The Impact of Pembrolizumab as a Salvage Therapy Based on HER2 Expression in Advanced Gastric Cancer

TL;DR

Pembrolizumab, an immune therapy, is more effective in treating advanced gastric cancer in patients who are HER2-positive compared to those who are HER2-negative.

Contribution

This study demonstrates that pembrolizumab as salvage therapy shows significantly better outcomes in HER2-positive advanced gastric cancer patients.

Findings

50% of HER2-positive patients had a partial response to pembrolizumab, compared to 4.9% of HER2-negative patients.

Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients.

Disease control rates were higher in HER2-positive patients (70%) compared to HER2-negative patients (37.8%).

Abstract

This study evaluated the effectiveness of salvage pembrolizumab in advanced gastric cancer (AGC) patients based on HER2 expression. Conducted at Samsung Medical Center from November 2017 to March 2023, it involved 113 patients treated with pembrolizumab. Twelve patients (10.6%) were HER2-positive, and 101 were HER2-negative. Results showed no complete responses among 92 evaluable patients. However, 50% of HER2-positive patients had a partial response compared to 4.9% of HER2-negative patients (p < 0.001). Disease control rates were 70% for HER2-positive and 37.8% for HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). This indicates that salvage pembrolizumab monotherapy is more effective in HER2-positive AGC patients.

Immune checkpoint inhibitors (ICIs) are used as salvage treatments for advanced gastric cancer (AGC) regardless of HER2 status. This study assessed the efficacy of ICIs based on HER2 expression in AGC patients who received pembrolizumab as salvage monotherapy at Samsung Medical Center from November 2017 to March 2023. HER2 status was determined via immunohistochemistry, and tumor response and survival outcomes were compared accordingly. Among the 113 patients analyzed, with a median age of 61 years and 64.6% being male, 12 patients (10.6%) were HER2-positive, and 101 patients (89.4%) were HER2-negative. Of 92 evaluable patients, none had a complete response. However, 50% of HER2-positive patients had a partial response, compared to 4.9% of HER2-negative patients (p < 0.001). The disease control rate was 70% in HER2-positive and 37.8% in HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). Pembrolizumab as a salvage chemotherapy for the treatment of AGC demonstrated superior effectiveness in HER2-positive patients compared with HER2-negative patients.

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