J Clin Oncol: Efficacy and safety of Trastuzumab Deruxtecan in the treatment of HER2 low-expression gas/gastroesophageal junction cancer

Human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor that regulates cell cycle progression, cell proliferation, differentiation and survival, and angiogenesis signaling pathways
.
About one in five gastric/gastroesophageal junction (GEJ) cancers have HER2 overexpression or amplification
.
HER2 expression levels are heterogeneous within and between tumors and vary with anti-HER2 therapy
.

This study aims to evaluate the efficacy and safety
of trastuzumab Deruxtecan (T-DXd) in the treatment of HER2-low expression of gastric or gastroesophageal junction adenocarcinoma.

Patients with locally advanced or metastatic gastric/GEJ adenocarcinoma with low expression of HER2-who had received at least two prior regimens (including fluorouracil and platinum) but had not received anti-HER2 therapy were recruited (cohort 1: immunohistochemical 2+/in situ hybridization negative; Cohort 2: Immunohistochemistry 1+), T-DXd 6.
4 mg/kg 1 time/3 weeks
.
The primary endpoint was objective response rate
.

Overall survival and progression-free survival of test patients

Nineteen of the 21 patients enrolled in cohort 1 and 21 of the 24 patients enrolled in cohort 2 with a definitive HER2 test received T-DXd with measurable tumors
at baseline.
Five patients in cohort 1 achieved a definite partial response, with an objective response rate of 26.
3%; Two patients in Cohort 2 achieved a partial response with an objective response rate of 9.
5%.

Thirteen (68.
4%) patients in Cohort 1 and 12 (60.
0%) patients in Cohort 2 experienced tumor volume reduction
.
The median overall survival of cohorts 1 and 2 was 7.
8 and 8.
5 months, respectively, and the median progression-free survival was 4.
4 months and 2.
8 months
, respectively.

Adverse reactions

The most common grade 3 and older adverse effects requiring urgent treatment were anaemia (cohort 1 vs cohort 2: 30.
0% versus 29.
2%), decreased neutrophil count (25.
0% versus 29.
2%), and decreased appetite (20.
0% versus 20.
8%)
.
One patient in each cohort developed drug-associated interstitial pulmonary/pneumonia (grade 1 or 2).

There were no drug-related deaths
.

The study provides preliminary evidence that T-DXd is clinically active
in a large number of pretreated patients with low HER2-expressing gas/gastroesophageal junction adenocarcinoma.

Original source:

Kensei Yamaguchi, et al.
Trastuzumab Deruxtecan in Anti–Human Epidermal Growth Factor Receptor 2 Treatment–Naive Patients With Human Epidermal Growth Factor Receptor 2–Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial.
Journal of Clinical Oncology.
November, 2022.
https://ascopubs.
org/doi/full/10.
1200/JCO.
22.
00575