Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu

Tymon‐Rosario, Joan; Siegel, Eric; Bellone, Stefania; Harold, Justin; Adjei, Naomi; Zeybek, Burak; Mauricio, Dennis; Altwerger, Gary; Menderes, Gulden; Ratner, Elena; Clark, Mitchell; Andikyan, Vaagn; Huang, Gloria S.; Azodi, Masoud; Schwartz, Peter E.; Fader, Amanda N.; Santin, Alessandro D.

doi:10.1016/j.ygyno.2021.07.033

Cited by 17 publications

(15 citation statements)

References 49 publications

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“…These therapeutics are routinely used for the therapy of breast [ 2 ] and gastroesophageal [ 3 ] carcinomas. HER2-targeted therapeutics are also under clinical evaluation for the treatment of ovarian [ 4 ], non-small cell lung [ 5 ], uterine [ 6 ], and urothelial [ 7 ] cancers. Accurate determination of the level of HER2 expression in tumors is a precondition for routine use and further development of such therapies.…”

Section: Introductionmentioning

confidence: 99%

Comparative Preclinical Evaluation of Peptide-Based Chelators for the Labeling of DARPin G3 with 99mTc for Radionuclide Imaging of HER2 Expression in Cancer

Ларькина

Plotnikov

Bezverkhniaia

et al. 2022

IJMS

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Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [99mTc]Tc-(HE)3-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)3), provided clear imaging of HER2 expressing breast cancer 2–4 h after injection. The goal of this study was to evaluate if the use of cysteine-containing peptide-based chelators Glu-Glu-Glu-Cys (E3C), Gly-Gly-Gly-Cys (G3C), and Gly-Gly-Gly-Ser-Cys connected via a (Gly-Gly-Gly-Ser)3-linker (designated as G3-(G3S)3C) would further improve the contrast of imaging using 99mTc-labeled derivatives of G3. The labeling of the new variants of G3 provided a radiochemical yield of over 95%. Labeled G3 variants bound specifically to human HER2-expressing cancer cell lines with affinities in the range of 1.9–5 nM. Biodistribution of [99mTc]Tc-G3-G3C, [99mTc]Tc-G3-(G3S)3C, and [99mTc]Tc-G3-E3C in mice was compared with the biodistribution of [99mTc]Tc-(HE)3-G3. It was found that the novel variants provide specific accumulation in HER2-expressing human xenografts and enable discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-(HE)3-G3 provided better contrast between tumors and the most frequent metastatic sites of HER2-expressing cancers and is therefore more suitable for clinical applications.

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Section: Introductionmentioning

confidence: 99%

Comparative Preclinical Evaluation of Peptide-Based Chelators for the Labeling of DARPin G3 with 99mTc for Radionuclide Imaging of HER2 Expression in Cancer

Ларькина

Plotnikov

Bezverkhniaia

et al. 2022

IJMS

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“…ERBB2 amplification and Her2neu overexpression has been identified in approximately 30% of uterine serous carcinomas and may be more frequent in black women [27,30]. Mutations in HER2-neu leading to over-expression of the receptor can be identified through immunohistochemistry testing, and its presence has been associated with worse survival, similar to findings in patients with breast cancer [29]. Trastuzumab is a HER2-neu monoclonal antibody, which has been shown to extend progression-free survival in advanced and recurrent HER2-positive uterine cancer [31].…”

Section: Molecular and Genomic Alterations And Targeted Therapiesmentioning

confidence: 78%

Alarming trends and disparities in high-risk endometrial cancer

Eakin

Lai

Cohen

2022

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of reviewTo summarize the most recent publications highlighting the trends and disparities among patients diagnosed with high-risk endometrial cancer.Recent findingsEndometrial cancer mortality continues to rise, driven by the increasing incidence of high-risk histologic subtypes that accounts for a disproportionate number of endometrial cancer deaths. The lack of progress made in endometrial cancer treatment, particularly of high-risk histologic subtypes, disproportionately affects black women who are more likely to be diagnosed with these aggressive tumor types. Even when accounting for high-risk histology, various factors across the spectrum of care may influence the survival disparities between black and white women, including timely access to guideline-concordant care, clinical trial enrollment, and systemic racism that impacts cancer outcomes.SummaryIn this review, we highlight the disproportionate impact of worsening endometrial cancer mortality and healthcare inequalities contributing to the endometrial cancer survival disparity between black and white women.

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“…The use of such therapeutics has become a standard of care for HER2-expressing cancers of breast [ 5 ], stomach and gastroesophageal junction [ 6 ]. Furthermore, targeting of HER2 is under clinical evaluation for therapy of carcinomas of lung [ 7 ], ovary [ 8 ] and uterus [ 9 ]. The major issues in treatment of HER2 are the possible intertumoral heterogeneous expression in the primary tumor as well as in multiple metastases [ 10 , 11 ] and the change of HER2 expression level during the courses of disease treatment [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Direct In Vivo Comparison of 99mTc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy

Tolmachev

Bodenko

Oroujeni

et al. 2022

IJMS

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Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratification of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies, thereby making treatment personalized and more efficient. Clinical evaluation in a phase I study demonstrated that injections of two scaffold protein-based imaging probes, [99mTc]Tc-(HE)3-G3 and [99mTc]Tc-ADAPT6, are safe, well-tolerated and cause a low level of radioactivity in healthy tissue. The goal of this preclinical study was to select the best probe for stratification of patients and response monitoring. Biodistribution of both tracers was compared in mice bearing SKOV-3 xenografts with high HER2 expression or MDA-MB-468 xenografts with very low expression. Changes in accumulation of the probes in SKOV-3 tumors 24 h after injection of trastuzumab were evaluated. Both [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 permitted high contrast imaging of HER2-expressing tumors and a clear discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-ADAPT6 has better preconditions for higher sensitivity and specificity of stratification. On the other hand, [99mTc]Tc-(HE)3-G3 is capable of detecting the decrease of HER2 expression on response to trastuzumab therapy only 24 h after injection of the loading dose. This indicates that the [99mTc]Tc-(HE)3-G3 tracer would be better for monitoring early response to such treatment. The results of this study should be considered in planning of further clinical development of HER2 imaging probes.

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Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu

Cited by 17 publications

References 49 publications

Comparative Preclinical Evaluation of Peptide-Based Chelators for the Labeling of DARPin G3 with 99mTc for Radionuclide Imaging of HER2 Expression in Cancer

Comparative Preclinical Evaluation of Peptide-Based Chelators for the Labeling of DARPin G3 with 99mTc for Radionuclide Imaging of HER2 Expression in Cancer

Alarming trends and disparities in high-risk endometrial cancer

Direct In Vivo Comparison of 99mTc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy

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