Adjuvant Trastuzumab Emtansine (T-DM1) and Concurrent Radiotherapy for Residual Invasive HER2-positive Breast Cancer

Abstract

Objectives: The treatment of nonmetastatic HER2-positive breast cancer with residual invasive disease using concurrent Trastuzumab emtansine (T-DM1) and radiotherapy appears to be an effective option. Our aim was to evaluate the acute side effects of this treatment regime. Methods: Fourteen patients were treated between March 2019 and April 2020 concurrent T-DM1 and radiotherapy. Left ventricular ejection fraction was assessed at baseline, before and after radiotherapy. All toxicities were evaluated using Common Terminology Criteria of Adverse Events (CTCAE) version 3.0. Results: The median age was 55 years (range 36 to 72). All patients received total dose of 50 Gy for the breast/ chest wall, 10 patients got lymph node irradiation, 4 patients received an additional tumor bed boost. The most common side effect was grade 1 radiodermatitis. A reversible grade 2 left ventricular ejection fraction decrease occurred in 2 patients. During our examination 3 patients showed alanine aminotransferases increase after the cycle 4 of T-DM1, 1 patient had grade 1, 1 patient grade 2, and 1 patient grade 3 alanine aminotransferase increases. Conclusions: The acute toxicity rate especially focusing on skin and cardiac toxicity were assumed acceptable in our cohort. To safely administer this concomitant treatment, further examination and prospective data are needed.

Antibody–Drug Conjugate to Treat Meningiomas

“…Treatment with eight doses of DM1 in a three-day assay, including 0.1, 0.5, 2, 10, 30, 60, 100, and 300 nM, reduced cell viability to 24.82%, 7.09%, 6.25%, 3.32%, 2.03%, 0.83%, 0.80%, and 0.72% for CH157-MN and 26.88%, 11.12%, 7.65%, 3.99%, 2.87%, 2.05%, 1.84%, and 1.37% for AC07 ( Figure 3 A). The calculated IC 50 value of DM1 was 0.31 nM for CH157-MN and 0.56 nM for AC07, which confirmed that DM1 is a highly potent cytotoxin without cancer or tumor cell selectivity [ 30 , 31 ]. Treatment with nine doses of ADC, including 0.5, 1, 2, 10, 25, 50, 100, 250, and 500 nM, decreased the final viability of CH157-MN to 95.70%, 96.48%, 96.30%, 41.26%, 18.90%, 11.80%, 10.35%, 7.96%, and 2.67% ( Figure 3 A) with an IC 50 of 7.41 nM.…”

“…Antibody–drug conjugates (ADCs) have been developed to treat cancers or tumors [ 19 , 20 , 21 , 22 ] and have demonstrated promising clinical efficacy and minimal adverse effects [ 23 , 24 , 25 , 26 ]. For instance, the gemtuzumab ozogamicin (anti-CD33 mAb-N-acetyl gamma calicheamicin conjugate) [ 27 , 28 ] for acute myeloid leukemia treatment, traztuzumab deruxtecan (anti-HER2 mAb-topoisomerase I inhibitor) [ 29 ] and trastuzumab emtansine (anti-HER2 mAb-Mertansine DM1 conjugate) [ 30 , 31 ] for chemotherapy refractory or advanced HER2-positive breast cancer, brentuximab vedotin (anti-CD30 mAb-MMAE conjugate) [ 32 , 33 ] for relapsed Hodgkin lymphoma, and 131 I-Tositumomab (anti-CD20 mAb-Iodine 131) [ 34 ] and 90 Y-Ibritumomab tiuxetan (anti-CD20 mAb-Yttrium-90) [ 35 ] for non-Hodgkin lymphoma have been approved by the FDA and used in clinics. Compared to standard chemotherapies, ADCs can specifically target cancer cells, deliver highly cytotoxic payloads, and reduce adverse effects.…”

“…The objective of this study was to develop and evaluate an ADC-based targeted therapy to treat aggressive meningiomas overexpressing SSTR2. Our mAb that targets the extracellular domain of surface SSTR2 was produced in fed-batch culture, purified using liquid chromatography, and conjugated with an FDA-approved potent payload, mertansine (DM1), which inhibits the polymerization of microtubules and cell proliferation [ 30 , 31 , 38 ]. The meningioma-specific targeting, pharmacokinetics, toxicity, and anti-tumor efficacy of the constructed ADC were evaluated in vitro using cell lines or in vivo using an intracranial xenograft mouse model.…”

Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management

“…To our knowledge, no in vivo study was currently published on this subject. Zolcsák et al have also recently reported in a retrospective study of 14 patients that TDM-1 concomitantly administered with locoregional RT was well supported, without high-grade cardiac toxicity [ 43 ]. Of course, these results were obtained using a small number of subjects, and a validation cohort would be necessary to confirm these results.…”

Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies

“…The majority of existing data is when T-DM1 is combined with conventionally fractionated RT [129][130][131][132][133] . Sideeffects reported in this setting are minimal (radiation dermatitis, pneumonitis and cardiac toxicities) and safety has been reported when administrated with concurrent RT in a recent systemic review 134 .…”