1226O - Biomarker Analyses and Overall Survival (OS) from the Randomized, Placebo-Controlled, Phase 3, Fastact-2 Study of Intercalated Erlotinib with First-Line Chemotherapy in Advanced Non-Small-Cell Lung Cancer (NSCLC)

Abstract

ABSTRACT Background FASTACT-2 is a randomized, placebo-controlled, phase 3 study in first-line advanced NSCLC, which met its primary endpoint of significantly prolonged PFS with intercalated erlotinib and chemotherapy: median 7.6 vs 6.0 months; HR = 0.57; p Methods Patients (pts) with untreated stage IIIB/IV NSCLC and ECOG PS 0/1 received up to 6 cycles of gemcitabine (1,250 mg/m2 on d1 & 8) plus platinum (carboplatin AUC = 5 or cisplatin 75 mg/m2 on d1) q4w, with either intercalated erlotinib (150 mg/day on d15–28; GC-E; n = 226) or placebo (GC-P; n = 225). Pts without progression received maintenance erlotinib or placebo until progression, unacceptable toxicity or death. Provision of tumour samples was encouraged; tests were conducted at a central laboratory and prioritized as follows: EGFR mutation; KRAS mutation (both by PCR-based test [COBAS]); ERCC1 expression by immunohistochemistry (IHC; median cut-off); EGFR gene copy number by fluorescence in-situ hybridization (FISH); and EGFR IHC. Results OS data are not fully mature yet (45.1% and 52.4% of pts in GC-E and GC-P arms with event, respectively, in Oct 2011), but a trend towards prolonged OS with GC-E vs GC-P was observed: HR = 0.78 (95% CI 0.60–1.02); p = 0.0686; median 18.3 vs 14.9 months. Updated OS data with June 2012 cut-off will be presented. A total of 283/451 pts (62.7%) provided samples for biomarker analyses. The table shows correlations with PFS for the overall biomarker populations and the EGFR wild-type (WT) subgroup. Conclusions As expected, the EGFR mutation-positive (Mut+) subgroup had the strongest PFS benefit with intercalated erlotinib and first-line chemotherapy. ERCC1 IHC+ status was also associated with longer PFS with GC-E vs GC-P, even in pts with known EGFR WT status. Biomarker subgroup HR for PFS (95% CI) Median PFS with GC-E vs GC-P, months p-value EGFR Mut+ (n = 97) 0.21 (0.12–0.35) 15.6 vs 6.9 EGFR WT (n = 136) 0.95 (0.67–1.34) 7.1 vs 5.9 0.7511 KRAS Mut+ (n = 21) 0.63 (0.25–1.58) 6.0 vs 4.5 0.3169 KRAS WT (n = 202) 0.51 (0.37–0.70) 8.0 vs 6.8 EGFR WT and KRAS Mut+ (n = 21) 0.63 (0.25–1.58) 6.0 vs 4.5 0.3169 EGFR WT and KRAS WT (n = 109) 1.01 (0.68–1.49) 6.6 vs 6.5 0.9609 ERCC1 IHC+ (n = 70) 0.51 (0.30–0.85) 9.0 vs 5.4 0.0091 ERCC1 IHC– (n = 71) 0.65 (0.39–1.08) 7.6 vs 7.2 0.0931 EGFR WT and ERCC1 IHC + (n = 37) 0.55 (0.27–1.12) 7.6 vs 4.6 0.0941 EGFR WT and ERCC1 IHC –(n = 38) 1.10 (0.56–2.18) 7.3 vs 7.2 0.7751 EGFR FISH+ (n = 34) 0.26 (0.11–0.64) 12.9 vs 5.9 0.0017 EGFR FISH– (n = 48) 0.67 (0.37–1.22) 7.5 vs 6.0 0.1880 EGFR WT and EGFR FISH+ (n = 11) 0.69 (0.18–2.68) 7.8 vs 7.6 0.5865 EGFR WT and EGFR FISH– (n = 31) 0.90 (0.42–1.92) 7.0 vs 5.7 0.7795 EGFR IHC+ (n = 76) 0.51 (0.31–0.86) 8.1 vs 6.0 0.0091 EGFR IHC– (n = 37) 0.40 (0.18–0.88) 10.2 vs 6.7 0.0179 EGFR WT and EGFR IHC+ (n = 38) 0.83 (0.42–1.63) 7.4 vs 5.8 0.5842 EGFR WT and EGFR IHC– (n = 22) 0.48 (0.18–1.29) 7.8 vs 7.2 0.1305 Disclosure T.S.K. Mok: Ad Boards: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, BeiGene, AVEO, Pfizer, Taiho, Boehringer Ingelheim, GlaxoSmithKline Biologicals Board of Directors: IASLC Research sponsorship: AstraZeneca Employed by Chinese University of Hong Kong. L. Zhang: Ad Boards: AstraZeneca, Lilly, BI, Aventis Research sponsorship: AstraZeneca, Aventis, Hengrui Pharm. C. Yu: Ad Boards: Roche, AstraZeneca, Pfizer, Takeda. M.I. Truman: Stock ownership: Roche Employed on a 12 month contract by Roche Products Ltd. B. Klughammer: Stock ownership: F. Hoffmann-La Roche Employed by: F. Hoffmann-La Roche. Y. Wu: Research funding: Roche, Pfizer, AstraZeneca Speaker fees from: Roche, Pfizer, AstraZeneca, Eli Lilly, Sanofi Aventis. All other authors have declared no conflicts of interest.