Advanced Skin Cancer Responds Well To Combination With Immunotherapy

For patients that are diagnosed in the late stages of skin cancer, treatment with a combination of targeted treatments with immunotherapy is ideal.

Highlights

Melanoma is the deadliest form of skin cancer, most of which have a BRAF mutation.
The study looked at the most effective treatment for patients diagnosed with advanced BRAF-mutated melanoma but not yet received any treatment.
Targeted therapy with chemotherapy drugs was effective in improving progression-free survival.
Immunotherapy was associated with lowest risk of life-threatening events.

Patients that are diagnosed in the late stages of one of the most common and deadly forms of skin cancer, melanoma, treatment with a combination of immunotherapy options improves survival and lowers the risk of life-threatening events.

Cutaneous melanoma is an aggressive and deadly form of skin cancer.

Melanoma - Causes, Symptoms, Diagnosis, Treatment & Prevention
Melanoma of the skin is a dangerous type of skin cancer that usually appears as a cancerous mole due to exposure to the sun’s damaging UV rays.

‘Combination of targeted therapies and immunotherapy options improves survival and lowers the risk of life-threatening events.’

According to the Canadian Cancer Society, the disease accounts for 3.3% of new cancer cases each year in Canada, and it has a 15% death rate.

In its early stages, melanoma is often cured with surgery alone, however most patients who are diagnosed in the late stages of disease are not candidates for surgery and drug therapy is the main course of treatment.

The study was conducted by researchers from the McMaster University and published in JAMA Oncology.

New Treatment Resistant Mechanism Identified In BRAF Mutant Melanoma
Inactivation of tumor suppressors STAG2 or STAG3 reactivates cell-growth signaling pathway in BRAF mutant melanoma.

"This is the first analysis to draw comparison between targeted and immune therapies for BRAF-mutated melanomas," said Feng Xie, principal investigator of the study, who is an associate professor in the Department of Clinical Epidemiology and Biostatistics at McMaster's Michael G. DeGroote School of Medicine.

"Our results will help patients and clinicians choose treatments." Xie added.

Ipilimumab Combined With Local Treatments Improve Survival for Melanoma Patients
Local peripheral treatments are not used to cure patients with malignant melanoma; rather, they are used to provide relief from symptoms caused by the melanoma.

Tahira Devji, the first author of the paper and a PhD student of McMaster's Health Research Methodology Program, said that around 40 to 60 per cent of melanomas have a mutation in the BRAF protein.

A number of effective treatment options are available for patients with advanced BRAF-mutated melanoma, which fall under two classes of drug therapies:

targeted therapy, like chemotherapy, which stops cancer from growing and spreading
immunotherapy, which works by stimulating the immune system to attack tumor cells.

It has been unclear which is the optimal initial treatment.

N-Acetyl Cysteine Improves Effectiveness for Melanoma
Culturing T cells in N-acetyl cysteine (NAC) before they are infused as immunotherapy improves effectiveness and outcomes in a preclinical model of melanoma.

The goal of the study was to estimate the relative efficacy and safety of systemic therapies for those who have been diagnosed with advanced BRAF-mutated melanoma but not yet received any treatment.

The team evaluated 15 randomized controlled trials published between 2011 and 2015, assessing the benefits and harms of targeted or immune checkpoint inhibitors in 6,662 patients with cancer that had spread to the lymph nodes and surgery was not an option, or distant metastatic melanoma.

They found that combined BRAF and MEK targeted therapy and PD-1 immunotherapy were both equally effective in improving overall survival.

Combined BRAF and MEK inhibition was most effective in improving progression-free survival.

PD-1 inhibition was associated with the lowest risk of life-threatening events.

PD-1 is a checkpoint protein on immune cells called T cells.

It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body. It does this when it attaches to PD-L1, a protein on some normal (and cancer) cells.

When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them evade immune attack.

Monoclonal antibodies that target either PD-1 or PD-L1 can boost the immune response against cancer cells and have shown a great deal of promise in treating certain cancers.

"While the data in our study represents best available evidence, using more than one kind of immunotherapy shows promise in early outcomes in clinical trials and could change the treatment landscape once longer-term results are published," said Feng Xie.

They concluded that the safety of PD-1 inhibitors supports using this treatment option as first-line therapy in circumstances where quick action is not a priority.

References

Immune checkpoint inhibitors to treat cancer - (http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/cancer-immunotherapy-immune-checkpoint-inhibitors)

Source-Medindia