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)
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
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.
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.
Review
Oncology
Daisuke Kotani, Kohei Shitara
Summary: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate for HER2-positive gastric cancer, showing potential anti-tumor activities in preclinical and clinical studies. In a phase II trial, T-DXd demonstrated higher objective response rate and longer overall survival in patients with pretreated HER2-positive advanced gastric cancer.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Kenji Nakano
Summary: HER2-targeted therapies have been investigated for various malignant diseases, including osteosarcoma. However, an effective HER2-targeted therapy for osteosarcoma has not been established. The antibody-drug conjugate T-DXd showed promising efficacy in HER2-positive malignant diseases, but not in HER2-positive osteosarcoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Hiromichi Nakajima, Kenichi Harano, Tokiko Nakai, Shota Kusuhara, Takehiro Nakao, Chikako Funasaka, Chihiro Kondoh, Nobuaki Matsubara, Yoichi Naito, Ako Hosono, Shuichi Mitsunaga, Genichiro Ishii, Toru Mukohara
Summary: The study found that trastuzumab deruxtecan (T-DXd) demonstrated favorable activity in patients with HER2-positive metastatic breast cancer. Additionally, T-DXd showed meaningful benefit in patients with heterogeneity, reduction, or loss of HER2 expression.
Article
Oncology
Shanshan Hu, Yilai Wu, Jiajie Luan, Shuowen Wang, Guorong Fan
Summary: T-DXd demonstrates substantial improvement in HER2-positive metastatic breast cancer, but is not cost-effective compared to T-DM1.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Luciana de Moura Leite, Marcelle Goldner Cesca, Monique Celeste Tavares, Debora Maciel Santana, Erick Figueiredo Saldanha, Paula Tavares Guimaraes, Daniella Dias Silva Sa, Maria Fernanda Evangelista Simoes, Rafael Lima Viana, Francisca Giselle Rocha, Simone Klog Loose, Sinara Figueiredo Silva, Rafaela Pirolli, Camilla Albina Zanco Fogassa, Bruna Raphaeli Silva Mattos, Fernando Augusto Batista Campos, Solange Moraes Sanches, Vladmir Claudio Cordeiro de Lima, Noam Falbel Ponde
Summary: Our study does not support HER2-low as a biologically distinct subtype of breast cancer, showing no prognostic value on survival outcomes and no predictive effect for pathological complete response after conventional neoadjuvant chemotherapy.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Oncology
Andrea Botticelli, Roberta Caputo, Simone Scagnoli, Simona Pisegna, Michelino De Laurentiis, Giuseppe Curigliano, Matteo Lambertini, Francesco Pantano, Antonella Palazzo, Ida Paris, Claudio Vernieri, Beatrice Tedesco, Marianna Giampaglia, Michela Palleschi, Zelmira Ballatore, Daniele Alesini, Giuliana D'Auria, Agnese Fabbri, Luigi Rossi, Annarita Verrazzo, Roberta Scafetta, Daniele Marinelli, Caterina Sposetti, Vittoria Barberi, Lidia Strigari, Paolo Marchetti, Daniele Santini, Alessandra Fabi
Summary: In this multicenter retrospective study, the efficacy and safety of Trastuzumab deruxtecan (T-DXd) were confirmed in a real-world population of HER2+ metastatic breast cancer (mBC). The results are consistent with previous findings and no new safety concerns were reported.
Review
Oncology
Masahiko Aoki, Satoru Iwasa, Narikazu Boku
Summary: T-DXd, a novel HER2-targeted antibody-drug conjugate, shows high response rates and significant survival benefits in HER2-positive gastric cancer treatment, and exhibits anti-tumor activity to HER2-negative tumor cells. Its efficacy has been demonstrated in several clinical studies, indicating potential for further progress in treatment of both strongly and weakly HER2 positive gastric cancer.
Article
Biotechnology & Applied Microbiology
Saori Mishima, Kohei Shitara
Summary: T-DXd has shown significantly higher objective response rate and longer overall survival in HER2-positive AGC patients with two or more previous lines of systemic chemotherapy, including trastuzumab. Its safety profile is acceptable. Currently, there are several ongoing clinical trials of T-DXd in combination with cytotoxic chemotherapy or an immune checkpoint inhibitor.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2021)