NEOHX study: Perioperative treatment with trastuzumab in combination with capecitabine and oxaliplatin (XELOX-T) in patients with HER-2 resectable stomach or esophagogastric junction (EGJ) adenocarcinoma—18 m DFS analysis.

Abstract

107 Background: Perioperative chemotherapy has demonstrated better OS and DFS than surgery alone in resectable stomach or EGJ adenocarcinoma. Trastuzumab has improved OS when added to chemotherapy in pts with HER-2 + metastatic gastric cancer and is interesting to explore its role in the perioperative setting. Methods: A Spanish, multicenter, open-label phase II study evaluated the efficacy and toxicity profile of perioperative XELOX-T (Capecitabine 1000 mg/m2/12h po days 1-14, oxaliplatin 130 mg/m2 day 1, trastuzumab 8 mg/kgà6 mg/kg day 1, q3w ; 3 preoperative cycles and 3 postsurgery cycles followed by 12 cycles of trastuzumab monotherapy) in patients with T1-2N+M0 or T3-4NxM0 resectable stomach or EGJ adenocarcinoma, HER-2+ ( IHQ3+ or IHQ2+/FISH+). The primary endpoint was 18 months DFS, secondary endpoint included pCR, R0 resection rate, ORR, toxicity of preoperative treatment (NCI CTC v3.0 criteria) and biomarker analysis. Results: From June 2010 to March 2012, 36 pts were included: median age 65 (39-85); ECOG 0/1/2: 16/19/1 pts; localization: stomach 21 pts, EGJ 15 pts; histologic type: intestinal: 23 pts, diffuse: 4 pts, mixed: 1pt, not specified 8 pts; TNM: T 4: 7 pts; N+: 31 pts. Preoperative XELOX-T: Response: PR: 14 pts (39%), SD: 18 pts, PD: 0 pts, NE: 4 pts. Surgery was performed in 31 pts: R0: 28 pts (78%, 95% CI: 61-90%), R1: 1 pt, R2: 2 pts (1 had peritoneal carcinomatosis); pCR was observed in 3 pts (8.3 %; 95% CI: 2-22%). Two pts died due to surgical complications. After R0/R1 resection, postoperative XELOX-T was administered to 24 patients, 22 of whom underwent T monotherapy. G3-4 toxicity (>5% of pts): diarrhea 33%, nauseas and vomiting 8% and pneumonia, anemia, neutropenia, anorexia, asthenia and pleural effusion with pneumothorax: 5.5%. With a median follow up of 24.1 months, 18m DFS is 71% (95% CI: 53-83%), 24 m DFS is 60% and median DFS and OS has not been reached. Conclusions: These data suggest that perioperative XELOX+T in HER-2 positive resectable stomach or esophagogastric junction adenocarcinoma is feasible and has promising activity. Clinical trial information: NCT01130337.

Clinical impact of tumour biology in the management of gastroesophageal cancer

“…Two phase II studies, one from Spain 88 and one from Germany 89 , reported the feasibility of neoadjuvant platinum–5-FU-based chemotherapy with trastuzumab, and reported interesting response rates: 36 patients were included in the Spanish study, and showed preoperative capecitabine/oxaliplatin-trastuzumab was feasible. An R0 resection was achieved in 28 patients (78%) and a histopathological complete response was observed in three patients (8.3%).…”

“…An R0 resection was achieved in 28 patients (78%) and a histopathological complete response was observed in three patients (8.3%). 88 The German study 89 reported histopathological complete responses in 10 out of 45 patients (22.2%) with HER2-positive locally advanced gastric cancer who received the combination of trastuzumab and standard chemotherapy. This finding raises hope that high response rates can be achieved with trastuzumab plus chemotherapy combinations in the neoadjuvant setting and might translate into improved survival rates.…”

Impact of HER2 status in resected gastric or gastroesophageal junction adenocarcinoma in a Western population

“…We currently have the results of two small, phase II studies of perioperative chemotherapy, the NEOHX and HER-FLOT studies, in which trastuzumab was added to a CAPOX or FLOT regimen, respectively. Rates of pathological complete response were 8.3% and 22.2%, respectively, without significant increases in toxicity or surgical complications [21,22].…”

Pathologic Complete Response After Preoperative Chemotherapy With a Regimen Containing Trastuzumab in Esophagogastric Junction Adenocarcinoma: A Case Report

“…In the present case, because the high level of CEA and tumor invasion to the diaphragm indicated difficulty in R0 resection, surgery was planned after preoperative chemotherapy. In the NEOHX study, perioperative treatment using trastuzumab in combination with capecitabine and oxaliplatin led to a 19% pathological complete response rate 18 . Therefore, we used a regimen consisting of trastuzumab in combination with capecitabine and cisplatin as preoperative chemotherapy for this EGJA patient with HER2 positivity.…”