Background: EGFR and HGF/c-Met pathways are often deregulated in AGEA. We assessed whether EGFR or HGF inhibition with panitumumab or rilotumumab is beneficial in the first-line treatment of pts with AGEA. Methods: Pts ≥18 yrs with non-HER2+, measurable AGEA and ECOG performance status (PS) 0-1 were randomized (minimization procedure; stratification factors: Lauren classification, disease stage, center) to mFOLFOX6 (oxaliplatin 85 mg/m², folinic acid 400 mg/m², fluorouracil: 400 mg/m² bolus then 2400 mg/m² over 46 h) alone (arm A) or combined to panitumumab (6 mg/kg; arm B) or rilotumumab (10 mg/kg; arm C), every 2 weeks until limiting toxicity or disease progression. The primary endpoint was 4-month progression-free survival rate (4-PFS) (Fleming’s one-step design, one-sided Α=5%, Β=10%, H0: 40%; H1: 60%; 153 evaluable pts needed). Results: 162 pts (median age, 64 [range, 23-87]; ECOG PS 0/1, 33/67%) were enrolled from 2011/01/14 to 2013/08/19 in 29 French centers. Most had metastatic (97%), intestinal (69%) adenocarcinoma of the stomach (50%) or GE junction (30%). Main results were (median follow-up, 23.6 months; 95%CI, 19.7-27.3): Conclusions: All combination regimens reached the primary study endpoint. Adding panitumumab or rilotumumab seemed more toxic and not more effective than mFOLFOX6 alone. Subgroup analyses according to tumor biomarker status (e.g., RAS/BRAF and MET) will be presented later. Clinical trial information: 2009-012797-12.

¹n = 159 pts evaluable for safety. ² G5, 1/4/3 pts, respectively. ³n = 158 evaluable pts (intent-to-treat population).