HER2-Low Gastric Cancer May Be a Distinct Disease Subtype

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Patients with HER2-low gastric cancer tended to have distinct characteristics compared to those with HER2-negative or -positive disease, warranting more research into this group, research found.

The features of patients with HER2-low advanced gastric cancer were distinct from those with HER2-positive or negative disease, though survival outcomes among the three groups were comparable, according to recent research that was presented at the 2022 Gastrointestinal Cancers Symposium, a conference put on by the American Society of Clinical Oncology.

HER2-low is a new classification of patients with cancer whose disease has some HER2 proteins on the cell surface, but not enough to be classified as HER2-positive. HER2-low breast cancer recently became a new subtype for patients with the disease, and led to the FDA approval of Enhertu (fam-trastuzumab-deruxtecan-nxki).

Now, research is being conducted to determine if HER2-low could be a useful biomarker in gastric cancers as well.

The aim of the retrospective analysis was to determine if HER2-low in gastric cancer can be distinguishable from HER2-positive or HER2-negative disease.

For this study, 21% of patients had HER2-low inoperable or recurrent advanced gastric cancer, and had immediately identifiable clinicopathological features in sex, histology (how tumors look and behave) and metastatic site serum levels between those with HER2-negative and HER2-positive disease.

Between 2011 and 2018, 734 patients with advanced gastric cancer were treated with fluoropyrimidine and platinum-containing chemotherapy, of which 410 had HER2-negative disease, 154 were HER2-low, and 170 had HER2-positive disease.

Most patients were male across all three groups. The stomach was the most common location of the primary tumor with others including esophagogastric junction or the cardia, with most being metastatic upon diagnosis.

Most patients did not receive a gastrectomy prior to treatment, and it was common for patients to have two or more metastases.

The metastatic sites were split between either the liver (18.3% vs 24.8% vs 46.5%), distant lymph node (29.5% vs 37.0% vs 37.6%), or peritoneum (56.3% vs 44.8% vs 21.8%) in patients with HER2-negative, HER2-low, or HER2-positive disease, respectively.

The average overall survival — time from treatment until death of any cause —was 15.7 months in both the HER2-negative group and HER2-low disease group, and 21.7 months for those with HER2-positive advanced gastric cancer.

Progression-free survival, which is the time from treatment until the cancer spreads or worsens, was evaluated if patients received subsequent chemotherapies. In those receiving taxane therapy, the average progression-free survival was 3.3 months, 3.5 months and 4.1 months, in the HER2-negative, HER2-low and HER2-positive disease, respectively.

The progression-free survival for the three groups receiving irinotecan was 2.6 months, 2.4 months and 2.5 months. For those receiving Opdivo (nivolumab), the progression-free survival was 1.9 months, 2.1 months and 2.7 months. Across all three regimens, there was no statistical difference in progression-free survival.

The investigators concluded that the findings of the analysis confirm that the development of an effective treatment targeting HER2-low advanced gastric cancer is warranted.

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