dslogo
azlogo

DESTINY-Breast03: Brain Metastases Subgroup Analysis (May 21, 2021 DCO Date) 

Key Inclusion Criteria

Key Inclusion Criteria1-31. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.2. Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154.3. Daiichi Sankyo, Inc. DS-8201a versus T-DM1 for human epidermal growth factor receptor 2 (HER2)-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane [DESTINY-Breast03]. ClinicalTrials.gov website. Available at https://clinicaltrials.gov/ct2/show/NCT03529110

Patients were included if:

  • They had brain metastases that were treated, asymptomatic, and did not require corticosteroids or anticonvulsants to control symptoms
    • At baseline,16.5% of patients in the T-DXd treatment arm had brain metastases versus 14.8% of patients in the T-DM1 treatment arm11. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.
  • A minimum of 2 weeks had elapsed between the end of whole brain radiotherapy and study enrollment1-31. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.2. Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154.3. Daiichi Sankyo, Inc. DS-8201a versus T-DM1 for human epidermal growth factor receptor 2 (HER2)-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane [DESTINY-Breast03]. ClinicalTrials.gov website. Available at https://clinicaltrials.gov/ct2/show/NCT03529110
  • Brain imaging was performed by CT or MRI for patients with brain metastases

Results

Results11. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.

Confirmed ORR and Best Overall Response 

Confirmed ORR and Best Overall Response11. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.

Confirmed ORR and Best Overall Response.11. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.

T-DXdT-DM1

Overall Population

(n=261)a

Patients With BMs

(n=43)

Patients Without BMs

(n=218)

Overall Population

(n=263)a

Patients With BMs

(n=39)

Patients Without BMs

(n=224)

Confirmed ORR, n (%)b 

[95% CI]

208 (79.7)

[74.3-84.4]

29 (67.4)

[51.5-80.9]

179 (82.1)

[76.4-87.0]

90 (34.2)

[28.5-40.3]

8 (20.5)

[9.3-36.5]

82 (36.6)

[30.3-43.3]

CR42 (16.1)  2 (4.7) 40 (18.3)23 (8.7)  0 23 (10.3)
PR166 (63.6) 27 (62.8)139 (63.8)67 (25.5)  8 (20.5) 59 (26.3)
SD44 (16.9) 11 (25.6) 33 (15.1)112 (42.6) 22 (56.4) 90 (40.2)
PD3 (1.1)  1 (2.3)  2 (0.9)46 (17.5)  7 (17.9) 39 (17.4)
NE6 (2.3)  2 (4.7)  4 (1.8)15 (5.7)  2 (5.1) 13 (5.8)
CR + PR + SD (DCR)252 (96.6)40 (93.0)212 (97.2)202 (76.8)30 (76.9)172 (76.8)

mDOR

[95% CI], mo

NE

[20.3-NE]

12.9

[8.5-NE]

NE

[20.3-NE]

NE

[12.6-NE]

7.2

[2.8-NE]

NE

[12.6-NE]

aOnly subjects with measurable disease at baseline and at least 1 postbaseline target lesion assessment are included; bBased on BICR.

Intracranial Response

Intracranial Response11. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.

Intracranial Response per BICR Using RECIST v1.111. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.

Intracranial Response per BICR Using RECIST v1.111. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.

<p>Intracranial Response per BICR Using RECIST v1.1<span class="tooltip"><span class="tooltip-text"><sup>1</sup></span><span class="tooltip-content" style="display: none;"><span>1. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. <em>Cancer Res</em>. 2022;82(suppl 4). Abs GS3-01.</span></span></span></p>

Note: Table includes target and non-target lesions. Only patients with target lesion assessments are eligible for inclusion in waterfall. Red line at 20% indicates progressive disease; black line at -30% indicates partial response.

aDenominator for percentages is the number of subjects in the full analysis set with brain metastases tumor assessment.

Abbreviations

BICR = blinded independent central review

;

BM = brain metastases

;

CR = complete response

;

CT = computed tomography

;

DCO = data cutoff

;

DCR = disease control rate

;

HR = hazard ratio

;

KM = Kaplan-Meier

;

NE = not evaluable

;

mDOR = median duration of response

;

mPFS = median progression-free survival

;

mo = months

;

MRI = magnetic resonance imaging

;

ORR = objective response rate

;

PD = progressive disease

;

PR = partial response

;

RECIST = Response Evaluation Criteria in Solid Tumors

;

SD = stable disease

;

T-DM1 = trastuzumab emtansine

;

T-DXd = trastuzumab deruxtecan

References

1. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.

2. Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154.

3. Daiichi Sankyo, Inc. DS-8201a versus T-DM1 for human epidermal growth factor receptor 2 (HER2)-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane [DESTINY-Breast03]. ClinicalTrials.gov website. Available at https://clinicaltrials.gov/ct2/show/NCT03529110

Please note that this content may contain some data and/or patient populations which are considered off-label in your country. Providing this information does not constitute any recommendation for use. AstraZeneca is providing this material as an information service and professional courtesy. 

To help us improve our content for health care professionals, please take this short survey.

Feedback Survey

©2023 AstraZeneca. All rights reserved.