A Systematic Review and Pooled Analysis of Studies of Oral Etoposide in Metastatic Breast Cancer

Voutsadakis, Ioannis A.

doi:10.5152/ejbh.2017.3563

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…In a prospective phase II study [42], a median PFS of 4.5 months was reported in 75 patients with MBC and a median number of 2 prior lines of therapy, of which 22 had an HER2+ disease. A review of twelve studies, of which HER2+ MBC patients comprised about a third, reported an overall 18.5% response rate with oral VP16 [43]. None of these studies specified the use of anti-HER2 therapy in combination with oral VP16.…”

Section: Discussionmentioning

confidence: 99%

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

Chalumeau

Carton

Eeckhoutte

et al. 2022

Cancers

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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.

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Section: Discussionmentioning

confidence: 99%

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

Chalumeau

Carton

Eeckhoutte

et al. 2022

Cancers

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“…Thus, it may be meaningful to verify if etoposide upregulates CD82 expression in breast cancer patients, for repurposing as a therapeutic agent in treating a subset of non-metastatic breast cancer patients with low CD82 expression. This is especially since etoposide at a low dose is preferred by some clinicians because of its relatively lower cost compared to other chemotherapeutic drugs and oral route of administration (thereby avoiding visits to the clinic for drug infusions) [97].…”

Section: Drugs Known To Target Cd82 Tyrosine Kinase Inhibitors (Tkis)mentioning

confidence: 99%

Targeting CD82/KAI1 for Precision Therapeutics in Surmounting Metastatic Potential in Breast Cancer

Viera

Yip

Shen

et al. 2021

Cancers

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Metastasis is the main cause of mortality in breast cancer patients. There is an unmet need to develop therapies that can impede metastatic spread. Precision oncology has shown great promise for the treatment of cancers, as the therapeutic approach is tailored to a specific group of patients who are likely to benefit from the treatment, rather than the traditional approach of “one size fits all”. CD82, also known as KAI1, a glycoprotein belonging to the tetraspanin family and an established metastasis suppressor, could potentially be exploited to hinder metastases in breast cancer. This review explores the prospect of targeting CD82 as an innovative therapeutic approach in precision medicine for breast cancer patients, with the goal of preventing cancer progression and metastasis. Such an approach would entail the selection of a subset of breast cancer patients with low levels of CD82, and instituting an appropriate treatment scheme tailored towards restoring the levels of CD82 in this group of patients. Proposed precision treatment regimens include current modalities of treating breast cancer, in combination with either clinically approved drugs that could restore the levels of CD82, CD82 peptide mimics or non-coding RNA-based therapeutics.

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“…In a prospective phase II study (46), a median PFS of 4.5 months as reported in 75 patients with MBC and a median number of 2 prior lines of therapy, of which 22 had an HER2 + disease. A review of twelve studies, including about a third of HER2 + MBC patients, reported an overall 18.5% response rate with oral VP16 (47). None of these studies speci ed the use of anti-HER2 therapy in combination with oral VP16.…”

Section: Discussionmentioning

confidence: 99%

Oral etoposide and trastuzumab in HER2-positive metastatic breast cancer: a retrospective study at Institut Curie Hospitals.

Lerebours

Chalumeau

Carton

et al. 2022

Preprint

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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). However, the clinical benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not been evaluated.Methods: Patients treated at Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in-silico search. Trained medical oncologists retrospectively assessed progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as a duration of at least 6 months), 6 months clinical benefit rate and toxicity. 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%) had a clinical benefit. Only 3 patients stopped treatment for toxicity. Median PFS in the population with and without TOP2A/ERBB2 co-amplification was respectively 4.7 months (95% CI [2.3-NA]) and 2.9 months (95% CI [1.2-NA]; p=0.36).Conclusion: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC.

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A Systematic Review and Pooled Analysis of Studies of Oral Etoposide in Metastatic Breast Cancer

Cited by 8 publications

References 25 publications

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

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

Targeting CD82/KAI1 for Precision Therapeutics in Surmounting Metastatic Potential in Breast Cancer

Oral etoposide and trastuzumab in HER2-positive metastatic breast cancer: a retrospective study at Institut Curie Hospitals.

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