205P - Efficacy analysis of gefitinib +/- ficlatuzumab in serum proteomic based subgroups of patients with previously untreated lung adenocarcinoma

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Thoracic Malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological Therapy
Presenter Tony Mok
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors T.S.K. Mok1, E. Tan2, S.L. Greater3, G. Chang4, J. Yang5, J. Gyuris6, M. Han7, P. Komarnitsky6, F. Payumo8, G. Pestano9, J. Roder9, D. Spinella9, Z. Weng6, K. Park10
  • 1Department Of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, CN- - Shatin, Hong Kong/CN
  • 2Department Of Medical Oncology, National Cancer Centre Singapore, Singapore/SG
  • 3Internal Medicine, Prince of Songkla University, Songkhla/TH
  • 4N/a, Veterans General Hospital, Taichung/TW
  • 5Department Of Oncology, National Taiwan University Hospital, Taipei City/TW
  • 6Clinical Research, AVEO Oncology, 02142 - Cambridge/US
  • 7Oncology, AVEO Pharmaceuticals, Inc., Cambridge/US
  • 8N/a, AVEO Oncology, 02142 - Cambridge/US
  • 9N/a, Biodesix, Boulder/US
  • 10Department Of Internal Medicine, Hematology, Oncology, Samsung Medical Center Sungkyunkwan University SOM, KR-135-710 - Seoul/KR

Abstract

Aim

Ficlatuzumab (F), a humanized anti-hepatocyte growth factor (HGF) IgG1 mAb, inhibits c-MET receptor activation by neutralizing HGF. HGF/c-MET pathway activation has been implicated in epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer. A randomized Phase 2 study of gefitinib (G) +/- F in Asian patients with previously untreated lung adenocarcinoma (±EGFR mutations) failed to demonstrate improved overall survival (OS) or progression-free survival (PFS) over G alone (NCT01039948) in the intent-to-treat population. VeriStrat® (VS) is a multivariate serum proteomic test that utilizes mass spectrometry to assign a “GOOD” (VSG) or “POOR” (VSP) classification and has demonstrated broad prognostic and predictive utility for EGFR TKI treatments. In part, VS appears to measure a host inflammatory state that may stimulate tumors via alternative pathways, including HGF secretion.

Methods

183 blinded unique patient pretreatment serum samples from the study were sent for VS analysis. Clinical outcomes of F + G vs G alone were analyzed in VS subgroups.

Results

183 serum samples were assigned a VS label (VSG = 145, VSP = 35, and 3 “Indeterminate”). Addition of F to G provided significant clinical benefit to the VSP subgroup: OS hazard ratio (HR) 0.41, P = .032; medians = 23.9 mo for F + G (N = 18) vs 5.8 mo for G alone (N = 17) and PFS HR 0.41, P = .014; medians = 7.4 mo for F + G vs 2.3 mo for G alone. No benefit was observed in the VSG subgroup in either OS (HR 1.18, P = .492; median 24.7 mo for F + G [N = 69] vs not reached for G alone [N = 76]) or PFS (HR 1.06, P = .753; median 5.6 mo for F + G vs 5.6 mo for G alone). Unadjusted interaction test for treatment and VS was statistically significant for OS (HR = 3.31, P = .013) and PFS (HR = 2.51, P = .019). Despite the small sample sizes, similar patterns in OS and PFS based on VS stratification were also observed in patients with known EGFR mutations (n = 71).

Conclusions

VS may be predictive for clinical benefit of F + G over G (OS and PFS) in patients classified as VSP. A prospective confirmatory study using VS as predictive biomarker on the combination of F + EGFR-TKI in EGFR mutation–positive patients is planned.

Disclosure

J.C. Yang: Advisory boards: Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Roche/Genetech, Astrazeneca, Merck, Bayer, Clovis Oncology Corporate sponsored research: Boehringer Ingelheim; J. Gyuris, M.Han, F. Payumo and Z. Weng have declared: AVEO Oncology employee • Stock • Salary; P. Komarnitsky: (former) AVEO Oncology employee; G. Pestano, J. Roder and D. Spinella have declared: Biodesix employee • Stock • Salary; K. Park: Advisory boards: AVEO, Astellas, AZ, BI, Clovis, Daiichi Sankyo, Eli Lilly, Kyowa Hakko Kirin, Novartis, Roche. All other authors have declared no conflicts of interest.