Phase II study of trastuzumab with modified docetaxel, cisplatin, and 5 fluorouracil in metastatic HER2-positive gastric cancer

Abstract

Background: Trastuzumab with cisplatin and fluoropyrimidine is the standard treatment in metastatic HER2-positive gastric or gastroesophageal (GE) junction adenocarcinoma; however, there is limited data on the efficacy of trastuzumab in combination with a three-drug regimen in this setting. We examined the efficacy and safety of modified docetaxel, cisplatin and 5 fluorouracil (mDCF) plus trastuzumab in a single-arm multicenter phase II trial.

Methods: Previously untreated patients with HER2-positive metastatic gastric or GE junction adenocarcinoma were treated with mDCF and trastuzumab every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included objective response rate, overall survival (OS), and toxicity.

Results: We enrolled 26 patients with metastatic HER2-positive gastric or GE junction adenocarcinoma between February 2011 and June 2015. The median age of patients was 62 years; 96% had a Karnofsky performance status equal to or greater than 80%. With a median follow-up of 25.4 months, the 6-month PFS was 73% (95% CI 51-86%). The objective response rate was 65%, the median PFS was 13 months (95% CI 6.4-20.7) and the median OS was 24.9 months (95% CI 14.4-42.5). Grade 3/4 toxicities included neutropenia (42%), fatigue (23%), and hypophosphatemia (15%). There were no episodes of febrile neutropenia.

Conclusion: The combination of mDCF and trastuzumab is effective and safe in patients with metastatic HER2-positive gastric or GE junction adenocarcinoma and can be considered as an option for selected patients. This trial is registered at ClinicalTrials.gov, number NCT00515411.

Keywords: Docetaxel; Gastric cancer; HER2; Trastuzumab.

Conflict of interest statement

Conflicts of Interest: Y.Y. Janjigian has received research funding from Boehringer Ingelheim, Bayer, Genentech/Roche, Bristol-Myers Squibb, Eli Lilly, and Merck and serves on advisory boards for Merck Serono, Bristol-Myers Squibb, Eli Lilly, Pfizer, and Merck.

Figures

Figure 1.

Treatment response of each patient, quantified as best percentage change in sum of longest tumor diameters of target lesions. * One patient with a non-target 14-mm lymph node (short axis) was included in this analysis.

Figure 2.

Outcomes in patients treated with first-line mDCF and trastuzumab. (a) Progression-free survival (PFS) and (b) overall survival (OS).

Figure 3.

Genomic analysis of advanced HER2-positive gastric cancer. Oncoprint depicts alterations in selected genes of interest in 11 HER2-positive gastric cancer patients treated with mDCF and trastuzumab. Correlation with progression-free survival (a) and overall survival (b) are described.