ASCO 2022: When the Dust Settles, Will ADCs Change MBC?
While the DESTINY-Breast04 trial, which earned a standing ovation as a practice-changing study for treatment of HER2-low MBC garnered most of the headlines from the ASCO (American Society of Clinical Oncologists) annual meeting in June, it was not the only reason for optimism. In this episode Our MBC Life’s Victoria Goldberg and Lynda Weatherby continue to explore what the research shared at ASCO means for us, the patients living with MBC.
You’ll hear from preeminent oncologists Stephanie Graff, Director of breast oncology at the Lifespan Cancer Institute at Brown University and Hope Rugo (Professor, Department of Medicine (Hematology/Oncology) and Director, Breast Oncology and Clinical Trials Education, UCSF) in this deep dive into two critical studies: DESTINY-Breast04 and TROPiCS-02, which examined a potential new line of treatment for heavily pre-treated HR-positive, HER2-negative MBC patients.
Enhertu (trastuzumab deruxtecan )and Trodelvy (sacituzumab govitecan), the two drugs at the heart of these two trials are both representatives of a relatively new class of drugs: Antibody Drug Conjugates—ADCs. ADCs are a class of drugs that links a potent chemotherapy drug with an antibody. Unlike traditional chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. They are a kind of “smart bomb” for cancer treatment—and an extraordinarily promising development for patients.
Our wide-ranging conversations with Dr. Graff and Dr. Rugo cover not only the results of these two trials, but their specific implications for treatment and the future of breast cancer research.
Additional Resources
Musings of a Cancer Doctor Breast Cancer at ASCO 2022, Sledge, George W. Jr. MD, Oncology Times: July 20, 2022 - Volume 44 - Issue 14 - p 18-19
”Trastuzumab deruxtecan, one suspects, will rapidly become a new standard of care in the HER2-low population, though important questions remain regarding its use. In particular, the number of patients with so-called triple-negative breast cancer was relatively small, and while there was no obvious difference between the ER-positive and triple-negative outcomes, more data would certainly be helpful. And, given the emergence of another ADC, sacituzumab govitecan, in the triple-negative space, we will need greater nuance regarding best treatment options in triple-negative-no-longer subgroups. Undoubtedly, we will be subjected to marketing campaigns saying “my ADC is better than your ADC" in the absence of head-to-head comparisons. Given the somewhat scary interstitial lung disease seen with trastuzumab deruxtecan, physicians will need improved management skills with these promising yet toxic agents. “
Glossary
Novel Therapies Mentioned in the Episode
Trastuzumab Deruxtecan (Enhertu or TdxD)
Neratinib (Nerlynx)
Sacituzumab Govitecan (Trodelvy)
Datopotamab deruxtecan (Dato-DXd)
Clinical Trials Mentioned in this Episode
Phase 3 DESTINY-Breast03 study (NCT03529110)
Phase 3 DESTINY-Breast04 Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low MBC (NCT03734029)
Platform Phase 1b/2 DESTINY-Breast07 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer (includes active brain mets arm) (NCT04538742)
Phase 3 TROPiCS-02 study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer(NCT03901339)
Phase 2 Study Scalp Cooling in MBC done to compare rates of hair loss of people with metastatic breast who use scalp cooling versus those who do not use scalp cooling after receiving standard of care treatment with either sacituzumab govitecan, trastuzumab deruxtecan, or eribulin (NCT04986579
Phase 3 TROPION-Breast02 Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (NCT05374512)
Want More?
If you have not done so already, listen to our past interviews with the guests of this episode as well as ASCO 2022-related content.
Meet the Guests of this Episode
Growing up in a small farming community in rural Missouri, Stephanie Lynn Graff, MD, FACP was the first in her family to attend college. Because she was drawn to science from a young age, she enrolled in a 6-year medical program right out of high school. As she progressed from medical school to residency to a fellowship, she was fascinated by every aspect of the science of oncology—including cell biology and pharmacology.
Dr. Stephanie Graff is the Director of Breast Oncology at Lifespan Cancer Institute at the Legorreta Cancer Center at Brown University in Providence, Rhode Island. Dr. Graff serves as co-lead of the Breast Cancer Translational Research Disease Working Group at Brown University and is an Assistant Professor of Medicine at the Warren-Alpert School of Medicine. Prior to joining the team at Lifespan/Brown, she was Director of both the Breast Program and Clinical Research at the Sarah Cannon Cancer Institute at HCA Midwest, as well as Associate Director of the Breast Cancer Research Program at Sarah Cannon Research Institute and National Breast Lead for the Sarah Cannon Cancer Network’s clinical programs. In addition, Dr. Graff serves as a medical advisor to the Dr. Susan Love Foundation for Breast Cancer Research.
Dr. Graff is board certified in Medical Oncology, Hematology, and Internal Medicine; and completed a breast oncology sub-fellowship at the University of Kansas. Dr. Graff has broad experience as a Principal Investigator on numerous clinical trials across all phases of drug development, in addition to work in translational research, genomics, and gender bias. In addition to scientific publications, she is an award-winning writer, social media influencer, and sought-after public speaker. Dr. Graff has received the Frist Humanitarian Award for her work in the community and the Benjamin L. Sapers Memorial Award for her “passion for pedagogy, academic rigor, empathy and humanism, with profound feeling for the person as patient.” Dr. Graff currently serves on the American Cancer Society Rhode Island Leadership Council and actively volunteers in the American Society of Clinical Oncology, where she is a 2020 graduate of the prestigious ASCO Leadership Development Program, and now serves on the Joint Certifications Committee and Women In Oncology Work Group. Ultimately, Dr. Graff is passionate about connecting with her patients to provide personalized, comprehensive oncology care, advancing breast cancer research, and breast cancer prevention.