Perioperative trastuzumab, capecitabine and oxaliplatin in patients with HER2-positive resectable gastric or gastro-oesophageal junction adenocarcinoma: NEOHX phase II trial.

INTRODUCTION: Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal junction adenocarcinoma (GEJA). The addition of trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and we aimed to explore its role in the perioperative setting. MATERIAL AND METHODS: This Spanish, multicentre, open-label phase II trial evaluated the efficacy and toxicity of perioperative capecitabine, oxaliplatin and trastuzumab (XELOX-T) in patients with HER2-positive resectable GA or GEJA. The primary end-point was 18-months DFS; and secondary end-points included pathological complete response (pCR) rate, R0 resection rate, OS and toxicity (NCT01130337). RESULTS: Thirty-six patients were included. After three cycles of preoperative treatment, 14 patients (38% of the intention-to-treat population) had partial response and 18 (50%) had stable disease. Surgery was performed in 31 patients: 28 (90%) had R0 resection, three (9.6%) had a pCR and three (9.6%) died due to surgical complications. A total of 24 patients received post-operative XELOX-T, 22 of whom completed trastuzumab maintenance. Main grade III/IV toxicities included diarrhoea (33%), nausea and vomiting (8%). After a median follow-up of 24.1 months, 18-month DFS was 71% (95% confidence interval [CI], 53-83%); and an update after 102 months of follow-up showed a median OS of 79.9 months and a 60-month OS of 58% (95% CI, 40-73%). CONCLUSIONS: These data suggest that perioperative XELOX-T in patients with HER2-positive GA and GEJA is feasible and active. Further investigation in randomised studies is warranted.

Reduced folate carrier (RFC) as a predictive marker for response to pemetrexed in advanced non-small cell lung cancer (NSCLC).

INTRODUCTION: RFC is the major transport system in mammalian cells for folate cofactors and antifolate therapeutics. The aim of this study was to assess the predictive value of RFC expression in patients receiving pemetrexed for advanced NSCLC. METHODS: The study was carried out in a population of 48 patients with advanced NSCLC which have received pemetrexed monotherapy in second and third line. RFC expression was assessed using a two-step model of immunohistochemical staining in paraffin-embedded tissue samples. RESULTS: RFC expression was detected in 16 (33 %) patients. In the global population, the median progression free survival (PFS) and the median overall survival (OS) were 3.3 and 6.5 months respectively. The subgroup of patients with expression of RFC had a tendency to better median PFS (4.5 vs 2.8 months; p = 0.926) and median OS (11.7 vs 4.8; p = 0.150). In patients with adenocarcinoma histology and RFC expression median OS after treatment with pemetrexed was 14.4 months versus 5.0 in those with adenocarcinoma but without RFC expression (p = 0.039). CONCLUSIONS: These results suggest the possible relation between RFC expression and response to treatment with antifolates (pemetrexed) independently of the tumor histology. Further studies are required to confirm these results.