2P - Outcomes of patients with gynecological tumors harboring HER2 defects: a single center study based on Gustave Roussy cancer center’s molecular program

Background

Human epidermal growth factor 2 (HER2) encoded by the ERBB2 gene. In serous endometrial carcinoma (SEC), HER2 is amplified in 17-30% cases. ERBB2 alterations are also present across other gynecological histologies. A randomized phase II study showed that the addition of trastuzumab to 1^st line platinum chemotherapy increased PFS and OS in HER2 amplified SEC, yet there is currently no approval for those drugs in gynecological malignancies.

Methods

We retrospectively collected data from patients with gynecological cancers who were screened by next generation sequencing (NGS) on tumor and/or circulating tumor DNA (ctDNA) and discussed at Gustave Roussy’s molecular tumor board between March 2021 and June 2022. The objective of this study was to describe the outcomes of gynecological patients harboring HER2 amplifications or pathogenic mutations that were identified through Gustave Roussy’s molecular program.

Results

Between March 2021 and June 2022, 19 patients had a HER2 amplification and/or mutation. 11 patients (58%) exhibited an amplification, 6 (32%) a mutation and 2 (10%) both. All patients had metastatic disease at the time of screening. Regarding tumor types: 10 patients (53%) had endometrial carcinoma, 5 (26%) had ovarian carcinoma and 4 (21%) had cervix carcinoma. Only 9 patients (47%) received a HER2 directed therapy. All patient had ERBB2 amplification. 1 patient was treated within a trial and 8 were treated off label with a trastuzumab containing regimen. 2 patients (22%) had a complete response and 5 (55%) had a partial response. Median duration of response was 7,6 months and median progression free survival was 8.1 month [min : 2.6m; max:11.6m]. Overall survival was significantly longer in patients receiving HER2 targeted therapy compared to those harboring HER2 abnormalities who did not receive them (mOS: NR vs 15.06m, HR : 0.18, IC95% 0.037 - 0.89).

Conclusions

Gynecological cancer harboring HER2 amplification and/or mutation are rare but can benefit from HER2 targeted therapy. There is a need to to test patients for ERBB2 alteration and develop trials with HER2 targeted therapies including gynecological tumors in order to obtain approvals in routine care.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.