In patients with unresectable Her2+ and/or metastatic breast cancer, previously treated with anti-Her2 therapies (trastuzumab or a taxane), trastuzumab deruxtecan (T-DXd) improved overall survival in a statistically and clinically significant way with a reduction of 36 % risk of death and 22-month progression-free survival compared with trastuzumab emtansine (T-DM1). These are the updated results of the DESTINY-Breast03 phase 3 study and the primary analysis of the DESTINY-Breast02 phase 3 study presented today at the San Antonio Breast Cancer Symposium (#SABCS) underway in Texas (USA), with the simultaneous publication of the updated data of DESTINY-Breast03 in The Lancet.
Trastuzumab deruxtecan is a drug-conjugated monoclonal antibody specifically engineered to target the Her2 receptor, explains a statement jointly released by Daiichi Sankyo and AstraZeneca, which developed and marketed the treatment.
“Patients with Her2 positive metastatic breast cancer, subjected to previous therapies, in the majority of cases undergo disease progression in less than a year – explains Giuseppe Curigliano, professor of Medical Oncology at the University of Milan and director of the Development Division of new drugs for innovative therapies at the European Institute of Oncology in Milan -. There is a substantial and consistent benefit across all key efficacy endpoints in patients receiving trastuzumab deruxtecan in DESTINY-Breast03, a study that included 524 patients with metastatic Her2+ breast cancer previously treated with trastuzumab and chemotherapy. T-DXd significantly reduced the risk of death compared with T-DM1, another Her2 antibody conjugate and previous standard of care. This benefit has also been seen in women with brain metastases. Not only. The superiority of T-DXd also emerged in terms of objective responses and disease control”.
With additional follow-up in DESTINY-Breast03, T-DXd demonstrated a clinically meaningful improvement in median progression-free survival (PFS) of 22 months compared to T-DM1, reaffirming the statistically significant result from the previous interim analysis (28 .8 months with T-DXd versus 6.8 months with T-DM1). The confirmed objective response rate (ORR) was 78.5% in the T-DXd arm, with 21.1% of patients achieving a complete response (CR), compared with an ORR of 35.0% in the T-DM1 arm, where 9.5% of patients achieved a CR. The median duration of response (DoR) was 36.6 months for T-DXd versus 23.8 months for T-DM1.
“In the DESTINY-Breast01 study, trastuzumab deruxtecan had demonstrated an important and long-lasting antitumor activity in heavily pretreated Her2+ patients, supporting the rationale of the DESTINY-Breast03 study which mainly included patients in second line therapy – underlines Giampaolo Bianchini, head of the Breast Group , Oncology Department of the Irccs San Raffaele Hospital in Milan -. In this study, progression-free survival quadrupled from reference therapy to 28.8 months, an improvement of nearly 2 years. An advantage never seen before in breast cancer, also associated with a significant improvement in survival. Trastuzumab deruxtecan – he adds – is a candidate as a new standard of care for patients in second-line therapy for Her2-positive metastatic breast cancer”.
In the phase 3 study DESTINY-Breast02, in patients with Her2+ unresectable and/or metastatic breast cancer previously treated with T-DM1, compared with chemotherapy (trastuzumab plus capecitabine or lapatinib plus capecitabine), second-line T-DXd also demonstrated a 64% reduction in the risk of disease progression or death (34%) and a significant improvement in progression-free survival (17.8 months vs 6.9 months).
“The DESTINY-Breast02 study also underlines the role that trastuzumab deruxtecan will have as a treatment for women with metastatic breast cancer – explains Valentina Guarneri, director of Oncology 2 of the Veneto Oncological Institute Irccs of Padua and full professor of Medical Oncology at the University of Padua -. Trastuzumab deruxtecan nearly tripled progression-free survival to 17.8 months compared with 6.9 months in patients receiving the investigator’s choice of therapy. Results that confirm the efficacy of this class of drugs with a molecular target, which have already demonstrated results of extreme clinical interest even in the earliest stages of the disease”.
In all studies presented, the safety profile of the most common adverse events with trastuzumab deruxtecan was consistent with previous clinical studies and no new safety signals were identified.
“In 2020, around 55,000 new cases of breast cancer were estimated in Italy, the most frequent neoplasm in the entire population – concludes Saverio Cinieri, president of the Italian Association of Medical Oncology -. Today, in cases where overexpression of the Her2 receptor is present, it is possible to use highly effective drugs which selectively target the diseased cells thus sparing the healthy ones. This is the case of conjugated antibodies, such as trastuzumab deruxtecan, an innovative therapy which in the second-line treatment of patients with Her2 positive metastatic carcinoma is able to control the disease, improve quality of life and delay the time to clinical deterioration”.
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