Zynyz: A New Drug for Merkel Cell Carcinoma
- A new immunotherapy drug has been given accelerated approval as a treatment for patients with metastatic or recurrent locally advanced Merkel cell carcinoma.
- Merkel Cell Carcinoma is an aggressive and rare type of skin cancer.
- Zynyz is an intravenous PD-1 inhibitor, a type of immunotherapy, which stimulates the immune system to find the cancer cells and attack them.
- 52% of patients responded to treatment with Zynyz: 18% had their lesions disappear and 34% had their lesions shrink in size by a certain amount.
- Earlier approval of drugs that treat serious conditions can happen because of FDA's Accelerated Approval Program.
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Zynz is a drug called an immune checkpoint inhibitor, which works by specifically targeting proteins found either on immune or cancer cells and preventing them from binding together.
The approval was based on the results of a study called PODIUM-201 (NCT03599713), an open-label, multiregional, single-arm study evaluating 65 patients with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for advanced disease.
Dr. Bhatia is the principal author of the study and director of the Melanoma and Renal Cancer Team at Fred Hutch Cancer Center
“The approval of Zynyz offers healthcare providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease,” Dr. Bhatia added.
Some people in the study had surgery or radiation for their condition before treatment with this new drug. But none of the 65 people in the initial assessment received prior therapies like chemotherapy.
The study measured the number of people treated with Zynyz who saw their Merkel cell carcinoma lesions disappear (what experts call complete response) or shrink in size by a certain amount (partial response).
It was demonstrated that 52% of patients responded to treatment:
- 18% had a complete response (12 out of 65 patients).
- 34% presented partial response (22 out of 65 patients).
A secondary measurement of the study was what experts call duration of response, or how long the response to treatment lasts. The duration of response ranged from 1.1 to 24.9 months.
The authors of the trial showed that:
- 76% of patients who responded, had a response that lasted 6 months or more.
- 62% of patients who responded, had a response that lasted 12 months or more.
Study participants received an intravenous dose of Zynyz (500 mg) every four weeks for up to 24 weeks or until disease progression or unacceptable toxicity.
More on Merkel Cell Carcinoma
Merkel cell carcinoma is an aggressive and rare type of skin cancer that usually appears as a single, painless, flesh-colored or bluish-red nodule, often on your face, head, neck and arms (skin exposed to sunlight).
It tends to grow quickly and has a high rate of metastatic disease.
At the time of diagnosis, the lesions are usually smaller than 20 mm, and most cases show rapid tumor growth in a few months.
It usually occurs in elderly patients, in chronically sun-exposed areas or in patients with a weak immune system, such as transplant recipients, patients with lymphoproliferative neoplasms (disease of the lymphatic system), or patients with human immunodeficiency virus (HIV).
As mentioned, age is an important risk factor:
- 90% of all patients with MCC are aged over 50 years
- 76% are over 65 years
- 49% are over 75 years.
The estimated five-year overall survival rate for people with distant metastatic MCC is 14%.
Surgery is the initial treatment for most cases of MCC. The goal of surgical treatment is to resect (remove) the whole lesion with margins of 1 -2 cm.
Radiotherapy also plays an important role in the treatment of MCC and may be considered as primary therapy in patients who are not candidates for surgery.
The use of radiotherapy after surgery (known as adjuvant radiotherapy) remains controversial. It appears to increase local tumor control but has no significant impact on tumor-related overall survival.
Diagnosis of MCC
Diagnosis can be obtained with the following tests or procedures:
- Physical exam: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual.
- Health history: A documented history of the patient's health habits and past illnesses and treatments.
- Full-body skin exam: A doctor or nurse checks the skin for bumps or spots that look abnormal in color, size, shape, or texture. The size, shape, and texture of the lymph nodes will also be checked.
- Skin biopsy: The removal of skin cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
Self Awareness Is Essential
Dr. Cecilia Larocca, a dermatologist at Dana Farber Cancer Institute, told SurvivorNet in a previous interview that she typically recommends people do a self-exam on their skin once a month and look for any new or changing moles or spots.
"The most important thing to do whenever you have a mole that you're worried about is to get it evaluated," Dr. Larocca said.
"When we evaluate a mole, it's also very important for us to get a good sense of what your family history is, and your sun exposure history,” she said.
“So when you come into a dermatologist, often we'll ask several questions to get a sense of your risk factors â€¦ any family history of melanoma, any history of tanning bed use, and history of tanning sunburns."
The best tool we have for detecting skin cancer early is our eyes. If you see something new, unusual, or changing, get it checked because it could save your life.
FDA’s Accelerated Approval Program
The U.S. Food and Drug Administration granted accelerated approval to Zynyz for metastatic or recurrent locally advanced Merkel cell carcinoma. Earlier approval of drugs that treat serious conditions can happen because of FDA's Accelerated Approval Program.
With accelerated approval, drug companies are still required to conduct studies to confirm the anticipated clinical benefit. But if the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug.
If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.
What Is a PD-1 Inhibitor?
Zynyz is an intravenous PD-1 inhibitor, a type of targeted therapy. Immunotherapy drugs specifically target proteins found either on immune or cancer cells to prevent their binding together. PD-1 is one of these proteins.
The advent of these drugs in treating cancer is that it doesn't kill cancer cells directly, but it stimulates the immune system to find the cancer cells and attack them while hopefully not affecting other surrounding healthy cells.
They work on the background knowledge that the immune system can protect our bodies by getting rid of any foreign cell that isn't produced in the body.
It sets out to do this by identifying specific proteins (also known as checkpoint proteins) that are only found on normal cells. When it finds them, it binds to this cell to mark it as safe and leave it be.
PD-1, referred to as programmed cell death 1, is a protein that is found on the outer surface of cells in your immune system. PD-L1, referred to as programmed cell death ligand, is on the outer layer of some normal blood cells, as well as some cancer cells.
When PD-1 binds to PD-L1, this puts the brakes on the immune system and can prevent immune cells from attacking and killing cells.
Normally, this acts as a braking mechanism to prevent our immune systems from becoming overactive and going somewhat haywire by attacking our normal cells. Cancer cells can take over or override this innate mechanism, preventing cancer cells from dying.
What Are the Risks of This Treatment?
As any drug that fights cancer, Zynyz can cause serious side effects. Serious adverse events occurred in 22% of patients and 11% of patients discontinued treatment because of serious adverse events.
The most common side effects are:
- Irregular heartbeat (arrhythmia)
- Lung inflammation (pneumonitis)
- Muscle and bone pain
Your care team will make sure you are eligible to receive it. Some reasons not to receive this new drug (contraindications) are:
- Having immune system problems such as Crohn's disease, ulcerative colitis, or lupus
- Being an organ transplant receiver
- If you plan to receive a stem cell transplant that uses donor stem cells (allogeneic transplant)
- Previous history of radiation therapy to your chest area
- Having neurologic conditions such as myasthenia gravis or Guillain-BarrÃ© syndrome
- Being pregnant, planning to become pregnant or if you are breastfeeding. It is not known if Zynyz passes into your breast milk
Questions to Ask Your Doctor About Zynyz and Merkel Cell Carcinoma:
- Am I eligible to receive Zynyz?
- What side effects might I expect from immunotherapy?
- What will my treatment cost?
- Will my treatment be covered by my medical insurance company?
- Should I get a second opinion?