Second line trastuzumab emtansine following horizontal dual blockade in a real-life setting
ABSTRACT
Despite relevant medical advancements, metastatic breast cancer remains an uncurable disease. HER2 signaling conditions tumor behavior and treatment strategies of HER2 expressing breast cancer. Cancer treatment guidelines uniformly identify dual blockade with pertuzumab and trastuzumab plus a taxane as best first line and trastuzumab emtansine as preferred second line choice. However, there is no prospectively designed available study focusing on the sequence and outcomes of patients treated with T-DM1 following the triplet. In the following report, data concerning a wide series of patients treated in a real-life setting are presented. Results obtained in terms of response and median progression free survival suggests a significant role for T-DM1 in disease control of metastatic HER2 expressing breast cancer.
INTRODUCTION
From 80s, Human Epidermal Growth Factor Receptor 2 (HER2) signaling was increasingly recognized as pivotal in tumor growth of HER2 expressing breast cancer. HER2 expression is limited to a proportion (15–20%) of breast cancer; however, HER2 conditions tumor behavior and addresses treatment strategies. Current available guidelines in metastatic HER2 positive breast cancer designs a sequence of treatment with first-line double blockade with trastuzumab plus pertuzumab and a taxane according to Cleopatra trial results [1] and second-line treatment with trastuzumab emtansine (T-DM1) enforced by Emilia trial results [2] and, then, lapatinib plus capecitabine [3].
T-DM1 is an antibody-drug conjugate, which drives the chemotherapeutic maytansine directly to HER2 expressing cells through the driver trastuzumab [4]. The development of drugs like T-DM1 arise from the concept of increasing drug concentration at the tumor and mitigated toxicity due to drug deliver at the site of HER2 expressing tumor cells. Therapy with antibody-drug conjugates is a tempting strategy especially in later lines of treatment as showed by recent results with trastuzumab deruxtecan (DS-8201) [5]. Since T-DM1 introduction in clinical practice in second-line, overall survival has reached 30.9 months [2]. The reduced toxicity of T-DM1 in second and later lines of treatment together and the high rates of activity and efficacy [2] are determinant in choosing treatment for a patient candidate to a prolonged time on treatment. On February 22, 2013, the Food and Drug Administration (FDA) approved T-DM1 for use as a single agent in the treatment of patients with HER2-positive metastatic breast cancer who previously received trastuzumab and a taxane [6]. In 2019, the KATHERINE trial showed a significant benefit of adjuvant T-DM1 in HER2-positive patients treated with neoadjuvant treatment and not achieving a pathologic complete response [7]. In fact, these patients showed with adjuvant T-DM1 a risk of recurrence 50% lower than with trastuzumab alone. Such results induced FDA on May 3, 2019 to approve T-DM1 for the adjuvant treatment of patients with HER2-positive early breast cancer treated with neoadjuvant taxane and trastuzumab-based treatment and having residual invasive disease in the breast or axilla at surgery [8]. In Italy, T-DM1 is authorized in this setting on an individual basis in the context of a compassionate use. https://www.oncotarget.com/article/27603/text/
When general population mention today’s medicine, accuracy plays one of the most significant roles and human lives are directly dependent on it. Hence, any researches pertaining to medicine are required to comply with the top standards. The challenge nowadays is that any outcomes of researches can be published online and used as a reference without being adequately checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this issue and attempted to develop an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been established back in 2010. The main principle of this journal is related to Altmetric scores that are used as a quality measure. That allows both readers and authors to quality-check publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a full publications list with corresponding scores above 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it provides the necessary assistance to anyone, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was published back in 2018 by Oncotarget and completed by several experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and provides an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The article has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are willing to comprehend the very meaning of it. Based on the Altmetric website, the score relates to “how many people have been exposed to and engaged with a scholarly output.” Hereby, the article about melanoma, was used for citations in different news articles 69 times. Moreover, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their news on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This study has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive useful scientific facts. Oncotarget is happy to have the chance to share with online readers this highly appreciated and high-quality information, that is trustworthy and reliable.
When public mention modern medicine, accuracy plays one of the most significant roles and people’s lives are directly dependent on it. Hence, any researches related to medicine are necessary to comply with the highest standards. The problem nowadays is that any conclusions of researches can be published online and used as a reference without being precisely verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this problem and tried to generate an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been founded back in 2010. The main principle of this journal is based on Altmetric scores that are used as a quality measure. That assists both readers and authors to verify publications with Altmetric Article Reports that provide “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a full publications list with respective scores above 100 as well as reports mentioned above. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it creates the necessary help to anyone, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was published back in 2018 by Oncotarget and written by several experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study mentions that “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and provides an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The article has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are willing to understand the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Hence, the article about melanoma, was used for citations in different news articles 69 times. In addition, it was referred to in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
Another Oncotarget’s research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This publication has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a short overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is glad to have the chance to share with online readers this highly appreciated and top-quality information, that is trustworthy and reliable.
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