Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial

Abstract

PurposeThe phase III ToGA trial established cisplatin, fluoropyrimidine and trastuzumab as the standard treatment in HER2-positive advanced gastric cancer (AGC). However, as demonstrated in HER2-negative AGC, oxaliplatin-based regimens could improve tolerance remaining effective. The aim of this trial was to explore the potential activity and safety of capecitabine, oxaliplatin (XELOX) and trastuzumab in patients with HER-2 positive advanced gastric cancer.MethodsWe conducted a multicentre, prospective, non-randomised, non-controlled, open-label and national (Spanish) phase II study. Patients with HER2-positive advanced gastric or gastro-oesophageal junction (EGJ) cancer received XELOX and trastuzumab as first-line treatment. Primary endpoint was objective tumour response rate (ORR).Results45 patients from ten hospitals in Spain were included from September 2011 to December 2013. Median age was 65 years, 82.2% were male, 69% had gastric cancer and 31% had EGJ tumours. At a median follow-up of 13.7 months (7.1–20.9), the estimated median progression-free survival and overall survival were 7.1 (95% CI 5.5–8.7) and 13.8 months (95% CI 10.1–17.4), respectively, with 8.9%, 37.8% and 31.1% of patients achieving complete response, partial response and stable disease. Regarding safety, 44.4% of the patients had grade 3 or greater adverse events, being the most frequent diarrhoea (26.6%), fatigue (15.5%), nausea (20%) and vomiting (13.3%). Only two patients (4.4%) developed asymptomatic grade 2 left ventricle ejection fraction reduction.ConclusionsXELOX-trastuzumab is a promising and effective therapy as first-line treatment for patients with HER2-positive AGC, with comparable results to the ones obtained with other “platinum-based” regimens. This scheme is feasible and tolerable with a low incidence of cardiac toxicity.

<p>Trastuzumab with FLOT Regimen for the Perioperative Treatment of Resectable HER2 + Advanced Gastric Cancer: A Retrospective Study</p>

“…A Spanish study showed that the ORR and DCR for trastuzumab combined with the XELOX regimen in the treatment of advanced gastric cancer patients were 46.7% and 77.8%, respectively. 13 The curative effect was worse than that of our study. In addition, we found that the cN+/ypN0 of the experimental group was 53.8%, while the cN+/ypN0 of the control group was only 35.7%.…”

“…5 A stage III ToGA clinical study showed that the efficacy of trastuzumab combined with an XP/FP regimen in patients with HER-2-positive advanced esophagogastric junction or gastric cancer was significantly better than that of patients receiving only chemotherapy. Median OS was 13.8 months (95% confidence interval [CI] [12][13][14][15][16] for patients assigned to the trastuzumab plus chemotherapy arm compared with 11.1 months (95% CI [10][11][12][13] in the chemotherapy group (hazard ratio [HR] 0.74; 95% CI 0.60--0.91; p = 0.0046). Especially in the patients with HER-2 immunohistochemistry 2 + and FISH positive or the patients with HER-2 immunohistochemistry 3 +, the survival improvement was more obvious, with the median OS better in the experimental arm (16.8 vs 11.8 months, HR: 0.65).…”

Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

“…Similar efficacy was also apparent in AGC patients without measurable lesions (HERBIS-1B study) [7]. Three phase II studies that assessed the combination of trastuzumab with capecitabine plus oxaliplatin reported a median OS, a median PFS, and an ORR of 13.8 to 21.0 months, 7.1 to 9.8 months, and 46.7% to 67.3%, respectively [8][9][10]. Trastuzumab in combination with S-1 plus oxaliplatin was also shown to provide a similar treatment outcome in a phase II study, with a median OS, a median PFS, and an ORR of 18.1 months, 8.8 months, and 70.7%, respectively [11].…”

<p>Contrast-Enhanced CT Parameters of Gastric Adenocarcinoma: Can Radiomic Features Be Surrogate Biomarkers for HER2 Over-Expression Status?</p>

“…[22][23][24] Recently, the development of targeted therapy, such as trastuzumab, has drawn attention to HER2 expression status. 25,26 Clinical studies have shown that several clinicopathological characteristics, such as, older age, male, intestinal type, and well-differentiation, were correlated with HER2 over-expression. 13,27 In this study, we found that the differentiation degree of GACs was also related with HER2 over-expression.…”