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Overall Safety Summary

Overall Safety Summary1,21.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [supplementary appendix]. N Engl J Med. 2022;387:9-20.2.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) Vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: results of DESTINY-Breast04, a randomized, phase 3 study [abstract and presentation]. Presented at: American Society of Clinical Oncology (ASCO) Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 17). Abs LBA3.

  • The median treatment duration was 8.2 months (range, 0.2-33.3) for T‑DXd and 3.5 months (range, 0.3-17.6) for TPC.33.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [article]. N Engl J Med. 2022;387:9-20
  • The most common TEAE associated with treatment discontinuation was pneumonitis (8.2%) for T-DXd and peripheral sensory neuropathy (2.3%) for TPC.22.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) Vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: results of DESTINY-Breast04, a randomized, phase 3 study [abstract and presentation]. Presented at: American Society of Clinical Oncology (ASCO) Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 17). Abs LBA3.
  • The most common TEAE associated with dose reduction for T-DXd was nausea (4.6%) for T-DXd and neutropenia (14.0%) for TPC.22.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) Vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: results of DESTINY-Breast04, a randomized, phase 3 study [abstract and presentation]. Presented at: American Society of Clinical Oncology (ASCO) Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 17). Abs LBA3.


Overall Safety Summary.2,32.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) Vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: results of DESTINY-Breast04, a randomized, phase 3 study [abstract and presentation]. Presented at: American Society of Clinical Oncology (ASCO) Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 17). Abs LBA3.3.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [article]. N Engl J Med. 2022;387:9-20


Safety Analysis Set4.  

Type of Adverse Events, n (%)

T-DXd

(n=371)

TPC

(n=172)

TEAEs

  • Grade ≥3

369 (99.5)

195 (52.6)

169 (98.3)

116 (67.4)

Serious TEAEs103 (27.8)43 (25.0)

TEAEs associated with dose discontinuations

  • Drug-related

60 (16.2)

56 (15.1)

14 (8.1)

12 (7.0)

TEAEs associated with dose interruptions

  • Drug-related

143 (38.5)

106 (28.6)

72 (41.9)

62 (36.0)

TEAEs associated with dose reductions

  • Drug-related

84 (22.6)

77 (20.8)

66 (38.4)

64 (37.2)

TEAEs associated with deaths

  • Drug-related

14 (3.8)

7 (1.9)

5 (2.9)

0

1Safety analyses were performed in patients who received ≥1 dose of a study regimen.

Exposure-Adjusted Incidence Rates

Exposure-Adjusted Incidence Rates11.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [supplementary appendix]. N Engl J Med. 2022;387:9-20.

EAIR of TEAEs.11.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [supplementary appendix]. N Engl J Med. 2022;387:9-20.


Safety Analysis Set a

Type of Adverse Events

T-DXd

(n=371)

TPC

(n=172)

Total Patient-Years of Exposure, yearsa283.5563.59

Any TEAEs, n (%)

  • EAIR per patient-year

369 (99.5)

1.30

169 (98.3)

2.66

Grade ≥3 TEAEs, n (%)

  • EAIR per patient-year

195 (52.6)

0.69

116 (67.4)

1.82

Serious TEAEs, n (%)

  • EAIR per patient-year

103 (27.8)

0.36

43 (25.0)

0.68

TEAEs associated with dose discontinuations, n (%)

  • EAIR per patient-year

60 (16.2)

0.21

14 (8.1)

0.22

TEAEs associated with dose interruptions, n (%)

  • EAIR per patient-year

143 (38.5)

0.50

72 (41.9)

1.13

TEAEs associated with dose reductions, n (%)

  • EAIR per patient-year

84 (22.6)

0.30

66 (38.4)

1.04

TEAEs associated with deaths, n (%)

  • EAIR per patient-year

14 (3.8)

0.05

5 (2.9)

0.08

aPatient-years of exposure are the treatment duration with year as unit.

Drug-Related TEAEs in ≥20% of Patients

Drug-Related TEAEs in ≥20% of Patients33.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [article]. N Engl J Med. 2022;387:9-20

Drug-Related TEAEs in ≥20% of Patients.33.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [article]. N Engl J Med. 2022;387:9-20
System Organ Class
Preferred term, n (%)

T-DXd

(n=371)

TPC

(n=172)

All GradesGrade ≥3All GradesGrade ≥3
Gastrointestinal disorders    
Nausea271 (73.0)17 (4.6)41 (23.8)0
Vomiting126 (34.0)5 (1.3)17 (9.9)0
Diarrhea83 (22.4)4 (1.1)31 (18.0)3 (1.7)
Constipation79 (21.3)022 (12.8)0
Blood and lymphatic system disorders    
Neutropenia10.  123 (33.2)51 (13.7)88 (51.2)70 (40.7)
Anemia10.  123 (33.2)30 (8.1)39 (22.7)8 (4.7)
Thrombocytopenia10.  88 (23.7)19 (5.1)16 (9.3)1 (0.6)
Leukopenia10.  86 (23.2)24 (6.5)54 (31.4)33 (19.2)
Investigations    
Transaminase increased10.  87 (23.5)12 (3.2)39 (22.7)14 (8.1)
General disorders    
Fatigue10.  177 (47.7)28 (7.5)    73 (42.4)8 (4.7)
Metabolism and nutrition disorders    
Decreased appetite106 (28.6)9 (2.4)28 (16.3)2 (1.2)
Skin and subcutaneous tissue disorders    
Alopecia140 (37.7)056 (32.6)0

Note: Shown are adverse events that emerged or worsened after initiation of a trial drug until 47 days after the last dose of the trial drug and that were adjudicated as being related to a trial drug by an independent committee 


2This category includes the preferred terms neutrophil count decreased and neutropenia; 3This category includes the preferred terms hemoglobin decreased, red-cell count decreased, anemia, and hematocrit decreased; 4This category includes the preferred terms platelet count decreased and thrombocytopenia; 5This category includes the preferred terms white-cell count decreased and leukopenia; 6This category includes the preferred terms transaminases increased, aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyltransferase increased, liver function test abnormal, hepatic function abnormal; 7This category includes the preferred terms fatigue, asthenia, and malaise.

Adverse Events of Special Interest

Adverse Events of Special Interest2,32.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) Vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: results of DESTINY-Breast04, a randomized, phase 3 study [abstract and presentation]. Presented at: American Society of Clinical Oncology (ASCO) Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 17). Abs LBA3.3.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [article]. N Engl J Med. 2022;387:9-20

Summary of Adverse Events of Special Interest.2,32.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) Vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: results of DESTINY-Breast04, a randomized, phase 3 study [abstract and presentation]. Presented at: American Society of Clinical Oncology (ASCO) Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 17). Abs LBA3.3.Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [article]. N Engl J Med. 2022;387:9-20
n (%)Grade 1Grade 2Grade 3Grade 4Grade 5Any Grade
Adjudicated as drug-related ILD/pneumonitis

T-DXd (n=371)

TPC (n=172)

13 (3.5)

1 (0.6)

24 (6.5)

0

5 (1.3)

0

0

0

3 (0.8)13.  

0

45 (12.1)

1 (0.6)

Ejection fraction decrease, n (%)13.  

T-DXd (n=371)

TPC (n=172)

1 (0.3)

0

14 (3.8)

0

1 (0.3)

0

0

0

0

0

16 (4.3)

0

Cardiac failure13.  

T-DXd (n=371)

TPC (n=172)

0

0

1 (0.3)

0

1 (0.3)

0

0

0

0

0

2 (0.5)

0

1Median time to onset of ILD/pneumonitis for patients with T-DXd was 129.0 days (range, 26-710); 2Left ventricular dysfunction was reported in a total of 17 (4.6%) patients in the T-DXd arm. One patient initially experienced ejection fraction decrease, then later developed cardiac failure; 3Both patients with cardiac failure were reported to have recovered.

Abbreviations

DCO = data cut-off

;

EAIR = exposure-adjusted incidence rate

;

ILD = interstitial lung disease

;

T-DXd = trastuzumab deruxtecan

;

TEAE = treatment emergent adverse event

;

TPC = treatment of physician's choice

References

1. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [supplementary appendix]. N Engl J Med. 2022;387:9-20.
2. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) Vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: results of DESTINY-Breast04, a randomized, phase 3 study [abstract and presentation]. Presented at: American Society of Clinical Oncology (ASCO) Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 17). Abs LBA3.
3. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer [article]. N Engl J Med. 2022;387:9-20

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