the outcome-based discriminatory threshold IHC H-score for our analysis was set at 200 and existing samples were re-read and classed as low (H-score <200) or high (≥200) EGFR protein expression. An exploratory cut-off was also assessed, at <10% or ≥10% membrane staining. PFS and OS (in terms of hazard ratios [HRs] and 95% confidence intervals [CIs] by Cox model, and log-rank p-values), were reanalysed based on these new classifications.Results
The original EGFR IHC analysis used samples from 370 and 372 pts in the erlotinib and placebo arms, respectively. This analysis examined existing samples from 351 and 361 pts in the erlotinib and placebo arms, respectively. PFS and OS according to EGFR IHC by different methods are shown in the Table.Conclusions
Re-scoring of EGFR IHC status in SATURN by H-score found similar benefit of erlotinib treatment in PFS or OS for subsets with high or low EGFR expression, in overall or EGFR WT populations.Table: 1271P
|SATURN protocol-defined EGFR IHC+||SATURN protocol-defined EGFR IHC–||EGFR IHC byH-score ≥ 200 (high)||EGFR IHC byH-score < 200 (low)||EGFR IHC byH-score ≥ 10%||EGFR IHC byH-score < 10%|
|n||erlotinib: 308 placebo: 313||erlotinib: 62 placebo: 59||erlotinib: 146 placebo: 157||erlotinib: 205 placebo: 204||erlotinib: 267 placebo: 287||erlotinib: 84 placebo: 74|
|PFS||0.69 (0.58–0.82) log-rank p < 0.0001||0.77 (0.51–1.14) log-rank p = 0.1768||0.68 (0.53–0.86) log-rank p = 0.0010||0.76 (0.62–0.93) log-rank p = 0.0076||0.71 (0.59–0.84) log-rank p < 0.0001||0.79 (0.57–1.10) log-rank p = 0.1627|
|OS||0.77 (0.64–0.93) log-rank p = 0.0063||0.91 (0.59–1.38) log-rank p = 0.6482||0.80 (0.62–1.05) log-rank p = 0.1099||0.80 (0.64–1.01) log-rank p = 0.0639||0.78 (0.64–0.96) log-rank p = 0.0161||0.85 (0.60–1.22) log-rank p = 0.3901|
|n (EGFR WT)||erlotinib: 170 placebo: 157||erlotinib: 28 placebo: 27||erlotinib: 86 placebo: 84||erlotinib: 103 placebo: 97||erlotinib: 147 placebo: 144||erlotinib: 42 placebo: 37|
|PFS in WT||0.79 (0.63–0.99) log-rank p = 0.0336||0.65 (0.37–1.13) log-rank p = 0.1146||0.69 (0.51–0.95) log-rank p = 0.0188||0.84 (0.63–1.12) log-rank p = 0.2166||0.78 (0.62–0.99) log-rank p = 0.0400||0.69 (0.44–1.10) log-rank p = 0.1126|
|OS in WT||0.77 (0.60–0.99) log-rank p = 0.0402||0.64 (0.35–1.20) log-rank p = 0.1608||0.78 (0.55–1.10) log-rank p = 0.1563||0.76 (0.55–1.05) log-rank p = 0.0964||0.78 (0.60–1.02) log-rank p = 0.0698||0.72 (0.43–1.19) log-rank p = 0.2004|
Note: HR < 1 is in favour of erlotinibDisclosure
W. Brugger: Financial Interest: Advisory Board.
F. Cappuzzo: Financial Interest: Advisory board, F. Hoffmann-La Roche Ltd.
I. Bara: Employed by F. Hoffmann-La Roche Ltd.
G. Klingelschmitt: Employed by F. Hoffmann-La Roche Ltd.
B. Klughammer: Stock Ownership: F. Hoffmann-La Roche Ltd Employed by F. Hoffmann-La Roche Ltd.
All other authors have declared no conflicts of interest.