For your patients: New options, better outcomes for advanced melanoma

Unresectable or metastatic melanoma refers to tumors that cannot be removed surgically or that have spread to distant sites in the body. A melanoma may be undetectable for a number of reasons, including the location or the patient’s general health or preference.

Non-resectable melanoma includes some stage III lesions, while distant metastatic lesions are all stage IV. Recent advances in pharmacological treatment of melanoma are helping more patients with advanced skin cancer to live longer and more productive lives.

Metastatic melanoma may be limited to a few sites or be diffuse (metastatic). Surgery remains an option for many patients with limited metastatic melanoma. If the disease has spread to many distant sites, drug therapy is usually the first option.

Basic approach to treatment

Historically, surgery has had a limited role in treating non-resectable/metastatic melanoma compared to early stage disease. Chemotherapy constituted the basis of treatment for most patients. Over the past two decades, new non-chemotherapy drugs have emerged to replace traditional chemotherapy. Based on a better understanding of cancer biology, newer drugs are generally more effective and better tolerated than chemotherapy.

In some cases, drug treatment can shrink unresectable tumors and make surgery possible. When surgery is possible for limited metastatic melanoma, the patient may also receive drug therapy after surgery, which is called adjuvant therapy.

Radiation therapy for melanoma is primarily used to relieve pain and other symptoms associated with cancer.

targeted therapy

As the name implies, targeted drugs are used in specific processes involved in the formation and development or targeting of cancer. In the case of melanoma, available targeted therapies are specific to a defect in a gene called . BRAF. Up to half of all melanomas have it BRAF leap.

Two drugs are used together to prevent an abnormal protein caused by a mutation BRAF gene. Three different combinations of two drugs have been approved in the United States for treatment BRAFPositive melanoma: dabrafenib (Tafenlar)/trametinib (Mykinest), vemurafenib (Zelboraf)/copemetinib (Kotelic), incourafenib (Pravtovi)/benemetinib (Miktofi). A single anti-BRAF drug is rarely used alone.

Immune checkpoint inhibitors (ICIs)

ICIs are the most commonly used drugs in the initial treatment of advanced melanoma. The improved survival in non-resectable/metastatic melanoma is directly related to the increased use of ICIs, which are often called immunotherapy. Drugs have improved survival in melanomas with and without BRAF mutations.

The term “immune checkpoint inhibitor” comes from the mechanism of action of the drugs. The human immune system, the body’s natural defenses against disease, has a series of checks and balances (checkpoints) that allow the system to protect the body but also reject or suppress the system so that it does not destroy normal cells and tissues. Skin cancer and other types of cancer have the ability to “rein in” indefinitely. ICIs block the melanoma-suppressing effect, allowing the immune system to respond more aggressively to cancer.

Two types of ICIs are available to treat skin cancer: the PD-1 inhibitor pembrolizumab (Keytruda) and nivolumab (Opdivo) and the CTLA-4 inhibitor ipilimumab (Yervoy). PD-1 and CTLA-4 indicate specific immune system checkpoints where drugs focus their anticancer activity.

Pembrolizumab and nivolumab are widely used as the initial treatment for advanced melanoma. Nivolumab is also approved for use with ipilimumab. Ipilimumab can be used alone but is often used in combination with nivolumab. Patients who respond to ICIs often have prolonged responses – much longer than chemotherapy or targeted therapies.

injection therapy

Sometimes, a doctor may inject cancer medicine directly into the melanoma, a treatment called intralesional therapy. This type of treatment is usually used to shrink a tumor before surgery or to relieve symptoms. A drug called T-VEC (Imlygic) is approved for direct injection.

Clinical trials

Although newer treatments have improved survival and quality of life in melanoma, many patients do not benefit from treatment, or the benefits are short-lived. Enrolling in a clinical trial gives patients access to treatments that may provide better results.

Several planned and ongoing trials are evaluating drug combinations, as well as new and innovative approaches to treatment. Ask your doctor if a clinical trial is the best option for you.

Read previous installments in this series:

For your patients: What is skin cancer?

To Your Patients: Is What You See Harmless, or Is It Skin Cancer?

For Your Patients: Is It Skin Cancer or Something Else?

For your patients: What do you know about treating skin cancer in its early stages?

Medical Journeys is a collection of clinician-reviewed clinical resources intended for physicians and other healthcare professionals in addition to the patients they serve. Each episode of this 12-part journey through a medical condition contains a physician’s guide and a downloadable/printable resource for patients. Medical Journeys chart every step of the way for doctors and patients and provide resources and ongoing support, as the team of caregivers navigate the disease course.

  • Charles Bankhead Senior Editor in the Department of Oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage today in 2007. Follow