1226O - Biomarker analyses and overall survival (OS) from the randomized, placebo-controlled, phase 3, fastact-2 study of intercalated erlotinib with first-...
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||NSCLC, metastatic I|
Non-Small-Cell Lung Cancer, Metastatic
T.S.K. Mok1, J.S. Lee2, L. Zhang3, C. Yu4, S. Thongprasert5, G.E.I. Ladrera6, V. Srimuninnimit7, M. Truman8, B. Klughammer9, Y. Wu10
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 < 0.0001 (Mok et al. ASCO 2012). We report OS results and correlations of biomarkers with PFS for this study.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||<0.0001|
|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||<0.0001|
|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|
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.