A Single Arm Clinical Trial to Assess the Efficacy and Safety of Panitumumab (Vectibix) in combination with FOLFOX4 Chemotherapy as 1st line treatment in Subjects with Metastatic Gastric or Gastroesophageal Junction adenocarcinoma (VEGA trial). A multicenter Phase II SICOG trial 0802

Background: EGFR overexpression occurs in 27-55% of gastroesophageal adenocarcinomas, and correlates with poor prognosis. We aimed to assess the efficacy and safety of the anti-EGFR antibody Panitumumab (PANIT) in addition to Oxaliplatin, 5-FU and Leucovorin (FOLFOX 4) as front-line treatment in patients (pts) with metastatic gastric or gastroesophageal -junction (GEJ) adenocarcinoma. Primary endpoint was response rate (ORR); secondary endpoints were duration of and time to response (DoR and TTR), safety, PFS and OS. Patients and methods: Between October 2009 and July 2013 we enrolled 65 pts with untreated metastatic gastric(80%) and GEJ (20%) adenocarcinoma at 8 referral SICOG centers. Eligible pts were 69% males, median age 62 years (y) (33-82), 60% and 40% ECOG PS 1 and 0, respectively; 72% and 28% presented with synchronous and metachronous metastases, respectively; 69% had nodal plus visceral metastases. Pts received FOLFOX 4 for a maximum of 12 cycles plus PANIT (6 mg/Kg) for a minimum of 4 cycles or until progression or unacceptable toxicity, q1-14. Response was evaluated every 4 cycles according to modified-RECIST criteria, in intention to treat population . Gene expression profiling studies are ongoing. Results: Eleven and 54 (83%) pts received < and = or > than 4 cycles, respectively. Median number of administered FOLFOX cycles was 8 (1-12) and 43% of pts received all 12 planned cycles; median number of administered PANIT cycles was 8 (1-28) and 43% received 12 or more PANIT cycles. ORR was 42%, median TTR was 2 months (m) (1-11); median DoR 8 m(2-19); median PFS 5.6 m (0.6-16.2); median OS 11 m (0.6-46.3); 1 y PFS and 1y OS rates were 11.4% and 42.7%, respectively. Most frequent PANIT-related AEs were skin toxicity, asthenia, diarrhea and mucositis; 3 pts discontinued PANIT, 1 for infusional reaction, 1 for rash G3, 1 for mucositis G3. No PANIT-related deaths occurred. Conclusions: Addition of PANIT to FOLFOX 4 in gastric and GEJ cancer patients seems to be effective and safe, however ongoing tissue gene expression profiling analyses would identify subpopulation of pts benefiting more from anti-EGFR target therapy in this setting.