Article
Oncology
Akihiro Ohba, Chigusa Morizane, Makoto Ueno, Satoshi Kobayashi, Yasuyuki Kawamoto, Yoshito Komatsu, Masafumi Ikeda, Mitsuhito Sasaki, Naohiro Okano, Junji Furuse, Nobuyoshi Hiraoka, Hiroshi Yoshida, Aya Kuchiba, Ryo Sadachi, Kenichi Nakamura, Naoko Matsui, Yoshiaki Nakamura, Wataru Okamoto, Takayuki Yoshino, Takuji Okusaka
Summary: Trastuzumab deruxtecan (DS-8201) has shown efficacy in HER2-positive breast and gastric cancers, and there is evidence to suggest its potential activity in HER2-positive biliary tract cancers. This article describes the rationale and design of the phase II HERB trial, which aims to evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing unresectable or recurrent biliary tract cancers.
Article
Oncology
Akihiro Ohba, Chigusa Morizane, Makoto Ueno, Satoshi Kobayashi, Yasuyuki Kawamoto, Yoshito Komatsu, Masafumi Ikeda, Mitsuhito Sasaki, Naohiro Okano, Junji Furuse, Nobuyoshi Hiraoka, Hiroshi Yoshida, Aya Kuchiba, Ryo Sadachi, Kenichi Nakamura, Naoko Matsui, Yoshiaki Nakamura, Wataru Okamoto, Takayuki Yoshino, Takuji Okusaka
Summary: Trastuzumab deruxtecan (DS-8201) is a promising new drug for HER2-positive cancers, including breast and gastric cancers. This article describes the design of a clinical trial called HERB, which aims to evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract cancers.
Review
Oncology
Jiyun Lee, Yeon Hee Park
Summary: Trastuzumab deruxtecan has demonstrated significant clinical benefits in HER2+ metastatic breast cancer patients, with an objective response rate of 60.9% and a unique side effect of pneumonitis. It has shown promising antitumor efficacy in HER2-low-expressing metastatic breast cancer. However, caution should be taken regarding the side effects, particularly lung inflammation.
Review
Oncology
Tina Nie, Hannah A. Blair
Summary: Trastuzumab deruxtecan is an approved treatment for HER2-positive breast cancer, showing superior efficacy compared to trastuzumab emtansine in a phase 3 trial. While there are common treatment-related adverse events, they are generally manageable and tolerable.
Article
Medicine, General & Internal
Shanu Modi, William Jacot, Toshinari Yamashita, Joohyuk Sohn, Maria Vidal, Eriko Tokunaga, Junji Tsurutani, Naoto T. Ueno, Aleix Prat, Yee Soo Chae, Keun Seok Lee, Naoki Niikura, Yeon Hee Park, Binghe Xu, Xiaojia Wang, Miguel Gil-Gil, Wei Li, Jean-Yves Pierga, Seock-Ah Im, Halle C. F. Moore, Hope S. Rugo, Rinat Yerushalmi, Flora Zagouri, Andrea Gombos, Sung-Bae Kim, Qiang Liu, Ting Luo, Cristina Saura, Peter Schmid, Tao Sun, Dhiraj Gambhire, Lotus Yung, Yibin Wang, Jasmeet Singh, Patrik Vitazka, Gerold Meinhardt, Nadia Harbeck, David A. Cameron
Summary: Trastuzumab deruxtecan demonstrated significantly longer progression-free and overall survival compared to physician's choice chemotherapy in patients with HER2-low metastatic breast cancer.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Preeti Narayan, Christy L. Osgood, Harpreet Singh, Haw-Jyh Chiu, Tiffany K. Ricks, Edwin Chiu Yuen Chow, Junshan Qiu, Pengfei Song, Jingyu Yu, Frances Namuswe, Maria Guiterrez-Lugo, Sherry Hou, William F. Pierce, Kirsten B. Goldberg, Shenghui Tang, Laleh Amiri-Kordestani, Marc R. Theoret, Richard Pazdur, Julia A. Beaver
Summary: On December 20, 2019, FDA granted accelerated approval to ENHERTU for the treatment of HER2-positive breast cancer based on data from DESTINY-Breast01 study. The confirmed overall response rate in 184 patients was 60.3% with a median duration of response of 14.8 months. Despite the risk of interstitial lung disease, the overall safety and efficacy data supported the accelerated approval for this indication.
CLINICAL CANCER RESEARCH
(2021)
Article
Medicine, General & Internal
Bob T. Li, Egbert F. Smit, Yasushi Goto, Kazuhiko Nakagawa, Hibiki Udagawa, Julien Mazieres, Misako Nagasaka, Lyudmila Bazhenova, Andreas N. Saltos, Enriqueta Felip, Jose M. Pacheco, Maurice Perol, Luis Paz-Ares, Kapil Saxena, Ryota Shiga, Yingkai Cheng, Suddhasatta Acharyya, Patrik Vitazka, Javad Shahidi, David Planchard, Pasi A. Janne
Summary: Trastuzumab deruxtecan demonstrated durable anticancer activity in previously treated HER2-mutant NSCLC patients, with two cases of fatal drug-related interstitial lung disease reported. The observed toxic effects were generally consistent with previous studies.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Alice Indini, Erika Rijavec, Francesco Grossi
Summary: The review highlights the significant improvement of HER2-targeted therapies in breast and gastric cancer, as well as their potential application in NSCLC and colorectal cancer, focusing on the pharmacologic characteristics, efficacy, and toxicity profile of T-DXd. The article also discusses the latest clinical trial results of T-DXd in solid tumors and ongoing research on combination therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Jiangping Yang, Jiaqi Han, Yalan Zhang, Muhelisa Muhetaer, Nianyong Chen, Xi Yan
Summary: Through cost-effectiveness analysis, we found that T-DXd is more cost-effective than T-DM1 for patients with HER2-positive metastatic breast cancer in the US, but not in China at current drug prices.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Dennis Mauricio, Stefania Bellone, Levent Mutlu, Blair McNamara, Diego D. Manavella, Cem Demirkiran, Miguel Skyler Z. Verzosa, Natalia Buza, Pei Hui, Tobias Max Philipp Hartwich, Justin Harold, Yang Yang-Hartwich, Margherita Zipponi, Gary Altwerger, Elena Ratner, Gloria S. Huang, Mitchell Clark, Vaagn Andikyan, Masoud Azodi, Peter E. Schwartz, Alessandro D. Santin
Summary: This study compared the efficacy of a novel HER2/neu-targeting antibody-drug conjugate, DS-8201a, to an ADC isotype control, MAAA-9199, against primary uterine and ovarian carcinosarcomas in vitro and in vivo. The results showed that DS-8201a was highly effective against carcinosarcoma cell lines with 3+ HER2/neu expression, but not against 0 HER2/neu cell lines. However, DS-8201a could induce efficient bystander killing of 0 HER2/neu tumor cells when mixed with 3+ HER2/neu cells. In vivo studies confirmed the superior efficacy of DS-8201a in HER2/neu-expressing carcinosarcoma xenografts.
GYNECOLOGIC ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Xoan Nguyen, Morgan Hooper, Jared Paul Borlagdan, Alison Palumbo
Summary: Fam-trastuzumab deruxtecan-nxki is an effective treatment option for HER2-positive breast cancer in advanced, unresectable, or metastatic settings. Common adverse effects include fatigue, nausea, and hair loss, while serious adverse effects such as interstitial lung disease or embryo-fetal toxicity require careful monitoring. Randomized controlled trials are still needed to further evaluate its efficacy and safety in clinical practice.
ANNALS OF PHARMACOTHERAPY
(2021)
Review
Oncology
Ioannis A. Vathiotis, Dimitrios Bafaloukos, Konstantinos N. N. Syrigos, George Samonis
Summary: Antibody-drug conjugates combine the potency of cytotoxic chemotherapy with the selectivity of targeted therapy, making them a unique and rapidly growing class of antitumor agents. This review outlines the unanswered questions and novel therapies being investigated in the treatment of HER2-mutant non-small cell lung cancer, following the approval of trastuzumab deruxtecan.
Article
Pharmacology & Pharmacy
Ophelia Yin, Yuan Xiong, Seiko Endo, Kazutaka Yoshihara, Tushar Garimella, Malaz AbuTarif, Russ Wada, Frank LaCreta
Summary: This study characterized the pharmacokinetics of Trastuzumab deruxtecan in patients with HER2-positive breast cancer or other solid tumor malignancies. Results showed no significant differences in steady-state exposure of the drug in different patient populations, suggesting that dose adjustment based on specific patient characteristics is not necessary.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
Guy Jerusalem, Yeon Hee Park, Toshinari Yamashita, Sara A. Hurvitz, Shanu Modi, Fabrice Andre, Ian E. Krop, Xavier Gonzalez Farre, Benoit You, Cristina Saura, Sung-Bae Kim, Cynthia R. Osborne, Rashmi K. Murthy, Lorenzo Gianni, Toshimi Takano, Yali Liu, Jillian Cathcart, Caleb Lee, Christophe Perrin
Summary: The DESTINY-Breast01 study evaluated the efficacy of trastuzumab deruxtecan in heavily pretreated HER2-positive metastatic breast cancer patients, and found that it showed durable clinical activity in patients with treated brain metastases.
Article
Oncology
Kyle Dunton, Gerard Vondeling, Elizabeth Hancock, Margaret Petrou, Oliver Burn, Abby Paine
Summary: This study evaluated the long-term overall survival (OS) of T-DXd in HER2+ breast cancer and compared it with other treatments. Both simulated methods showed that T-DXd had longer OS compared to eribulin and capecitabine and led to significant gains in quality-adjusted life years (QALYs).