Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer
Open accessAbstract
BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. The drug may have efficacy in patients with HER2-positive advanced gastric cancer. METHODS: In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer. Patients with centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed while they were receiving at least two previous therapies, including trastuzumab, were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan (6.4 mg per kilogram of body weight every 3 weeks) or physician's choice of chemotherapy. The primary end point was the objective response, according to independent central review. Secondary end points included overall survival, response duration, progression-free survival, confirmed response (response persisting ≥4 weeks), and safety. RESULTS: Of 187 treated patients, 125 received trastuzumab deruxtecan and 62 chemotherapy (55 received irinotecan and 7 paclitaxel). An objective response was reported in 51% of the patients in the trastuzumab deruxtecan group, as compared with 14% of those in the physician's choice group (P<0.001). Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median, 12.5 vs. 8.4 months; hazard ratio for death, 0.59; 95% confidence interval, 0.39 to 0.88; P = 0.01, which crossed the prespecified O'Brien-Fleming boundary [0.0202 on the basis of number of deaths]). The most common adverse events of grade 3 or higher were a decreased neutrophil count (in 51% of the trastuzumab deruxtecan group and 24% of the physician's choice group), anemia (38% and 23%, respectively), and decreased white-cell count (21% and 11%). A total of 12 patients had trastuzumab deruxtecan-related interstitial lung disease or pneumonitis (grade 1 or 2 in 9 patients and grade 3 or 4 in 3), as adjudicated by an independent committee. One drug-related death (due to pneumonia) was noted in the trastuzumab deruxtecan group; no drug-related deaths occurred in the physician's choice group. CONCLUSIONS: Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with HER2-positive gastric cancer. Myelosuppression and interstitial lung disease were the notable toxic effects. (Funded by Daiichi Sankyo; DESTINY-Gastric01 ClinicalTrials.gov number, NCT03329690.).
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ERBB2 and FGFR2 amplifications in stomach cancer are actionable alterations for precision medicine.
“Importantly, KRAS, ERBB2, and FGFR2 amplifications are mutually exclusive in stomach cancer (91), with the latter two types of amplification subtypes already representing actionable alterations for precision medicine approaches (92, 93).”
From Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants (2022) · cites this paper as [92]
Cites
The National Comprehensive Cancer Network
McGivney, W. T. (1998) · Cancer · doi:10.1002/(sici)1097-0142(19980515)82:10+ · Cited by 16,760 · see citing works
Bang, Y.-J., Van Cutsem, E., Feyereislova, A., Chung, H. C., Shen, L., Sawaki, A., Lordick, F., Ohtsu, A., Omuro, Y., Satoh, T., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61121-x · Cited by 7,302 · see citing works
Self-citationGlobal Cancer Incidence and Mortality Rates and Trends—An Update
Torre, L. A., Siegel, R. L., Ward, E., & Jemal, A. (2015) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-15-0578 · Cited by 3,715 · see citing works
Kang, Y., Boku, N., Satoh, T., Ryu, M., Chao, Y., Kato, K., Chung, H. C., Chen, J., Muro, K., Kang, W. K., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31827-5 · Cited by 2,254 · see citing works
Self-citationWilke, H., Muro, K., Cutsem, E. V., Oh, S., Bodoky, G., Shimada, Y., Hironaka, S., Sugimoto, N., Lipatov, O., Kim, T.-Y., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70420-6 · Cited by 2,200 · see citing works
Self-citationPertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer
Swain, S. M., Baselga, J., Kim, S.-B., Ro, J., Semiglazov, V., Campone, M., Ciruelos, E., Ferrero, J.-M., Schneeweiss, A., Heeson, S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1413513 · Cited by 2,164 · see citing works
Trastuzumab deruxtecan in previously treated HER2-positive breast cancer
Modi, S., Saura, C., Yamashita, T., Park, Y. H., Kim, S.-B., Tamura, K., Andre, F., Iwata, H., Ito, Y., Tsurutani, J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1914510 · Cited by 2,006 · see citing works
Fuchs, C. S., Doi, T., Jang, R. W., Muro, K., Satoh, T., Machado, M., Sun, W., Jalal, S. I., Shah, M. A., Metges, J.-P., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.0013 · Cited by 1,784 · see citing works
Self-citationmultifunctional enzymes in cancer
Mohamed, M. M., & Sloane, B. F. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1949 · Cited by 1,267 · see citing works
Ogitani, Y., Aida, T., Hagihara, K., Yamaguchi, J., Ishii, C., Harada, N., Soma, M., Okamoto, H., Oitate, M., Arakawa, S., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2822 · Cited by 1,214 · see citing works
Swain, S. M., Miles, D., Kim, S.-B., Im, Y.-H., Im, S.-A., Semiglazov, V., Ciruelos, E., Schneeweiss, A., Loi, S., Monturus, E., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30863-0 · Cited by 922 · see citing works
A Confidence Interval for the Median Survival Time
Brookmeyer, R., & Crowley, J. (1982) · Biometrics · doi:10.2307/2530286 · Cited by 914 · see citing works
Modi, S., Park, H., Murthy, R. K., Iwata, H., Tamura, K., Tsurutani, J., Moreno‐Aspitia, A., Doi, T., Sagara, Y., Redfern, C. H., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.02318 · Cited by 788 · see citing works
Self-citationOgitani, Y., Hagihara, K., Oitate, M., Naito, H., & Agatsuma, T. (2016) · Cancer Science · doi:10.1111/cas.12966 · Cited by 751 · see citing works
Hecht, J. R., Bang, Y., Qin, S., Chung, H. C., Xu, J., Park, J. O., Jeziorski, K., Shparyk, Y. V., Hoff, P. M., Sobrero, A. F., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.62.6598 · Cited by 624 · see citing works
Self-citationSatoh, T., Xu, R., Chung, H. C., Sun, G., Doi, T., Xu, J., Tsuji, A., Omuro, Y., Li, J., Wang, J., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.6136 · Cited by 622 · see citing works
Self-citationHER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer
Cutsem, E. V., Bang, Y., Feng, F.-Y., Xu, J., Lee, K., Jiao, S., Chong, J. L., López-Sanchez, R. I., Price, T. J., Gladkov, O. A., et al. (2014) · Gastric Cancer · doi:10.1007/s10120-014-0402-y · Cited by 611 · see citing works
Self-citationThuss-Patience, P. C., Shah, M. A., Ohtsu, A., Cutsem, E. V., Ajani, J. A., Castro, H. R., Mansoor, W., Chung, H. C., Bodoky, G., Shitara, K., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30111-0 · Cited by 551 · see citing works
Self-citationShitara, K., Doi, T., Dvorkin, M. V., Mansoor, W., Arkenau, H., Prokharau, A., Alsina, M., Ghidini, M., Faustino, C., Горбунова, В. А., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30739-3 · Cited by 516 · see citing works
Self-citationBang, Y.-J., Ruiz, E. Y., Cutsem, E. V., Lee, K., Wyrwicz, L. S., Schenker, M., Alsina, M., Ryu, M., Chung, H. C., Evesque, L., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy264 · Cited by 501 · see citing works
Self-citationTabernero, J. M., Hoff, P. M., Shen, L., Ohtsu, A., Shah, M. A., Cheng, K., Song, C., Wu, H., Eng‐Wong, J., Kim, K. K., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30481-9 · Cited by 496 · see citing works
Bartley, A. N., Washington, M. K., Colasacco, C., Ventura, C. B., Ismaila, N., Benson, A. B., Carrato, A., Gulley, M. L., Jain, D., Kakar, S., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.69.4836 · Cited by 465 · see citing works
Cathepsin B: Multiple roles in cancer
Aggarwal, N., & Sloane, B. F. (2014) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201300105 · Cited by 404 · see citing works
Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer
Janjigian, Y. Y., Sánchez-Vega, F., Jonsson, P., Chatila, W. K., Hechtman, J. F., Ku, G. Y., Riches, J. C., Tuvy, Y., Kundra, R., Bouvier, N., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0787 · Cited by 374 · see citing works
Muro, K., Lordick, F., Tsushima, T., Pentheroudakis, G. E., Baba, E., Lu, Z., Cho, B. C., Nor, I. M., NG, M. M., Chen, L. T., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy498 · Cited by 290 · see citing works
Self-citationGrabsch, H. I., Sivakumar, S., Gray, S., et al. (2010) · Analytical Cellular Pathology · doi:10.1155/2010/519498 · Cited by 264 · see citing works
Shitara, K., Iwata, H., Takahashi, S., Tamura, K., Park, H., Modi, S., Tsurutani, J., Kadowaki, S., Yamaguchi, K., Iwasa, S., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30088-9 · Cited by 232 · see citing works
Self-citationMuro, K., Cutsem, E. V., Narita, Y., Pentheroudakis, G. E., Baba, E., Li, J., Ryu, M. H., Zamaniah, W. I. W., Yong, W. P., Yeh, K. H., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy502 · Cited by 216 · see citing works
Self-citationMakiyama, A., Sukawa, Y., Kashiwada, T., Kawada, J., Hosokawa, A., Horie, Y., Tsuji, A., Moriwaki, T., Tanioka, H., Shinozaki, K., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.03077 · Cited by 204 · see citing works
Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer
Wang, D., Liu, Z., Lu, Y., Bao, H., Wu, X., Zeng, Z.-L., Liu, Z., Zhao, Q., He, C.-Y., Lu, J., et al. (2018) · Gut · doi:10.1136/gutjnl-2018-316522 · Cited by 196 · see citing works
Pietrantonio, F., Caporale, M., Morano, F., Scartozzi, M., Gloghini, A., Vita, F. D., Giommoni, E., Fornaro, L., Aprile, G., Melisi, D., et al. (2016) · International Journal of Cancer · doi:10.1002/ijc.30408 · Cited by 157 · see citing works
HER2 heterogeneity in gastric/gastroesophageal cancers: From benchside to practice
Grillo, F., Fassan, M., Sarocchi, F., Fiocca, R., & Mastracci, L. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i26.5879 · Cited by 147 · see citing works
Marcoux, J., Champion, T., Colas, O., Wagner‐Rousset, E., Corvaı̈a, N., DORSSELAER, A. V., Beck, A., & Cianférani, S. (2015) · Protein Science · doi:10.1002/pro.2666 · Cited by 143 · see citing works
Pulmonary toxicity from novel antineoplastic agents
Dimopoulou, I., Bamias, A., Lyberopoulos, P., & Dimopoulos, M. A. (2005) · Annals of Oncology · doi:10.1093/annonc/mdj057 · Cited by 142 · see citing works
Grabsch, H. I., Sivakumar, S., Gray, S., et al. (2010) · PubMed · doi:10.3233/clo-2009-0497 · Cited by 139 · see citing works
Nagai, Y., Oitate, M., Shiozawa, H., & Ando, O. (2018) · Xenobiotica · doi:10.1080/00498254.2018.1531158 · Cited by 108 · see citing works
Krop, I. E., Suter, T. M., Dang, C. T., Dirix, L. Y., Romieu, G., Zamagni, C., Citron, M. L., Campone, M., Xu, N., Smitt, M. C., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.58.7782 · Cited by 93 · see citing works
Takegawa, N., Tsurutani, J., Kawakami, H., Yonesaka, K., Kato, R., Haratani, K., Hayashi, H., Takeda, M., Nonagase, Y., Maenishi, O., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32408 · Cited by 90 · see citing works
Self-citationPrognostic Impact of Cysteine Proteases Cathepsin B and Cathepsin L in Pancreatic Adenocarcinoma
Niedergethmann, M., Wostbrock, B., Sturm, J. W., et al. (2004) · Pancreas · doi:10.1097/00006676-200410000-00005 · Cited by 84 · see citing works
Shiose, Y., Ochi, Y., Kuga, H., Yamashita, F., & Hashida, M. (2007) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.30.2365 · Cited by 56 · see citing works
Wide application of a novel topoisomerase I inhibitor-based drug conjugation technology
Ogitani, Y., Abe, Y., Iguchi, T., Yamaguchi, J., Terauchi, T., Kitamura, M., Goto, K., Goto, M., Oitate, M., Yukinaga, H., et al. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.08.082 · Cited by 53 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants
Hofmann, M. H., Gerlach, D., Misale, S., Petronczki, M., & Kraut, N. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1331 · Cited by 336 · see citing works
Optimizing the safety of antibody–drug conjugates for patients with solid tumours
Tarantino, P., Ricciuti, B., Pradhan, S. M., & Tolaney, S. M. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00783-w · Cited by 269 · see citing works
The Journey of Antibody–Drug Conjugates: Lessons Learned from 40 Years of Development
Colombo, R., Tarantino, P., Rich, J. R., LoRusso, P. M., & de Vries, E. G. E. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0708 · Cited by 254 · see citing works
Yoshino, T., Di Bartolomeo, M., Raghav, K., Masuishi, T., Loupakis, F., Kawakami, H., Yamaguchi, K., Nishina, T., Wainberg, Z., Elez, E., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38032-4 · Cited by 178 · see citing works
Self-citationHingorani, P., Zhang, W., Zhang, Z., Xu, Z., Wang, W.-L., Roth, M. E., Wang, Y., Gill, J. B., Harrison, D. J., Teicher, B. A., et al. (2022) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-21-0758 · Cited by 28 · see citing works
Babkoff, A., Zick, A., Hubert, A., Tarantino, P., & Grinshpun, A. (2024) · ESMO Gastrointestinal Oncology · doi:10.1016/j.esmogo.2023.100032 · Cited by 14 · see citing works
Resistance to Anti-HER2 Therapies in Gastrointestinal Malignancies
Mo, C., Sterpi, M., Jeon, H., & Bteich, F. (2024) · Cancers · doi:10.3390/cancers16162854 · Cited by 8 · see citing works
- Authors
- Shitara, K., Bang, Y.-J., Iwasa, S., Sugimoto, N., Ryu, M.-H., Sakai, D., Chung, H.-C., Kawakami, H., Yabusaki, H., Lee, J., Saito, K., Kawaguchi, Y., Kamio, T., Kojima, A., Sugihara, M., & Yamaguchi, K.
- Affiliations
- Seoul National University (KR)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-06-18
- Volume
- 382
- Issue
- 25
- Pages
- 2419-2430
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3147820834
- Cited by
- 1,333
- References
- 41
- Citations by year
- 2026: 177 · 2025: 247 · 2024: 235 · 2023: 264 · 2022: 213 · 2021: 167 · 2020: 27 · 2018: 1
- FWCI
- 94.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Daiichi Sankyo Company
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- trastuzumab deruxtecan, HER2-positive gastric cancer, gastroesophageal junction adenocarcinoma, antibody-drug conjugates, topoisomerase I inhibitor, chemotherapy comparison, objective response rate, overall survival, neutropenia, interstitial lung disease, treatment safety, irinotecan
- MeSH terms
- Trastuzumab, Irinotecan, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Bone Marrow, Camptothecin, Esophageal Neoplasms, Female, Humans, Male, Middle Aged, Stomach Neoplasms, Survival Analysis, Paclitaxel, Lung Diseases, Interstitial, Erb-b2 Receptor Tyrosine Kinases, Immunoconjugates, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
