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
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
Salvatore Siena, Maria Di Bartolomeo, Kanwal Raghav, Toshiki Masuishi, Fotios Loupakis, Hisato Kawakami, Kensei Yamaguchi, Tomohiro Nishina, Marwan Fakih, Elena Elez, Javier Rodriguez, Fortunato Ciardiello, Yoshito Komatsu, Taito Esaki, Ki Chung, Zev Wainberg, Andrea Sartore-Bianchi, Kapil Saxena, Eriko Yamamoto, Emarjola Bako, Yasuyuki Okuda, Javad Shahidi, Axel Grothey, Takayuki Yoshino
Summary: This study aimed to investigate the antitumour activity and safety of trastuzurnab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. The drug showed promising and durable activity in HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with previous trials. However, careful monitoring and prompt intervention are required for important risks like interstitial lung disease and pneumonitis.
Article
Oncology
Koichi Goto, Yasushi Goto, Toshio Kubo, Kiichiro Ninomiya, Sang-We Kim, David Planchard, Myung-Ju Ahn, Egbert F. Smit, Adrianus Johannes de Langen, Maurice Perol, Elvire Pons-Tostivint, Silvia Novello, Hidetoshi Hayashi, Junichi Shimizu, Dong-Wan Kim, Chih-Hsi Kuo, James Chih-Hsin Yang, Kaline Pereira, Fu-Chih Cheng, Ayumi Taguchi, Yingkai Cheng, Wenqin Feng, Zenta Tsuchihashi, Pasi A. Janne
Summary: T-DXd demonstrates clinically meaningful responses in patients with previously treated HER2-positive non-small-cell lung cancer, with favorable safety at a dosage of 5.4 mg/kg.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
G. Curigliano, K. Dunton, M. Rosenlund, M. Janek, J. Cathcart, Y. Liu, P. A. Fasching, H. Iwata
Summary: In the DESTINY-Breast03 clinical trial, trastuzumab deruxtecan (T-DXd) showed superior efficacy and safety compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. Patient-reported outcomes (PROs) and hospitalization data were analyzed, demonstrating that T-DXd may delay time until health-related quality of life deterioration and resulted in longer time to first hospitalization compared to T-DM1.
ANNALS OF ONCOLOGY
(2023)
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.
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.
Article
Medicine, General & Internal
Sara A. Hurvitz, Roberto Hegg, Wei-Pang Chung, Seock-Ah Im, William Jacot, Vinod Ganju, Joanne Wing Yan Chiu, Binghe Xu, Erika Hamilton, Srinivasan Madhusudan, Hiroji Iwata, Sevilay Altintas, Jan-Willem Henning, Giuseppe Curigliano, Jose Manuel Perez-Garcia, Sung-Bae Kim, Vanessa Petry, Chiun-Sheng Huang, Wei Li, Jean-Sebastien Frenel, Silvia Antolin, Winnie Yeo, Giampaolo Bianchini, Sherene Loi, Junji Tsurutani, Anton Egorov, Yali Liu, Jillian Cathcart, Shahid Ashfaque, Javier Cortes
Summary: In the DESTINY-Breast03 trial, trastuzumab deruxtecan showed superior progression-free survival compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer. The study aimed to compare the efficacy and safety of trastuzumab deruxtecan versus trastuzumab emtansine. The results demonstrated that trastuzumab deruxtecan had the longest reported median progression-free survival and improved overall survival, reaffirming its role as the standard of care in the second-line setting.
Article
Oncology
Shanu Modi
Summary: The article summarizes the results of the DESTINY-Breast01 study, which showed that T-DXd treatment reduced tumor growth in HER2-positive breast cancer patients, with over 60% of patients experiencing tumor shrinkage or disappearance for nearly 15 months on average.
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.
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
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
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.
Article
Oncology
Liu Yang, Wenfei Li, Zhihao Lu, Ming Lu, Jun Zhou, Zhi Peng, Xiaotian Zhang, Xicheng Wang, Lin Shen, Jian Li
Summary: Gender and resection of primary lesions may be independent prognostic factors for advanced HER2 positive colorectal cancer patients. Patients with HER2-positive mCRC receiving chemotherapy combined with trastuzumab have better efficacy than those without trastuzumab.
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
Tetsuji Terazawa, Takeshi Kato, Masahiro Goto, Katsuya Ohta, Hironaga Satake, Shingo Noura, Yoshinori Kagawa, Hisato Kawakami, Hiroko Hasegawa, Kazuhiro Yanagihara, Tatsushi Shingai, Ken Nakata, Masahito Kotaka, Masayuki Hiraki, Ken Konishi, Shiro Nakae, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Toshimasa Tsujinaka, Taroh Satoh
Summary: This study aimed to investigate the efficacy of panitumumab in patients with RAS wild-type colorectal cancer. The results showed that panitumumab demonstrated favorable overall survival in frail or elderly patients without prior exposure to chemotherapy, with a more significant effect observed in patients with left-sided tumors.
Article
Oncology
Jun Watanabe, Tetsuji Terazawa, Shiho Yamane, Hirotaka Kazama, Hiroyuki Uetake, Takayuki Yoshino
Summary: This study evaluated the safety and effectiveness of aflibercept with 5-fluorouracil/levofolinate/irinotecan in Japanese patients with mCRC in a real-world clinical setting. The results showed that there were no new risks associated with aflibercept and its effectiveness in second-line treatment was consistent with previous reports.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Kanwal Raghav, Fang-Shu Ou, Alan P. Venook, Federico Innocenti, Ryan Sun, Heinz-Josef Lenz, Scott Kopetz
Summary: Clinical trial updates allow for dissemination of additional results from studies where the primary end point has already been reported. This study aimed to determine the prevalence of acquired genomic alterations (Acq-GAs) on anti-EGFR-chemotherapy compared to anti-VEGF-chemotherapy and later-line anti-EGFR-antibody therapy in metastatic colorectal cancer (mCRC). The findings indicate divergent resistance mechanisms with rare occurrence of Acq-GAs with up-front use of anti-EGFR-chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Kanwal P. S. Raghav, Mark M. Moasser
CLINICAL CANCER RESEARCH
(2023)
Review
Gastroenterology & Hepatology
Hideaki Bando, Atsushi Ohtsu, Takayuki Yoshino
Summary: In the era of targeted therapy based on genomic alterations, the treatment strategy for metastatic colorectal cancer (mCRC) is undergoing changes. Determining the genomic status of specific alterations such as KRAS and NRAS, BRAF(V600E) mutations, ERBB2, and microsatellite instability and/or mismatch repair (MMR) status is recommended before starting systemic treatment. Trials have shown the efficacy of pembrolizumab as first-line therapy and the combination of encorafenib and cetuximab as second-line or third-line therapy in patients with deficient MMR and BRAF(V600E) mCRC. New agents are also being developed for rare molecular fractions such as ERBB2 alterations and KRAS(G12C) mutations.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Seiichiro Mitani, Hiasto Kawakami, Osamu Shiraishi, Hiroaki Kanemura, Shinichiro Suzuki, Koji Haratani, Hidetoshi Hayashi, Kimio Yonesaka, Yasutaka Chiba, Takushi Yasuda, Kazuhiko Nakagawa
Summary: In patients with resectable esophageal squamous cell carcinoma, the alteration of PD-L1 expression before and after neoadjuvant chemotherapy was found to be related to clinical outcomes.
Correction
Gastroenterology & Hepatology
Seiichiro Mitani, Hisato Kawakami, Osamu Shiraishi, Hiroaki Kanemura, Shinichiro Suzuki, Koji Haratani, Hidetoshi Hayashi, Kimio Yonesaka, Yasutaka Chiba, Takushi Yasuda, Kazuhiko Nakagawa
Article
Oncology
Daichi Kitaguchi, Yuichiro Tsukada, Masaaki Ito, Satoshi Horasawa, Hideaki Bando, Takayuki Yoshino, Kazutaka Yamada, Yoichi Ajioka, Kenichi Sugihara
Summary: This study investigated the survival outcomes of salvage abdominoperineal resection (APR) for recurrent and persistent diseases in squamous cell carcinoma of the anus (SCCA) patients who experienced locoregional failure after chemoradiotherapy. The results showed that salvage APR had significantly higher overall survival for recurrent disease compared to non-salvage APR, but there was no significant difference for persistent disease. The study highlights the importance of distinguishing between recurrent and persistent diseases in determining the appropriate treatment strategy.
Article
Oncology
Hisato Kawakami, Yu Sunakawa, Eisuke Inoue, Ryo Matoba, Kenta Noda, Toshiyuki Sato, Chihiro Suminaka, Mami Yamaki, Yasuhiro Sakamoto, Ryohei Kawabata, Atsushi Ishiguro, Yusuke Akamaru, Yosuke Kito, Hiroshi Yabusaki, Jin Matsuyama, Masazumi Takahashi, Akitaka Makiyama, Hidetoshi Hayashi, Kenji Chamoto, Tasuku Honjo, Kazuhiko Nakagawa, Wataru Ichikawa, Masashi Fujii
Summary: The levels of sPD-1, sPD-L1, and sCTLA-4 in the blood plasma of gastric cancer patients before nivolumab treatment are associated with survival. Higher levels of sPD-1, sPD-L1, and sCTLA-4 are correlated with shorter overall survival, while only higher levels of sPD-L1 are associated with shorter progression-free survival. Additionally, sPD-L1 levels are related to the Glasgow prognostic score (GPS) and both sPD-L1 and GPS can independently predict overall survival. Therefore, baseline sPD-L1 levels have the potential to predict survival in advanced gastric cancer patients treated with nivolumab, and the prognostic accuracy can be improved by combining sPD-L1 with GPS.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
T. Yoshino, A. Cervantes, H. Bando, E. Martinelli, E. Oki, R. -H. Xu, N. A. Mulansari, K. Govind Babu, M. A. Lee, C. K. Tan, G. Cornelio, D. Q. Chong, L. -T. Chen, S. Tanasanvimon, N. Prasongsook, K. -H. Yeh, C. Chua, M. D. Sacdalan, W. J. Sow (Jenson), S. T. Kim, R. T. Chacko, R. A. Syaiful, S. Z. Zhang, G. Curigliano, S. Mishima, Y. Nakamura, H. Ebi, Y. Sunakawa, M. Takahashi, E. Baba, S. Peters, C. Ishioka, G. Pentheroudakis
Summary: The ESMO Guidelines for metastatic colorectal cancer (mCRC) were adapted to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for Asian patients. The guidelines were developed by a panel of experts from Asian oncological societies, based on scientific evidence and independent of treatment practices and reimbursement decisions. The aim is to optimize and harmonize the management of mCRC across Asia, considering the differences in screening practices, molecular profiling, and drug approvals and reimbursement strategies.
Review
Oncology
Carsten Bokemeyer, Fortunato Ciardiello, Olivier Dubreuil, Joel Guigay, Stefan Kasper, Per Pfeiffer, Carmine Pinto, Kensei Yamaguchi, Takayuki Yoshino, Christoph Zielinski, Regina Esser, Josep Tabernero
Summary: The every 2 weeks dosing schedule of cetuximab has been approved for use in patients with colorectal cancer and head and neck cancer. Studies have shown similar clinical benefits and side effects compared to the weekly dosing schedule, making it a convenient alternative.
Article
Oncology
Hiroki Yukami, Hisato Kawakami, Toshifumi Yamaguchi, Daisuke Sakai, Toshio Shimokawa, Yukinori Kurokawa, Masahiro Goto, Taroh Satoh
Summary: This study aimed to determine the maximum tolerated dose and recommended dose of the combination of irinotecan, cisplatin, and S-1 in chemotherapy-naive patients with HER2-negative advanced gastric cancer. The results showed that the triplet regimen achieved favorable treatment efficacy in HER2-negative advanced gastric cancer patients and may be a potential option for further treatment.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Multidisciplinary Sciences
Atsushi Ohtsu, Koichi Goto, Takayuki Yoshino
Summary: The SCRUM-Japan platform has played a crucial role in cancer research and treatment through CGP testing and genomically-matched clinical trials. Liquid biopsy has proven to be more advantageous than tissue biopsy in terms of diagnosis and treatment of tumors. Monitoring MRD shows significant effectiveness in predicting cancer recurrence and has the potential to change patient selection for adjuvant therapy.
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES
(2023)
Article
Oncology
Yosuke Kito, Hisato Kawakami, Seiichiro Mitani, Shinichi Nishina, Toshihiko Matsumoto, Takao Tsuzuki, Yudai Shinohara, Hozumi Shimokawa, Ryosuke Kumanishi, Takashi Ohta, Hiroo Katsuya, Takeshi Kawakami, Tomohiro Nishina, Hiroko Hasegawa, Kohei Akiyoshi, Yasutaka Chiba, Kentaro Yamazaki, Shuichi Hironaka, Kei Muro
Summary: The study evaluated the efficacy and safety of trifluridine/tipiracil plus bevacizumab for patients with previously treated metastatic colorectal cancer who were intolerant of intensive therapy.