Additions of trastuzumab to preoperative chemotherapy or chemoimmunotherapy for patients with potentially resectable stage III to IVB HER2-positive gastric cancer

Abstract

Background: Whether the addition of trastuzumab to chemo(immuno)therapy for the preoperative treatment of patients with potentially resectable HER2-positive gastric cancer has clinical benefits remains to be explored. This real-world observational study was designed to evaluate the efficacy and safety of trastuzumab plus chemo(immuno)therapy for neoadjuvant or conversion therapy in patients with potentially resectable HER2-positive gastric cancer.

Methods: We retrospectively collected the clinical data of treatment-naïve patients with potentially resectable stage III to IV_B HER2-positive gastric cancer who received preoperative therapy prior to D2 gastrectomy. The main outcomes of interest included tumour regression grade (TRG), treatment-related adverse events (TRAEs), and event-free survival (EFS).

Results: A total of 40 patients were included in the analysis, specifically, 27 patients (67.5%, 95% CI 0.520-0.799) received preoperative trastuzumab plus chemo(immuno)therapy, and 13 patients (32.5%, 95% CI 0.201-0.480) received chemo(immuno)therapy. All these patients subsequently underwent D2 gastrectomy. Regarding surgical outcomes, TRG0/1 rates were 33.3% (95% CI 0.186-0.522) in the trastuzumab-containing treatment group and 15.4% (95% CI 0.043-0.422) in the chemotherapy/chemoimmunotherapy group. Regarding safety, 66.7% (95% CI 0.478-0.814) of patients in the trastuzumab-containing treatment group and 61.5% (95% CI 0.355-0.823) of patients in the chemotherapy/chemoimmunotherapy group experienced preoperative TRAEs. The probabilities of EFS were not statistically significant between the two groups by the last follow-up.

Conclusion: Additions of trastuzumab to preoperative chemotherapy or chemoimmunotherapy resulted in a TRG0/1 rate of 33.3% among patients with potentially resectable HER2-positive gastric cancer, and the combined regimen exhibited a favourable safety profile.

Keywords: HER2-positive gastric cancer; immune checkpoint blockade; preoperative therapy; trastuzumab; tumour regression grade.

Figure 1

Assessments of best tumour responses to preoperative treatment based on RECIST and surgical outcomes of the patients.

Figure 2

Tumour response in a patient who received preoperative treatment with trastuzumab, pembrolizumab, and XELOX chemotherapy, and subsequently achieved a pathological TRG0. (A) H&E staining images (a) at baseline and (b–e) post-operative. (B) Radiographical images at baseline and after preoperative treatment. (C) Gastroscopy images at 32 months post-surgery, with no evidence of recurrence observed.

Figure 3

Treatment process and Kaplan–Meier curves for event-free survival (EFS). (A) Swimmer plot of the treatment process and follow-up of the patients from the time of diagnosis. (B–D) Kaplan–Meier curves for EFS (B) in patients receiving trastuzumab-containing treatment versus patients receiving chemo(immuno)therapy (P=0.487), (C) in patients receiving trastuzumab plus chemotherapy versus patients receiving chemotherapy alone (P=0.364), and (D) in patients receiving trastuzumab, PD-1 blockade and chemotherapy versus patients receiving PD-1 blockade plus chemotherapy (P=0.988).