Five Advocate Chats were presented as part of the Alamo Breast Cancer Foundation’s Advocate Program (AAP) during the 2020 San Antonio Breast Cancer Symposium. In one of these chats, I interviewed Richard Crownover, M.D., Radiation Oncologist at the University of Arkansas Medical Science College of Medicine. In this chat, Dr. Crownover covered a lot of information regarding new and existing radiation treatments. However, several radiation treatment studies were not covered due to lack of time. I’ve researched these topics and provide follow-up information in the following report.
COMET stands for Comparison of Operative to Monitoring and Endocrine Therapy for low-risk ductal carcinoma in situ (DCIS). The COMET trial is the first large phase III randomized clinical trial in the United States to look at management strategies for low-risk DCIS patients. Approximately 1200 women will be enrolled in this multi-center trial that will be conducted in 100 cancer centers throughout the United States. The study is funded by the Patient-Centered Outcomes Research Institute (PCORI).
Why Study Is Needed
Surgery, radiation, and endocrine therapy are considered standard of care for DCIS, the same treatments that are indicated for invasive breast cancer. Both surgery and radiation have potential side effects. The side effects of surgery could consist of pain, infection, scarring, loss of feeling depression and anxiety. Radiation side effects can be very serious and include damage to lungs, heart, thyroid, bones, joints and other organs, as well as increased risk of other cancers.
Some studies have shown that DCIS may never become invasive breast cancer even without treatment. These studies have caused clinicians and researchers to question if patients diagnosed with DCIS are being overtreated. The purpose of the COMET study is to find evidence that DCIS patients may have excellent outcomes with active surveillance. The study will provide information to better understand low-risk DCIS.
The COMET study will look at two different interventions for DCIS. Patients will be randomized to one of these two groups:
Standard care: This is likely to include surgery (lumpectomy or mastectomy) and possible radiation therapy. Follow-up exams are every six months with yearly mammograms.
Active surveillance: This includes mammograms and physical exams every six months.
The COMET study may show that active surveillance is equally as safe and effective as surgery for women with low-risk DCIS.
FDA Approval of Tucatinib Provides Patients with HER2 Positive Brain Metastasis Another Treatment Alternative
HER2 Positive breast cancer patients with brain metastasis now have another treatment option besides partial or whole brain radiation. Tucatinib in combination with trastuzumab and capecitabine was approved by the FDA on April 12, 2020 for adult patients with unresectable or metastatic HER2 positive breast cancer. This includes patients with brain metastasis who have received one or more prior anti-HER2-based regimens in the metastatic setting.
The most common adverse reactions for Tucatinib were diarrhea, nausea, palmer-plantar erythodysesthesia, fatigue, hepatotoxicity, vomiting, stomatitis, decrease appetite, abdominal pain, headache, anemia, and rash.
Side effects for whole brain radiation are cognitive changes, such as memory problems,
immediate recall, and verbal fluency.
Stereotactic Ablative Radiotherapy in Oligometastatic Breast Cancer
Recent studies have shown that there is increased interest in the use of radiation therapy in selected cases of breast cancer presenting as oligometastatic (occurring in a small number of metastatic sites). Preliminary evidence indicates that radiation-based treatments can play an important role in the management of metastatic breast cancer patients. Stereotactic radiotherapy offers an effective non-invasive approach to ablate breast tumors in the brain, bone, or other sites. It may also be more cost effective and potentially improve clinical outcomes with minimal toxicity.
The SABER trial is a Phase I Study to Evaluate the Safety and Feasibility of Preoperative Ablative Breast Radiotherapy (SABER)
The purpose of the SABER study is to determine the most effective dose of radiation therapy to treat breast cancer tumors in a shorter period of time, prior to standard partial mastectomy/axillary surgery. Eighteen patients will be enrolled. The study started on August 5, 2020, and its completion date is August 2025.
Study Design (two components):
Experimental: Preoperative Stereotactic Ablative Breast Radiotherapy (SABER) testing up to 4 dose levels.
Non-experimental: Participants will undergo standard partial mastectomy and axillary surgery after preoperative SABER is completed.
Participants will be treated with an assigned dose level of preoperative SABER, delivered once a day, 5 fractions given on non-consecutive days over a period of 2 weeks. In the Phase I study, starting with dose level II, a dose level of preoperative SABER will be assigned per study dose-escalation design, treating 2 to 6 patients per dose level. The tested doses are the following:
Dose Level 1: 35 GY (5 fractions of 7 Gy)
Dose Level II (Starting Dose): 40Gy (5 fractions of 8 Gy)
Dose Level III: 45Gy (5 fractions of 9 Gy)
Dose Level IV: (50Gy (5 fractions at 10 GY)
Primary Outcome Measures:
The recommended Phase II Dose (RP2D) of pre-operative SABER will be established as the highest dose level tested for which not more than 1 out of 6 patients experience dose-limiting toxicity or adverse events.
Secondary Outcome Measures:
Number of participants experiencing treatment related toxicity by type and grade including adverse events, and serious adverse events and dose-limiting toxicities.
Percentage of participants with Complete Pathological Response.
Participant cosmesis will be evaluated by a physician at 1,6,12 and 24 months post treatment up to 2.5 years.
Participant reported health related quality of life. Time frame: 1,6,12 and 24 months.
50 years and older
Estrogen-receptor, progesterone-receptor positive and HER2 negative
Unifocal breast cancer
Patients without histologically confirmed invasive breast cancer
Patients with metastatic disease
Patients that are unable to undergo MRI
Patients with prior history of radiation to the chest
Patients unable to consent, pregnant or nursing, or prisoners