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
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The Kaplan-Meier survival curve is defined as the probability of surviving in a given length of time while considering time in many small intervals.[3] There are three assumptions used in this analysis.
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In the survival analysis setting, landmark analysis refers to the practice of designating a time point occurring during the follow-up period (known as the landmark time) and analyzing only those subjects who have survived until the landmark time.1 A comprehensive overview of the landmark analysis method and its use has been provided by Dafni.2 To understand why landmark analysis is sometimes necessary, consider the following hypothetical example.
A study is conducted in which all subjects were treated at baseline and then followed for a period of several years. During follow-up, a subset of subjects were found to respond favorably to treatment, with response times varying among responders.
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PFS at pre-specified points in time—at 1-, 2- and 3-year “landmarks”—capture information about tumor control and time to disease progression, and such landmarks are easier for patients to understand than statistical measures, such as hazard ratios
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Mucositis occurs when cancer treatments break down the rapidly divided epithelial cells lining the gastro-intestinal tract which starts in the mouth , leaving the mucosal tissue open to ulceration and infection. The part of this lining that covers the mouth, called the oral mucosa, is probably the most common, debilitating complication of cancer treatments, particularly chemotherapy and radiation. . It has a significant effect on the patient’s quality of life and can be dose-limiting (i.e., requiring a reduction in subsequent chemotherapy doses).
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Proteins that help the body produce white blood cells. They are also called CSFs which is an acronym for blood-forming, colony-stimulating factors. White blood cells help fight infection and can be destroyed during some types of cancer treatment.
Having low numbers of white blood cells is called neutropenia. People with neutropenia are more likely to develop infections. Some people with neutropenia develop a fever, called febrile neutropenia, and some do not. Febrile neutropenia may be a sign of an infection. A person with febrile neutropenia may need antibiotics and to stay in the hospital until the infection is gone.
. CSFs are given as shots, usually 24 hours after a chemotherapy treatment, Neupogen, Leukine and Neulasta. These medications are made in the laboratory and are similar to those naturally produced by the body.
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
Stephanie Lynn Graff, MD, FACP
Dr. 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. In Dr. Graff is 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 is a PI on numerous clinical trials in addition to her work in translational research, genomics, and gender bias.
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.”
Ultimately, Dr. Graff is passionate about connecting with her patients to provide personalized, comprehensive oncology care, advancing breast cancer research, and breast cancer prevention.
Hope S. Rugo, MD, FASCO
Dr. Rugo is a medical oncologist and hematologist specializing in breast cancer research and treatment. A Professor of Medicine, Dr. Rugo joined the Breast Care Center in 1999 after a decade of experience at University of California San Francisco (UCSF) in malignant hematology and bone marrow transplantation for a variety of diseases, including breast cancer. She entered the field of breast cancer in order to incorporate novel therapies based on an understanding of the biology of cancer with excellent quality of care into the treatment of women with breast cancer. Dr. Rugo is the Director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center. She is a principal investigator of multiple clinical trials focusing on combining novel targeted therapeutics with standard treatment to improve the treatment of both early and late stage breast cancer and has published widely in this area. Her current research interests include immunotherapy and combinations of targeted agents in the treatment of breast cancer to overcome resistance. In addition, Dr. Rugo has conducted a number of studies focusing on reducing toxicity from therapy, resulting in approval of scalp cooling to reduce chemotherapy induced hair loss, and a steroid mouthwash to reduce targeted agent stomatitis. She is an investigator and the chair of the Safety Committee for the multicenter adaptively randomized phase II I-SPY2 trial, and also serves on the Novel Agents Committee. Dr. Rugo is the co-chair of the Triple Negative Working Group and an active member of the Translational Breast Cancer Research Consortium (TBCRC) and is the principal investigator of several TBCRC trials including a multi-center immunotherapy trial funded by the Breast Cancer Research Foundation (BCRF). She is an active member of the Alliance (formerly CALGB) Breast Committee, as well as ASCO, where she serves on the Guidelines Committee and as an editor for the Education Committee. In addition to her research, Dr. Rugo is an active clinician, and is committed to education, regularly lecturing locally, nationally, and internationally on subjects relating to the treatment of and supportive care for breast cancer. At UCSF, Dr. Rugo runs the Breast Forum, an open bimonthly evening educational session for breast cancer patients, families, and friends from throughout the bay area. Dr. Rugo graduated from the University of Pennsylvania School of Medicine in 1983. She completed a residency in internal medicine and primary care followed by a fellowship in hematology and oncology at the University of California San Francisco. She was a post-doctoral fellow in immunology participating in laboratory research at Stanford University from 1988-1990. In 1990, Dr. Rugo joined the faculty at UCSF in the Division of Hematology and Oncology. Dr. Rugo has been recognized for her excellence in both patient care and in teaching of both medical students and training physicians. She has received several awards including the Bank of America Giannini Foundation Award and a UCSF Clinical Cancer Center Investigator Research Program intra-mural award. In 2006, she was honored for her work in Breast Cancer Research by the Friends of the Breast Care Center.
