Melanoma

Melanoma

Melanoma is by far the most serious form of skin cancer. For all stages of melanoma combined, five-year survival has increased from 82 percent in the late 1970s to 93 percent in recent years.

Melanoma research has been a pioneer in immunotherapy, using drugs to trigger the body's immune defenses to fight melanoma tumors. In 2010, researchers showed for the first time that a drug targeting the immune system can improve survival among people with advanced melanoma. The following year, a second drug targeting a genetic abnormality in some melanomas achieved a similar result. While investigators continue to study why these treatments don't work in all patients, or yet cure the disease, they signal that progress against melanoma is gaining speed and that therapy will become increasingly personalized in the years ahead.

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2015

Adjuvant ipilimumab lowers recurrence risk for earlier-stage melanoma

Adjuvant ipilimumab lowers recurrence risk for earlier-stage melanoma

A large clinical trial finds that the immunotherapy ipilimumab (Yervoy), when given after surgery, lowers the risk of cancer recurrence and extends survival for patients with stage III melanoma who have a high risk for recurrence. This marks the first study to show the effectiveness of ipilimumab against earlier-stage melanoma (ipilimumab was first approved in 2011 for advanced melanoma). Ipilimumab attaches to a protein on cancer-killing T cells called CTLA-4, which acts as a brake on the immune system. This unleashes the immune system to attack the cancer. 

2014

First targeted therapy combination approved for high-risk melanoma

First targeted therapy combination approved for high-risk melanoma

FDA grants accelerated approval for combined modality therapy with trametinib (Mekinist) and dabrafenib (Tafinlar) in patients with advanced or inoperable melanoma that harbor certain BRAF gene mutations. The approval is based on studies demonstrating that the new regimen leads to long-lasting responses in most patients. The two drugs target different molecules in a pathway involved in melanoma growth. 

FDA approves two immunotherapies for melanoma

FDA approves two immunotherapies for melanoma

FDA grants accelerated approval to pembrolizumab (Keytruda) and nivolumab (Opdivo) for patients with advanced melanoma that cannot be removed with surgery who no longer respond to other treatments.

These therapies, known as “immune checkpoint inhibitors,” work by blocking a pathway called PD-1, that prevents the body’s immune system from attacking cancer cells.

Approval comes following research showing that the therapies shrank tumors in up to 40% of patients. In one clinical trial, nivolumab extended survival compared to targeted therapy for patients with BRAF mutations. 

2011

Second targeted drug extends survival for advanced melanoma

Second targeted drug extends survival for advanced melanoma

The FDA approves the targeted drug vemurafenib (Zelboraf), based on data showing the drug shrinks tumors and improves survival in advanced melanoma patients whose tumors have a specific mutation in a gene known as BRAF. In many cases, patients experience dramatic reductions in pain and tumor shrinkage within days of starting this therapy. However, research is ongoing to determine why the cancer typically stops responding to this novel drug after several months.

2010

New prohibitions on indoor tanning after it’s declared carcinogenic

New prohibitions on indoor tanning after it’s declared carcinogenic

2009-2017

In 2009, the International Agency for Research on Cancer, a working group of the World Health Organization, declared that UV-emitting tanning devices are “carcinogenic to humans.”

Between 2011 and 2017, several new pieces of legislation are enacted to restrict the use of indoor tanning, starting with a new California law prohibiting indoor tanning to people under the age of 18. Fourteen other states and the District of Columbia subsequently follow suit.  In 2014, the U.S. Food & Drug Administration issues an order requiring all indoor tanning devices to carry a visible black-box warning against use before age 18, and it reclassifies indoor tanning devices from a low to a moderate risk, allowing the agency greater control over the devices. Policy changes continue in Australia, where nearly all states enact bans on indoor tanning in 2015.

First drug shown to improve survival for patients with advanced melanoma

First drug shown to improve survival for patients with advanced melanoma

In a Phase III study, the targeted drug ipilimumab (Yervoy) – which boosts a specific component of the immune system – is found to improve survival and delay disease progression in patients whose advanced melanoma progresses despite other therapies. The drug is approved for this use in early 2011.

Soon after, a second trial finds that treatment using a combination of ipilimumab and dacarbazine (a chemotherapy drug commonly used in melanoma) extends survival compared to dacarbazine treatment alone.

2009

Researchers begin mapping the melanoma genome
Melanoma incidence continues to rise in the U.S.

Melanoma incidence continues to rise in the U.S.

A review of U.S. National Cancer Institute data shows that the annual number of new cases of melanoma increased 45 percent among non-Hispanic whites between 1992 and 2004 – rising 3.1 percent per year. At the same time, the overall melanoma death rate (the number of melanoma deaths per 100,000 people) rose 0.4 percent annually. By 2015, the estimated lifetime risk for developing cutaneous melanoma will be 1 in 50. Melanoma incidence has increased at a faster pace than any other cancer in the last 50 years, heightening the need for continued research on effective melanoma prevention strategies and treatments.

2008

Microscopic examination improves accuracy of skin cancer screening

Microscopic examination improves accuracy of skin cancer screening

A review of published studies finds that a procedure called dermoscopy – involving direct, microscopic examination of moles and skin lesions – is more accurate than a doctor's visual examination for identifying potential melanomas on the surface of the skin. The review emphasizes the importance of using dermoscopy, which has been available since the 1990s, to ensure that more cancers are detected at an early stage when they are most responsive to treatment.

2005

Melanoma, other skin cancers increasing in young people

2002

Genetic "fingerprints" of melanoma tumors differ widely

Genetic "fingerprints" of melanoma tumors differ widely

Researchers learn that melanomas occurring in areas of the body not exposed to the sun (like the soles of the feet) may be genetically different than those arising in sun-exposed areas. They find many melanomas on skin without chronic sun exposure have mutations in genes known as BRAF or N-RAS, while melanomas in areas with consistent sun exposure are more likely to instead overproduce copies of the CKIT, CDK4 and CCND1 "oncogenes" (genes involved in cancer cell growth and replication). These findings help inform future research on drugs to target these individual genetic pathways. In 2010 and 2011, a new drug targeting the BRAF mutation is shown to substantially extend survival for melanoma patients with a specific BRAF gene mutation.

2001

New staging system helps doctors determine prognosis, select best melanoma treatments

New staging system helps doctors determine prognosis, select best melanoma treatments

The American Joint Committee on Cancer issues a major update to the system used by doctors to assess, or "stage," cases of melanoma. This new approach helps doctors more accurately identify those patients who are at high risk of developing advanced disease, determine the most appropriate therapy, compare treatment results with established standards and offer more reliable prognoses to patients. The system is updated again in 2010, to incorporate an increased understanding of the biology of melanoma and its treatment.

1998

Second immunotherapy drug approved for melanoma

1996

Interferon approved as first adjuvant treatment

Interferon approved as first adjuvant treatment

Interferon alpha 2b becomes available for patients who have a high risk of melanoma recurrence after their tumors are surgically removed. The FDA approves the immunotherapy treatment based on studies showing that one year of high-dose interferon therapy reduces the risk of melanoma recurrence and modestly improves overall survival. However, physicians still recommend it cautiously, due to its lengthy course of treatment and significant side effects, such as depression and flu-like symptoms.

1992

Sentinel lymph node biopsy introduced to assess the spread of melanoma to nearby lymph nodes

Sentinel lymph node biopsy introduced to assess the spread of melanoma to nearby lymph nodes

A surgical technique called sentinel lymph node biopsy becomes a less invasive way to assess whether early-stage melanoma has spread to surrounding lymph nodes. The procedure involves surgically removing the lymph node(s) that receives lymph drainage from the primary tumor – the "sentinel" node – and then examining it under a microscope for evidence of cancer. If the sentinel node is cancer-free, no further lymph nodes are removed and the patient is spared the previous practice of removing multiple lymph nodes. This more conservative approach is easier on patients and reduces the risk of post-operative side effects such as lymphedema. Later studies show that results of sentinel lymph node biopsy are one of the most important predictors of risk for melanoma recurrence. This information helps doctors determine which patients should be treated more aggressively to prevent their cancer from returning.

1987

Personalized immunotherapy can shrink some melanoma tumors

Personalized immunotherapy can shrink some melanoma tumors

Scientists first develop an experimental procedure called adoptive cell transfer, in which one or more of the patient's tumors are removed and specific anti-tumor white blood cells (called tumor infiltrating lymphocytes) are extracted. These cells are then grown in a laboratory to boost their ability to fight the cancer and returned to the patient, often in combination with chemotherapy. Remarkably, this personalized immunotherapy approach has been shown to shrink melanoma tumors in about half of patients whose tumor infiltrating lymphocytes are successfully treated in the laboratory. In part because of the complexity of the approach, the procedure is only available in a few centers worldwide, and research remains active to determine its appropriate role in treatment.

1984

Less extensive surgery found effective for removing melanoma tumors

Less extensive surgery found effective for removing melanoma tumors

Instead of the traditional practice of surgically removing up to two inches of skin and tissue surrounding a melanoma tumor, clinical trials show that margins of three-quarters of an inch or less around the tumor are sufficient. This refinement makes recovery easier and helps reduce the cosmetic impact of surgery.

1982

Research links sun exposure to melanoma risk

Research links sun exposure to melanoma risk

A growing number of studies in this period suggest that sun exposure plays an important role in the development of some melanomas. Specifically, frequency and duration of exposure, as well as a history of severe sunburn, are found to be associated with a person's risk of the disease. In the 1980s, the public health community and advocacy groups such as the Skin Cancer Foundation begin cautioning the public about the potential risks of sun exposure.

1978

Hereditary syndrome linked to increased melanoma risk

Hereditary syndrome linked to increased melanoma risk

Researchers identify a hereditary syndrome called dysplastic nevus syndrome (also known as B-K mole syndrome or Familial Atypical Multiple Mole and Melanoma, or FAMMM, syndrome) that is associated with an approximately 50 percent risk of developing melanoma by age 50. Patients with the syndrome have an unusually large number of moles, which are often irregular in size and shape and have specific coloring and microscopic features. These individuals need more aggressive screening so cancers can be detected at an early stage.

1961

Innovative technique enables intensive chemotherapy without increased systemic side effects

Innovative technique enables intensive chemotherapy without increased systemic side effects

A new approach known as isolated limb perfusion is introduced to help doctors deliver higher-than-usual doses of chemotherapy to an arm or leg where melanoma tumors have spread, without increasing the risk that the drugs will harm other parts of the body. During this procedure, the doctor temporarily stops the flow of blood to and from the affected limb, essentially isolating it with a tourniquet from the rest of the body, and then intravenously administers and circulates chemotherapy through the affected limb with the help of a special machine. The approach is further refined in the 1990s with the introduction of isolated limb infusion, which cuts procedure time, requires fewer specialized medical personnel and is less costly. Investigations continue to try to find better treatments using this technique.

1957

Key component of future melanoma treatment is discovered

Key component of future melanoma treatment is discovered

Researchers identify interferons – proteins produced in immune cells that help fight viruses, bacteria, and other pathogens. Later, in the 1980s, researchers begin to demonstrate that a specific type of interferon – known as interferon alpha 2b – can help reduce melanoma recurrences after surgery by boosting the immune system to fight cancer. The drug has since become a treatment option for many patients with the disease, although physicians still recommend it cautiously, due it its lengthy course of treatment and significant side effects, such as depression and flu-like symptoms.