Prognostic factors and treatment response in HER2-positive gastric cancer patients receiving trastuzumab deruxtecan: secondary analysis of the EN-DEAVOR study

Abstract

Background

EN-DEAVOR was a multi-institutional retrospective study evaluating the effectiveness and safety of trastuzumab deruxtecan (T-DXd) in gastric cancer patients. This secondary analysis investigated prognostic factors for real-world progression-free survival (rwPFS) and objective response rate (ORR) for T-DXd as third- or later-line treatment.

Patients and methods

Patients aged ≥20 years with histopathologically confirmed human epidermal growth factor receptor 2 (HER2)-positive unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma, who had worsened after chemotherapy, were included. Patients received T-DXd as third- or later-line therapy between September 2020 and September 2021. Univariate and multivariate analyses identified prognostic factors for rwPFS and ORR.

Results

Of the 307 patients, 75.6% were male and 69.1% were aged ≥65 years. The median duration of prior trastuzumab treatment was 6.5 months (range 0-81.5 months). Multivariate analysis showed HER2 immunohistochemistry (IHC) 3+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86], intestinal type lesions (HR 0.59, 95% CI 0.43-0.79), modified Glasgow Prognostic Score (mGPS) 0 and 1 (HR 0.71, 95% CI 0.53-0.95), and longer duration of prior trastuzumab treatment (≥ median) (HR 0.75, 95% CI 0.58-0.97) as positive prognostic factors for rwPFS. Longer prior trastuzumab treatment was also a positive prognostic factor for ORR (odds ratio 2.02, 95% CI 1.13-3.63).

Conclusions

Patients with clinical benefits from prolonged trastuzumab treatment are likely to benefit from T-DXd. Similarly, HER2 IHC 3+, intestinal type lesions, and better mGPS (0 or 1) are associated with longer rwPFS. However, T-DXd should not be withheld even in patients without these factors, as a median PFS of 3.42 months was observed in those with the shortest prior trastuzumab exposure.