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ABSTRACT Objective Human epidermal growth factor receptor 2 (HER2) overexpression occurs in up to 30% of breast cancer cases. Ado-trastuzumab emtansine (T-DM1) is approved to treat residual HER2-positive breast cancer after neoadjuvant therapy. The aim of this study was to determine the quality-adjusted time with symptoms or toxicity and without symptoms or toxicity (Q-TWiST) of T-DM1 compared to trastuzumab for residual invasive HER2-positive breast cancer. Methods The authors developed an analytical model extracting individual patient data and estimated invasive disease-free survival and overall survival over a 30-year time horizon. Only direct costs from adjuvant treatment were considered as well as relapse treatment from Brazilian and American payer perspectives. Heart events were considered for utility and cost analysis. Results The 30-year projection utilizing the Weibull method estimated a mean invasive disease-free survival of 16.4 years for T-DM1 and 10.4 for Trastuzumab, in addition to a mean overall survival of 18.1 and 15.4 years, respectively. We determined a Q-TWiST gain of 3,812 years for the T-DM1 arm when compared to trastuzumab and an Incremental cost-effectiveness ratio per Q-TWiST of US$ 11,467.65 in the United States and US$ 3,332.73 in Brazil. Conclusion Ado-trastuzumab emtansine is cost-effective from both Brazilian and American perspectives.
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OBJECTIVE To analyze the adverse drug reaction （ADR）signals of ado-trastuzumab emtansine and brentuximab vedotin，so as to provide reference for clinical medication safety. METHODS Using the FDA adverse drug event reporting system （FAERS）database and OpenVigil 2.1 data platform ，the ADR of the two drugs were collected from being approved by FDA to the Sep. 30th，2021. The ADR signals were detected by frequency method and sorted according to the occurrence frequency and signal strength respectively. RESULTS & CONCLUSIONS A total of 2 319 and 3 178 ADR reports related to ado-trastuzumab emtansine and brentuximab vedotin were collected ，215 and 329 ADR signals were detected respectively. According to the occurrence frequency，the most frequent ADR s of the two drugs were thrombocytopenia （109 cases）and febrile neutropenia （198 cases）， separately，which were consistent with the drug instructions. According to the signal strength ，the spider nevus of ado-trastuzumab emtansine（report odds ratio of 451.46）and the noninfectious endocarditis of brentuximab vedotin （report odds ratio of 304.35） ranked first ，both of which were not reported in the drug instructions. It is suggested that attention should be paid not only to the most common ADR s of blood and lymphatic system caused by both drugs ，but also to the ADRs not reported in the drug instructions such as spider nevus of ado-trastuzumab emtansine and noninfective endocarditis of brentuximab vedotin.
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Introducción: El tratamiento neodyuvante del cáncer de mama HER2 positivo ha ido evolucionando a través del tiempo, con la implementación de nuevas estrategias de manejo terapéutico. Es de esta manera como el trastuzumab, un anticuerpo monoclonal anti-HER2sigue siendo el tratamiento estándar en este subtipo de cáncer, los primeros estudios en los que se evidencia su eficacia son el realizado por el Dr. Buzdar y el estudio NOAH en los cuales las pacientes alcanzaron mayores tasas de respuesta patológica completa en comparación con quimioterapia sola, así como también un mayor número de cirugías conservadoras de mama en lugar de mastectomía.Con el paso de los años se han ido desarrollando nuevas estrategias de manejo terapéutico, así tenemos el doble bloqueo anti-HER2 con los anticuerpos monoclonales trastuzumab y pertuzumab que han mejorado las tasas de respuesta patológica completa. Además se ha incluido al lapatinib un inhibidor de tirosina quinasa como parte de las terapias dirigidas. Se ha dilucidado si las antraciclinas confieren un beneficio adicional al tratamiento neoadyuvante y los estudios demuestran que el beneficio es el mismo queotros esquemas de quimioterapia. Es en realidad la quimioterapia indispensable en la neoadyuvancia, el estudio PHERGain demuestra que existen pacientes que pueden alcanzar respuesta patológica completa solo con el doble bloqueo anti-her2 (trastuzumab y pertuzumab) lo que evitaría la toxicidad innecesaria por quimioterapia, y se podrían desarrollar estrategias para el manejo de aquellas pacientes que no alcanzaron una respuestapatológica completa posterior al doble bloqueo. Aún queda un campo amplio por explorar y con estudios en curso al momento. Palabras claves:DsCS:Receptor ErbB-2, Trastuzumab, Neoplasias de la Mama, Quimioterapia Adyuvante, Ado-Trastuzumab Emtansina
Introduction:The neodyuvanttreatment of HER2 positive breast cancer has evolved over time, with the implementation of new therapeutic management strategies. It is in this way that trastuzumab, an anti-HER2 monoclonal antibody continues to be the standard treatment in this subtype of cancer, the first studies in which its efficacy is evidenced are the one carried out by Dr. Buzdar and the NOAH study in which patients achieved higher rates of complete pathological response compared to chemotherapy alone, as well as a higher number of breast-conserving surgeries rather than mastectomy.Over the years, new therapeutic management strategies have been developed, thus we have the double anti-HER2 blockade with the monoclonal antibodies trastuzumab and pertuzumab that have improved the ratesof complete pathological response. In addition, lapatinib, a tyrosine kinase inhibitor, has been included as part of targeted therapies. It has been elucidated whether anthracyclines confer an additional benefit to neoadjuvant treatment and studies show that the benefit is the same as other chemotherapy regimens.It is actually the essential chemotherapy in neoadjuvant therapy, the PHERGain study shows that there are patients who can achieve a complete pathological response only with the double anti-her2 blockade (trastuzumab and pertuzumab), which would avoid unnecessary toxicity due to chemotherapy, and strategies could be developed for the management of those patients who did not achieve a complete pathological response after double blockade. There is still a wide field to explore and with studies underway at the moment. Keywords:MESH:Receptor, ErbB-2;Trastuzumab; Breast Neoplasms; Chemotherapy, Adjuvant; Ado-Trastuzumab Emtansine
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Humans , Breast Neoplasms , Receptor, ErbB-2 , Trastuzumab , Chemotherapy, Adjuvant , Ado-Trastuzumab EmtansineABSTRACT
As a new design strategy of anticancer drugs, antibody-drug conjugates have become a research hotspot in recent years. In 2013, the successful launch of ado trastuzumab emtansine(Kadcyla) provided a new solution for second-line treatment with trastuzumab-resistant HER2-positive advanced breast cancer patients. Based on its excellent clinical performance and HER2‘s overexpressing in many tumors, Roche further attempts to expand it for the therapy of HER2-positive metastatic breast cancer of each line and neoadjuvant for early breast cancer treatment, as well as applications to gastric cancer and non-small cell lung cancer(NSCLC) treatment. In general, results are mixed. Its position as second-line drugs of is further established, but factors such as tumor heterogeneity are still a big challenge. This paper reviews the recent progress in these areas after its launch.
ABSTRACT
As a new design strategy of anticancer drugs,antibody-drug conjugates have become a research hotspot in recent years. In 2013,the successful launch of ado trastuzumab emtansine(Kadcyla)provided a new solution for second-line treatment with trastuzumab-resistant HER2-positive advanced breast cancer patients. Based on its excellent clinical performance and HER2′s overex?pressing in many tumors,Roche further attempts to expand it for the therapy of HER2-positive metastatic breast cancer of each line and neoadjuvant for early breast cancer treatment,as well as applications to gastric cancer and non-small cell lung cancer(NSCLC) treatment. In general,results are mixed. Its position as second-line drugs of is further established,but factors such as tumor heteroge?neity are still a big challenge. This paper reviews the recent progress in these areas after its launch.