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DESTINY-Breast03: Study Design

Study Design

Study of T-DXd in Patients With Unresectable/Metastatic BC Previously Treated With Trastuzumab and a Taxane11. 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.

  • DESTINY-Breast03 is an open-label, multicenter, Phase III study of T-DXd vs T‑DM1 in patients with HER2-positive, unresectable/metastatic BC who were previously treated with trastuzumab and a taxane.11. 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.
  • A total of 524 patients with HER2 positive BC were randomly assigned 1:1 to receive T-DXd 5.4 mg/kg (n=261) or T-DM1 3.6 mg/kg (n=263) IV Q3W.11. 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.

Study Design1-41. Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154.2. Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [presentation and abstract]. Presented at: European Society for Medical Oncology (ESMO) Breast Cancer 2022; May 3-5, 2022. Ann Oncol. 2022;33(suppl 3). Abs 1630.3. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial [article]. The Lancet. 2022;401(10371):105-117.4. Cortés J, Im SA, Iwata H, et al. Subgroup analysis by disease history and prior treatments of patients with HER2-positive metastatic breast cancer from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan vs trastuzumab emtansine [poster and abstract]. Poster presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2022; September 9-13, 2022. Ann Oncol. 2022;33(suppl 7). Abs 236P.

Study Design1-41. Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154.2. Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [presentation and abstract]. Presented at: European Society for Medical Oncology (ESMO) Breast Cancer 2022; May 3-5, 2022. Ann Oncol. 2022;33(suppl 3). Abs 1630.3. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial [article]. The Lancet. 2022;401(10371):105-117.4. Cortés J, Im SA, Iwata H, et al. Subgroup analysis by disease history and prior treatments of patients with HER2-positive metastatic breast cancer from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan vs trastuzumab emtansine [poster and abstract]. Poster presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2022; September 9-13, 2022. Ann Oncol. 2022;33(suppl 7). Abs 236P.

<p>Study Design<span class="tooltip"><span class="tooltip-text"><sup>1-4</sup></span><span class="tooltip-content" style="display: none;"><span>1. Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. <em>N Engl J Med. </em>2022;386:1143-1154.</span><span>2. <span style="background-color: rgb(252, 252, 252);">Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [presentation and abstract]. Presented at: European Society for Medical Oncology (ESMO) Breast Cancer 2022; May 3-5, 2022. </span><em style="background-color: rgb(252, 252, 252);">Ann Oncol</em><span style="background-color: rgb(252, 252, 252);">. 2022;33(suppl 3). Abs 1630.</span></span><span>3. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial [article]. <em>The Lancet</em>. 2022;401(10371):105-117.</span><span>4. Cortés J, Im SA, Iwata H, et al. Subgroup analysis by disease history and prior treatments of patients with HER2-positive metastatic breast cancer from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan vs trastuzumab emtansine [poster and abstract]. Poster presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2022; September 9-13, 2022. <em>Ann Oncol</em>. 2022;33(suppl 7). Abs 236P.</span></span></span></p>

aHER2 IHC 3+ or IHC 2+/ISH+ based on central confirmation; bProgression during or <6 months after completing neoadjuvant or adjuvant therapy involving trastuzumab or a taxane; cBefore protocol amendment, patients with stable, untreated BM were eligible; d4 patients were randomly assigned but not treated; e2 patients were randomly assigned but not treated; f80% powered at 2-sided significance level of 5%; gIn patients with exactly 1 prior line of therapy in the metastatic setting, excluding hormone therapy.

Key Eligibility Criteria

Key Eligibility Criteria3,5,63. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial [article]. The Lancet. 2022;401(10371):105-117.5. 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/NCT035291106. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results of the randomized, phase 3 study DESTINY-Breast03 [presentation and supplementary material]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2022 Annual Meeting; December 6-10, 2022.

Key Eligibility Criteria in DESTINY-Breast033,5,63. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial [article]. The Lancet. 2022;401(10371):105-117.5. 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/NCT035291106. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results of the randomized, phase 3 study DESTINY-Breast03 [presentation and supplementary material]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2022 Annual Meeting; December 6-10, 2022.
Key Inclusion CriteriaKey Exclusion Criteria

Age ≥18 years (subject to local regulatory requirements)

Previous treatment with anti-HER2 ADC in metastatic setting or in adjuvant/neo-adjuvant setting with disease progression after ≤12 months

Pathologically documented breast cancer that is unresectable or metastatic, has HER2-positive expression confirmed per protocol, and was previously treated with trastuzumab and taxane in the advanced/metastatic settinga

Uncontrolled or significant cardiovascular disease

Documented radiologic progression of disease

Medical history of (non-infectious) ILD/pneumonitis that required steroids or active or suspected ILD/pneumonitis

Protocol-defined adequate renal and hepatic function

Spinal cord compression or active CNS metastases that are untreated and symptomatic, or require therapy with corticosteroids or anticonvulsants to control symptoms

aProgression during or <6 months after completing adjuvant therapy involving trastuzumab or taxane..

Abbreviations

ADC = antibody-drug conjugate

;

BC = breast cancer

;

BICR = blind independent central review

;

BM = brain metastases

;

CT = computed tomography

;

DoR = duration of response

;

HEOR = health economic outcomes research

;

HER2 = human epidermal growth factor receptor 2

;

IHC = immunohistochemistry

;

ILD = interstitial lung disease

;

ISH = in situ hybridization

;

IV = intravenous

;

MRI = magnetic resonance imaging

;

ORR = objective response rate

;

OS = overall survival

;

PFS = progression-free survival

;

PRO = patient reported outcomes

;

Q3W = every 3 weeks

;

R = randomization

;

T-DXd = trastuzumab deruxtecan

;

T-DM1 = trastuzumab emtansine

References

1. 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.

2. Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [presentation and abstract]. Presented at: European Society for Medical Oncology (ESMO) Breast Cancer 2022; May 3-5, 2022. Ann Oncol. 2022;33(suppl 3). Abs 1630.

3. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial [article]. The Lancet. 2022;401(10371):105-117.

4. Cortés J, Im SA, Iwata H, et al. Subgroup analysis by disease history and prior treatments of patients with HER2-positive metastatic breast cancer from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan vs trastuzumab emtansine [poster and abstract]. Poster presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2022; September 9-13, 2022. Ann Oncol. 2022;33(suppl 7). Abs 236P.

5. 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

6. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results of the randomized, phase 3 study DESTINY-Breast03 [presentation and supplementary material]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2022 Annual Meeting; December 6-10, 2022.

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Document ID: 8db67364-6c52-4ea0-b987-9d4900884ec2
Last updated: 27-June-2024

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