Pembrolizumab Boosts Response Rates in HER2+ Gastroesophageal Cancer
Seoul, Wednesday, 19 February 2025.
A phase II trial finds adding pembrolizumab to chemotherapy enhances responses, achieving a 69% rate in advanced HER2+ gastroesophageal cancer, highlighting its potential in combination treatments.
Trial Results Show Promising Efficacy
The recently published phase II trial demonstrates significant benefits of incorporating pembrolizumab into first-line treatment regimens. The study, published on February 17, 2025, revealed an impressive objective response rate of 69% and a median progression-free survival of 11.9 months in patients with advanced HER2-positive gastroesophageal cancer [1]. This combination approach, which sequentially added pembrolizumab to traditional 5FU/platinum chemotherapy plus trastuzumab, shows particular promise for patients with dual HER2-positive and PD-L1 positive status [1].
Understanding the Mechanism
The trial’s comprehensive biomarker analysis revealed fascinating insights into how the treatment works. Researchers observed that trastuzumab initially triggers natural killer cell infiltration in HER2-positive tumor beds, while increasing Fc receptor expression in macrophages [1]. This remodeling of the tumor environment is further enhanced when pembrolizumab is introduced, particularly in PD-L1 positive samples [1]. However, patients should be monitored carefully as pembrolizumab can cause severe immune-related adverse reactions affecting various organ systems [2].
Implications for Future Treatment
These findings represent a significant step forward in the treatment of HER2-positive gastroesophageal cancer. The study’s results suggest that carefully sequenced combination therapy could become a new standard approach for specific patient subgroups [1]. The trial’s insights into tumor heterogeneity and immune cell features provide valuable guidance for patient selection, potentially helping clinicians identify those most likely to benefit from this treatment approach [1]. However, the presence of TGF-β signaling in HER2-negative tumor regions was associated with non-response, indicating the need for additional strategies in certain cases [1].