The Future of Antibody Drug Conjugate Padcev in Breast Cancer
- Research presented at this year’s American Society of Clinical Oncology (ASCO) conference showed that a drug called Padcev (enfortumab vedotin) had some effect treating women with advanced breast cancer who had undergone previous treatments — but the results fell short of the clinical trial’s goals.
- Padcev is a type of drug known as an antibody drug conjugate, which is a type of immunotherapy for cancer. So far, Padcav has only been approved for use in urothelial cancer (cancer that begins in the urothelial cells, which are found in the urethra, bladder, ureters, and renel pelvis).
- These results of the breast cancer trial are disappointing, but perhaps not the final word on Padcev for the treatment of metastatic, or advanced, breast cancer — as researchers look for other ways to use the drug.
At this year's
ASCO (American Society of Clinical Oncology) annual meeting ,
researchers announced that a drug called enfortumab vedotin (brand name:
Padcev ) showed anti-tumor activity in women with
advanced breast cancer who had already tried several treatment approaches. However, the drug was not as effective as researchers hoped. The women in the study were "heavily pre-treated," which means they had undergone multiple lines of therapy for their disease, often including surgery, radiation, chemotherapy, targeted therapy, immunotherapy, or other treatments. These patients typically have a history of several different treatment regimens due to the persistence, progression, or recurrence of their cancer.
The Future of Padcev
The study, the EV-202 phase II clinical trial, tested women who had two different types of advanced breast cancer — hormone receptor-positive (HR+), HER2 negative breast cancer and triple negative breast cancer. These trial results are disappointing, but perhaps not the final word on Padcev for the treatment of metastatic breast cancer. Researchers plan to look at other ways this drug, which has been effective in urothelial cancer, can be used. Stage four, or metastatic, breast cancer means that cancer has spread to distant areas of the body. It is no longer regionalized to the breast. And while there is no cure for metastatic breast cancer, doctors have a lot of options to treat this stage of advanced disease. One advantage to being such a common cancer is that breast cancer has been the focus of much research. Currently, Padcev is only approved for use in urothelial cancer (cancer that begins in the urothelial cells, which are found in the urethra, bladder, ureters, and renel pelvis). It is not approved for treating breast cancer.
Why Does Type Matter in Breast Cancer?
Triple-negative breast cancer (TNBC) is a type of breast cancer that is characterized by the absence of three common receptors known to fuel most breast cancer growth: estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2). Knowing what type of breast cancer you have is critical to making a treatment plan, as different types tend to respond better to specific treatment approaches.
Triple Negative Breast Cancer vs. HER2-low Breast Cancer
What may have previously been diagnosed as triple negative breast cancer may now be classified as HER2-low (instead of HER2-negative). Breast cancer cells with higher-than-normal levels of HER2 are called HER2-positive, those with low levels of HER2 are (or were) called HER2 negative. Recently, however, researchers have looked to further expand this definition to include patients that have a minimal amount of HER2 expression but do not meet the classic definition for HER2-positive tumors. This group has been called HER2 "low" and is very important as it represents almost 50% of all patients with breast cancer. Therefore, it is exceedingly important to discuss with your physician about your HER2 status.
Why is Triple Negative Breast Cancer Harder to Treat?
Some of the most effective drugs for breast cancer target common characteristics that help many breast tumors grow. Those characteristics are tumors that have the HER2 gene, estrogen receptors or progesterone receptors. Triple negative breast cancers have none of these. Targeted drugs are available to treat HER2+ breast cancers as well as estrogen-receptor and progesterone-receptor positive breast cancer. "Triple-negative breast cancer has historically been the hardest and most aggressive cancer to treat because we don't have the same targeted therapies like we use for HER2 positive disease or hormone-receptor positive disease."
Dr Elizabeth Comen , a medical oncologist who specializes in breast cancer at
Memorial Sloan Kettering Cancer Center in New York, told SurvivorNet in a previous conversation.
Dr. Elizabeth Comen explains why triple negative breast cancer is harder to treat. What's the Data on Padcev?
The
EV-202 phase II clinical trial tested Padcev in 87 participants with locally
advanced or metastatic breast cancer. - 45 had hormone receptor-positive, HER2-negative breast cancer
- 42 had triple-negative breast cancer
- All patients included were heavily pre-treated women with advanced breast cancer (meaning that they had undergone multiple lines of therapy for the disease)
The study tracked how well the cancer responded to Padcev. The results showed:
- Seven (15.6%) of the participants with hormone receptor-positive, HER2-negative breast cancer saw some response
- Eight people (19%) of the the triple-negative breast cancer group had slightly better results
However, these results did not meet the trial goals of 12 out of 40 responders in the hormone receptor-positive group and 10 out of 40 responders in the triple-negative breast cancer group. The average time without cancer growing or spreading was:
- 5.4 months for the hormone receptor-positive group
- 3.5 months for the triple-negative breast cancer group
What is an Antibody Drug Conjugate?
Padcev is a type of drug known as an antibody-drug conjugate, which essentially means that a combination of two different types of drugs work together to target cancer.
Dr. Debasish Sundi , a urological oncologist at the
Ohio State University Comprehensive Cancer Center in Columbus, told SurvivorNet in a previous conversation that with an antibody drug conjugate, "there's an antibody that's designed to recognize a specific cancer-related protein. And we call it an antibody drug conjugate because the antibody is kind of used as a homing missile, if you will, against the cancer cell, and is conjugated (hence the name) or connected to another medicine." This is like the payload that actually kills the cancer cells, he said. Antibody drug conjugates are composed of three different components:
a monoclonal antibody (mAb) and a cytotoxic payload made from a chemotherapy agent, which are connected together using a chemical linker. Padcev is approved for use in urothelial cancer, but oncologists believe it might also be effective against certain types of solid tumors, like breast cancer lesions. Though, as the recent study indicated, more research and fine-tuning is needed.
Padcev Side Effects
Like any cancer treatment, Padvec can come with side effects, but there are often a number of things you can do to manage them. Talk to your care team about these recommendations. They can help you decide what will work best for you. Some noted side effects include:
- Skin changes, like rashes, dry skin or itching
- Numbness or tingling in the hands and/or feet (known as peripheral neuropathy)
- Feeling of constant tiredness (fatigue)
- Decrease in appetite or taste changes
- Loss or thinning of scalp and body hair (alopecia)
- Eye problems such as blurry vision and dryness
- Upset stomach, nausea or vomiting
- Diarrhea
- Low red blood Cell Count (anemia)
- Low White Blood cell count (leukopenia or neutropenia)
Less common, but important side effects can include:
- High Blood Sugar: padcev can raise blood sugar levels in both diabetic and non-diabetic patients. Your oncology care team will keep an eye on your blood sugar levels. If you experience increased thirst, urination, hunger, blurry vision, headaches, or fruity-smelling breath, inform your healthcare team immediately. Diabetic patients should monitor their blood sugar closely and report any increases to their healthcare team.
- Pneumonitis: it can algo cause lung inflammation (pneumonitis). Contact your oncology care team immediately if you notice any new or worsening symptoms such as shortness of breath, difficulty breathing, cough, or fever.
Questions to Ask Your Doctor
- How is my cancer classified?
- Are there new treatment approaches available for my disease?
- Should I consider a clinical trial?
- What side effects are associated with my treatment path?
- How are these side effects managed?
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