Antibody-drug conjugates (ADCs) aim to improve the therapeutic index of systemic chemotherapy through targeted delivery to cancer cells, improved efficacy, and decreased toxicity.
In a presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Reshma Mahtani, DO, chief of breast oncology at Miami Cancer Institute, part of Baptist Health South Florida, described ADCs as the "new Trojan horses in oncology."1
An active clinical researcher, Dr. Mahtani advances the landscape of ADCs to bring novel breast cancer treatments and clinical trials to patients in South Florida and beyond.
She recently co-authored an abstract presented at European Society for Medical Oncology (ESMO) Congress 2022 regarding patient reported outcomes from the phase 3 DESTINY-Breast04 study which compared the safety and effectiveness trastuzumab deruxtecan (T-DXd) with the treatment of a physician's choice (TPC).2-4
This ADC is made of an antibody that targets human epidermal growth factor receptor 2 (HERZ), which brings the chemotherapeutic DXd directly to HERZ-expressing tumors.5 T-DXd therapy attacks and destroy cancer cells that over express HERZ as well as cancer cells in the surrounding tissue with low levels of HERZ expression.6
T-DXd has been approved in several countries for the treatment of HERZ+ breast cancer and gastric cancer. In the United States it is approved to treat HERZ-positive breast cancer and was recently also approved for HERZ low metastatic breast cancer. In addition it is approved for locally advanced or metastatic HERZ+ gastric cancer, and HERZ-mutant lung cancer.7-9
"The approval of T-DXd for the treatment of HERZ-low metastatic breast cancer will have a significant positive impact on a large percentage of patients," says Dr. Mahtani. "This is the first approved therapy for HERZ-low breast cancer and will provide an important new targeted therapy option for many patients."
Patients enrolled in DESTINY-Breast04 had breast tumors that were metastatic, had low expression levels of the HERZ protein (HERZ-low), were considered refractory to endocrine therapy, and had been treated with 1-2 lines of chemotherapy in the past.2-4
Researchers found that patients with HERZ-low metastatic breast cancer who were treated with T-DXd had significantly longer progression-free survival (10.1 months vs 5.4 months) and overall survival (about 6 months longer) compared with patients treated with treatment of physicians choice (TPC).2
Side effects of T-DXd were consistent with those seen in previous studies in patients with HERZ+ metastatic breast cancer, with the most common being nausea and fatigue. Some serious, in some cases fatal side effects include interstitial lung disease (ILD), pneumonitis, heart problems, neutropenia, and harm to a fetus.3,10
The oncologic specialists at the Miami Cancer Institute are members of one of nine tumor site teams, and each Cancer Institute team is led by a dedicated physician and supported by highly trained clinical research staff. Teams collaborate closely with colleagues at Memorial Sloan Kettering Cancer Center, along with a partnership in the Memorial Sloan Kettering Cancer Alliance. These partnerships and collaborations in novel clinical trials mean the Cancer Institute offers you and your patients access to a broad range of leading-edge clinical trials - facilitating access to potentially promising new therapies not yet available to the general market.
Ongoing clinical trials examining T-DXd in patients with HERZ-low breast cancer include:
- Mahtani, R. Expanding the landscape of antibody-drug conjugates: new trojan horses in oncology. Oral presentation at: American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.
- Ueno NT et al. Presented at ESMO 2022; September 9-12; Paris, France. Poster Presentation 2170.
- Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HERZ-low advanced breast cancer. N Eng! J Med. 2022;387(1):9-20.