- Results from the multicenter, open-label, randomized phase 3 DESTINY Breast11 trial show that neoadjuvant antibody-drug conjugate trastuzumab deruxtecan improved pathological complete response in patients with high-risk HER2+ early breast cancer compared to standard treatment with chemotherapy.
- Achieving a complete pathological response is associated with a significant reduction in the risk of recurrence, underscoring the need to develop new treatment strategies that enhance efficacy without increasing toxicity to preserve the quality of life of patients.
- Co-authored by Santiago Escrivá de Romaní, Medical Oncologist at the Vall d’Hebron University Hospital and Investigator of VHIO’s Breast Cancer Group, findings from DESTINY Breast11 were presented at today’s Presidential Session of the 2025 European Society for Medical Oncology (ESMO) Annual Congress, 17-21 October, Berlin.
Results from the international phase 3 DESTINY-Breast11 study show that neoadjuvant therapy with antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) followed by the standard neoadjuvant triplet of dual HER2 blockade with trastuzumab and pertuzumab combined with paclitaxel chemotherapy, demonstrated a clinically meaningful and statistically significant improvement in pathological complete response (pCR) versus standard of care in patients with high-risk, locally advanced HER2+ breast cancer.
The findings, co-authored by Santiago Escrivá de Romaní, Medical Oncologist at the Vall d’Hebron University Hospital and Investigator of VHIO’s Breast Cancer Group, were presented today at a Presidential Session* of the 2025 European Society for Medical Oncology (ESMO) Annual Congress, 17-21 October, Berlin, by Nadia Harbeck, Director of the Breast Center, LMU University Hospital, Munich, Germany.
“One in three patients diagnosed with early-stage breast cancer are considered to have a higher risk of recurrence and a poor prognosis if they do not receive optimal treatment. Therefore, achieving a complete pathological response, namely, the absence of cancer cells in the breast and lymph nodes at surgery after neoadjuvant treatment, is key to reducing the risk of relapse,” said Santiago Escrivá de Romaní.
Combination chemotherapy regimens, often including anthracyclines, are the current standard for neoadjuvant treatment for many breast cancers Anthracyclines are a family of chemotherapy drugs used to treat many types of cancer, but they can cause poorly tolerated secondary side effects that, in rare cases, can be associated with long-term treatment-related cardiovascular toxicity.
“Recent research advances in HER2-positive breast cancer have led the development of targeted therapy drugs countering HER2, including HER2-directed monoclonal antibodies. However, almost half of patients may not achieve a complete pathological response with these treatments, underscoring the need to investigate new therapeutic avenues that increase efficacy, reduce the risk of relapse and, at the same time, have less potential side effects to preserve the quality of life of patients,” he added.
DESTINY-Breast11 included 927 patients with high risk early-stage HER2+ breast cancer who had not previously received treatment, who were randomly assigned 1:1:1 to receive trastuzumab deruxtecan followed by the standard neoadjuvant triplet of dual HER2 blockade combined with chemotherapy or standard anthracycline-based chemotherapy followed by the same triplet combination, or trastuzumab deruxtecan monotherapy.
The investigators observed a pCR rate of 67.3% in patients who received the investigational combination with trastuzumab deruxtecan followed by the standard neoadjuvant triplet of dual HER2 blockade combined with chemotherapy compared with 56.3% in patients who were assigned to standard therapy. At data cutoff, treatment with the ADC combination showed an early favorable event-free survival (EFS) trend and an improved safety profile versus the standard anthracycline-based regimen.
“These data support this new treatment strategy as a potential new anthracycline-free regimen with improved efficacy and less toxicity for patients with high-risk HER2-positive early breast cancer,” concluded Escrivá de Romaní.
Trastuzumab deruxtecan (T-DXd) is approved in Spain for use as a second-line treatment for patients with advanced HER2+ breast cancer.
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Reference
*ESMO Congress 2025, 17 – 21 October, Berlin
Corresponding session details:
Date : 18 October, 2025
Chairs: Fabrice André (Villejuif, France) / Giuseppe Curigliano (Milan, Italy)
Room: Berlin Auditorium – Hub 27
Session time: 16:30 – 18:15 (CEST)
Abstract: 291O – DESTINY-Breast11: neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC)
Speaker: Nadia Harbeck (Munich, Germany)
Lecture time: 16:30 – 16:42 (CEST)
