Destiny Breast 11 Trial - Clarification
I believe you are asking about the DESTINY-Breast trials, which evaluate trastuzumab deruxtecan (T-DXd), not "Destiny Breast 11" specifically. The most relevant trials in this series are DESTINY-Breast01, 03, and 05.
DESTINY-Breast03: The Most Relevant Trial for HER2+ Metastatic Disease
DESTINY-Breast03 demonstrated superior efficacy of trastuzumab deruxtecan over T-DM1 in previously treated HER2-positive metastatic breast cancer, establishing T-DXd as a preferred option in this setting 1.
Relevance to Your Patient Scenario (pCR After Neoadjuvant Therapy)
For your patient who achieved pCR after neoadjuvant chemotherapy with trastuzumab-pertuzumab, the DESTINY trials are NOT directly applicable to current management decisions 1, 2.
Current Standard Management for pCR Patients
- Continue trastuzumab plus pertuzumab to complete 1 year total duration (18 cycles including neoadjuvant period) 2.
- This recommendation is based on the excellent prognosis associated with pCR and the established benefit of completing dual HER2 blockade 2.
- For high-risk patients (≥2 cm tumors and/or node-positive at diagnosis), completing the full year of dual blockade is particularly important despite achieving pCR 2.
Where DESTINY Trials Become Relevant
DESTINY-Breast05 (NCT04622319) is the trial that matters for early breast cancer patients 1.
- This ongoing trial compares trastuzumab deruxtecan versus T-DM1 in patients with residual invasive disease after neoadjuvant therapy 1.
- This trial does NOT apply to your patient who achieved pCR 1.
Clinical Algorithm for Post-Neoadjuvant HER2+ Breast Cancer
If pCR Achieved (Your Patient's Scenario):
- Continue trastuzumab-pertuzumab to complete 1 year total 2.
- No role for T-DM1 or trastuzumab deruxtecan 1, 2.
- Cardiac monitoring with LVEF assessment remains mandatory 2, 3.
If Residual Disease Present:
- Switch to T-DM1 for 14 cycles (KATHERINE trial standard) 1, 4.
- T-DM1 reduces recurrence risk by 50% compared to continuing trastuzumab (HR 0.50,95% CI 0.39-0.64, p<0.001) 4.
- DESTINY-Breast05 results may change this paradigm in the future if trastuzumab deruxtecan proves superior to T-DM1 1.
Important Caveats
- Do not confuse metastatic disease trials (DESTINY-Breast01, 03) with early breast cancer management 1.
- Trastuzumab deruxtecan is currently FDA-approved for metastatic disease after prior anti-HER2 therapy, not for the adjuvant/post-neoadjuvant setting 1.
- The only scenario where DESTINY trials inform early breast cancer treatment is through the ongoing DESTINY-Breast05 trial for patients with residual disease 1.
Summary of DESTINY Trial Series
- DESTINY-Breast01: Established T-DXd efficacy in heavily pretreated metastatic HER2+ breast cancer 1.
- DESTINY-Breast03: Showed T-DXd superiority over T-DM1 in metastatic setting 1.
- DESTINY-Breast05: Ongoing trial comparing T-DXd versus T-DM1 in early breast cancer with residual disease post-neoadjuvant therapy 1.
For your specific patient with pCR, stick with the proven strategy: complete 1 year of trastuzumab-pertuzumab dual blockade 2.