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. 2022 Apr 24;14(9):2114.
doi: 10.3390/cancers14092114.

Oral Etoposide and Trastuzumab Use for HER2-Positive Metastatic Breast Cancer: A Retrospective Study from the Institut Curie Hospitals

Clelia Chalumeau  1 , Matthieu Carton  2 , Alexandre Eeckhoutte  3   4 , Stelly Ballet  5 , Anne Vincent-Salomon  5 , Perrine Vuagnat  1 , Audrey Bellesoeur  6 , Jean-Yves Pierga  6   7 , Marc-Henri Stern  3   4 , Francois-Clement Bidard  1   8 , Florence Lerebours  1
Affiliations

Oral Etoposide and Trastuzumab Use for HER2-Positive Metastatic Breast Cancer: A Retrospective Study from the Institut Curie Hospitals

Clelia Chalumeau et al. Cancers (Basel). .

Abstract

Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been evaluated.

Methods: Patients treated at the Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in silico search. Progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as at least 6 months), clinical benefit, and toxicity were assessed. The co-amplification of ERBB2 and TOP2A was assessed by shallow whole genome sequencing on tumor tissue whenever available.

Results: Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4-4.7]) and 11.3 months (95% CI [8.3-25.0]), respectively. Three patients had a complete response, while 12/40 (30%) experienced clinical benefit. Only three patients stopped treatment for toxicity. Seven (35%) patients displayed a TOP2A/ERBB2 co-amplification. No statistically significant correlation was found between outcome and TOP2A/ERBB2 co-amplification.

Conclusion: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC.

Keywords: HER2 metastatic breast cancer; TOP2A/ERBB2 co-amplification; oral etoposide; trastuzumab.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier estimates of progression-free survival (A) and overall survival (B) in patients treated with VP16-T.
Figure 2
Figure 2
PFS by patient in relation to prior treatment lines and VP16-T. Clinical benefit was defined by either an objective tumor response (n = 4 patients) and/or a PFS under VP16-T for longer than 6 months (n = 8 patients).
Figure 3
Figure 3
PFS depending on TOP2A/ERBB2 co-amplification status.
See this image and copyright information in PMC

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