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
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
G. Curigliano, V Mueller, V Borges, E. Hamilton, S. Hurvitz, S. Loi, R. Murthy, A. Okines, E. Paplomata, D. Cameron, L. A. Carey, K. Gelmon, G. N. Hortobagyi, I Krop, S. Loibl, M. Pegram, D. Slamon, J. Ramos, W. Feng, E. Winer
Summary: In patients with HER2+ metastatic breast cancer, the combination of tucatinib, trastuzumab, and capecitabine provides a clinically significant improvement in overall survival and progression-free survival.
ANNALS OF ONCOLOGY
(2022)
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
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
Oncology
Kohei Shitara, Kensei Yamaguchi, Kei Muro, Hisateru Yasui, Daisuke Sakai, Takashi Oshima, Masahiro Fujimura, Yuta Sato, Shunsuke Yamazaki, Tatsuya Wakabayashi, Masahiro Sugihara, Takahiro Kamio, Hirokazu Shoji
Summary: This expanded-access study aimed to provide T-DXd treatment to previously treated patients with HER2-positive gastric or gastroesophageal junction adenocarcinomas in Japan. The study showed that T-DXd had a good safety profile.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2023)
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)
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
Oncology
Mirat Shah, Suparna Wedam, Joyce Cheng, Mallorie H. Fiero, Huiming Xia, Fang Li, Jianghong Fan, Xinyuan Zhang, Jingyu Yu, Pengfei Song, Wei Chen, Tiffany K. Ricks, Xiao Hong Chen, Kirsten B. Goldberg, Yutao Gong, William F. Pierce, Shenghui Tang, Marc R. Theoret, Richard Pazdur, Laleh Amiri-Kordestani, Julia A. Beaver
Summary: Tucatinib in combination with trastuzumab and capecitabine was approved by the FDA for the treatment of advanced HER2-positive breast cancer, with demonstrated efficacy in patients with brain metastases. The approval was based on data from the HER2CLIMB trial showing significant benefit in progression-free survival and overall survival.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Jose Manuel Perez-Garcia, Marta Vaz Batista, Patricia Cortez, Manuel Ruiz-Borrego, Juan Miguel Cejalvo, Juan de la Haba-rodriguez, Laia Garrigos, Fabricio Racca, Sonia Servitja, Salvador Blanch, Maria Gion, Monica Nave, Maria Fernandez-Abad, Alejandro Martinez-Bueno, Antonio Llombart-Cussac, Miguel Sampayo-Cordero, Andrea Malfettone, Javier Cortes, Sofia Braga
Summary: The DEBBRAH study aimed to evaluate the efficacy of T-DXd in patients with HER2-positive or HER2-low breast cancer, and found that T-DXd showed favorable intracranial activity and tolerability in patients with stable, untreated, or progressing brain metastases.
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
John H. Strickler, Andrea Cercek, Salvatore Siena, Thierry Andre, Kimmie Ng, Eric Van Cutsem, Christina Wu, Andrew S. Paulson, Joleen M. Hubbard, Andrew L. Coveler, Christos Fountzilas, Adel Kardosh, Pashtoon M. Kasi, Heinz-Josef Lenz, Kristen K. Ciombor, Elena Elez, David L. Bajor, Chiara Cremolini, Federico Sanchez, Michael Stecher, Wentao Feng, Tanios S. Bekaii-Saab
Summary: Tucatinib plus trastuzumab demonstrated clinically meaningful anti-tumor activity and favorable tolerability in patients with chemotherapy-refractory, HER2-positive metastatic colorectal cancer. It represents an important new treatment option for this patient population.
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.
Article
Oncology
Toru Mukohara, Ako Hosono, Sachiyo Mimaki, Akiko Nakayama, Shota Kusuhara, Chikako Funasaka, Takehiro Nakao, Yoko Fukasawa, Chihiro Kondoh, Kenichi Harano, Yoichi Naito, Nobuaki Matsubara, Katsuya Tsuchihara, Takeshi Kuwata
Summary: Mutations in the HER2 gene play a role in resistance to anti-HER2 therapies, but co-occurrence of HER2 mutation and amplification is rare. A breast cancer patient with both HER2 amplification and the L755S mutation displayed clinical resistance to standard trastuzumab or lapatinib therapies, but showed good responses to T-DM1 and T-DXd. Anti-HER2 ADCs may be preferred over conventional therapies for patients with HER2-amplified and comutated tumors.
Review
Oncology
G. Antonarelli, C. Corti, B. T. Salimbeni, P. Tarantino, P. Zagami, A. Marra, D. Trapani, S. Tolaney, J. Cortes, G. Curigliano
Summary: The introduction of antibody-drug conjugates (ADCs) has greatly impacted the treatment of patients with HER2-positive advanced breast cancer (ABC) in the past decade. ADCs have the ability to deliver toxic chemotherapeutics to tumor sites by utilizing monoclonal antibodies. Two different ADCs, trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have already been used in clinical practice for HER2-positive ABC treatment, with T-DXd showing better survival outcomes. However, there is still a clinical controversy regarding treatment decisions and benefits following T-DXd. The field of breast cancer research is rapidly changing with the development of novel ADC formulations, and addressing T-DXd resistance is a priority.
