TY - JOUR
T1 - Antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-low–expressing advanced breast cancer
T2 - Results from a phase Ib study
AU - Modi, Shanu
AU - Park, Haeseong
AU - Murthy, Rashmi K.
AU - Iwata, Hiroji
AU - Tamura, Kenji
AU - Tsurutani, Junji
AU - Moreno-Aspitia, Alvaro
AU - Doi, Toshihiko
AU - Sagara, Yasuaki
AU - Redfern, Charles
AU - Krop, Ian E.
AU - Lee, Caleb
AU - Fujisaki, Yoshihiko
AU - Sugihara, Masahiro
AU - Zhang, Lin
AU - Shahidi, Javad
AU - Takahashi, Shunji
N1 - Funding Information:
We thank the patients who participated in this study and their families and caregivers. We also thank the staff and investigators at all study sites. Medical writing and editorial support was provided by Nicole Seneca, PhD, and Stefan Kolata, PhD, of AlphaBioCom, and funded by Daiichi Sankyo.
Publisher Copyright:
© 2020 by American Society of Clinical Oncology.
PY - 2020
Y1 - 2020
N2 - PURPOSE Trastuzumab deruxtecan (T-DXd, formerly DS-8201a) is a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload. A dose escalation and expansion phase I study evaluated the safety and activity of T-DXd in patients with advanced HER2-expressing/mutated solid tumors. Here, results for T-DXd at the recommended doses for expansion (RDE) in patients with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization2) breast cancer (ClinicalTrials.gov identifier: NCT02564900) are reported. PATIENTS AND METHODS Eligible patients had advanced/metastatic HER2-low–expressing breast cancer refractory to standard therapies. The RDE of 5.4 or 6.4 mg/kg T-DXd were administered intravenously once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. Antitumor activity and safety were assessed. RESULTS Between August 2016 and August 2018, 54 patients were enrolled and received $ 1 dose of T-DXd at the RDE. Patients were extensively pretreated (median, 7.5 prior therapies). The confirmed objective response rate by independent central review was 20/54 (37.0%; 95% CI, 24.3% to 51.3%) with median duration of response of 10.4 months (95% CI, 8.8 month to not evaluable). Most patients (53/54; 98.1%) experienced $ 1 treatment-emergent adverse event (TEAE; grade $ 3; 34/54; 63.0%). Common ($ 5%) grade $ 3 TEAEs included decreases in neutrophil, platelet, and WBC counts; anemia; hypokalemia; AST increase; decreased appetite; and diarrhea. Three patients treated at 6.4 mg/kg suffered fatal events associated with T-DXd–induced interstitial lung disease (ILD)/pneumonitis as determined by an independent adjudication committee. CONCLUSION The novel HER2-targeted ADC, T-DXd, demonstrated promising preliminary antitumor activity in patients with HER2-low breast cancer. Most toxicities were GI or hematologic in nature. ILD is an important identified risk and should be monitored closely and proactively managed.
AB - PURPOSE Trastuzumab deruxtecan (T-DXd, formerly DS-8201a) is a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload. A dose escalation and expansion phase I study evaluated the safety and activity of T-DXd in patients with advanced HER2-expressing/mutated solid tumors. Here, results for T-DXd at the recommended doses for expansion (RDE) in patients with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization2) breast cancer (ClinicalTrials.gov identifier: NCT02564900) are reported. PATIENTS AND METHODS Eligible patients had advanced/metastatic HER2-low–expressing breast cancer refractory to standard therapies. The RDE of 5.4 or 6.4 mg/kg T-DXd were administered intravenously once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. Antitumor activity and safety were assessed. RESULTS Between August 2016 and August 2018, 54 patients were enrolled and received $ 1 dose of T-DXd at the RDE. Patients were extensively pretreated (median, 7.5 prior therapies). The confirmed objective response rate by independent central review was 20/54 (37.0%; 95% CI, 24.3% to 51.3%) with median duration of response of 10.4 months (95% CI, 8.8 month to not evaluable). Most patients (53/54; 98.1%) experienced $ 1 treatment-emergent adverse event (TEAE; grade $ 3; 34/54; 63.0%). Common ($ 5%) grade $ 3 TEAEs included decreases in neutrophil, platelet, and WBC counts; anemia; hypokalemia; AST increase; decreased appetite; and diarrhea. Three patients treated at 6.4 mg/kg suffered fatal events associated with T-DXd–induced interstitial lung disease (ILD)/pneumonitis as determined by an independent adjudication committee. CONCLUSION The novel HER2-targeted ADC, T-DXd, demonstrated promising preliminary antitumor activity in patients with HER2-low breast cancer. Most toxicities were GI or hematologic in nature. ILD is an important identified risk and should be monitored closely and proactively managed.
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U2 - 10.1200/JCO.19.02318
DO - 10.1200/JCO.19.02318
M3 - Article
C2 - 32058843
AN - SCOPUS:85081268424
SN - 0732-183X
VL - 38
SP - 1887
EP - 1896
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 17
ER -