A review on new therapies to treat metastatic melanoma

This study reviewed other studies about different treatments for metastatic (spread to other parts of the body) melanoma. Researchers suggested that targeted therapy improves overall survival of these patients when compared to chemotherapy.

Melanoma is the most dangerous common skin cancer. 70 to 80% of patients are detected with early stage melanoma which can be treated with surgery. When melanoma is detected at a later stage there is a risk of cancer spreading to other parts of the body. In this case chemotherapy alone and chemotherapy combined with other drugs (biochemotherapy) are the standard treatments. However, only a few people experience tumor shrinkage and less then 10% can be cured after 5 years.

Over the past few years, new drugs have been used with improved results. However, the survival advantage of these treatments over older treatments is not fully clear.  

This review compared the treatment results of patients treated with older therapies (chemotherapy alone or biochemotherapy) and newer drugs such as immune therapies (anti-CTLA4 and anti-PD1 inhibitors), targeted drugs (BRAF and MEK inhibitors) and anti-angiogenic drugs.  

This study reviewed 122 other studies and included information about 28,561 metastatic melanoma patients.

When compared to single agent chemotherapy, a combination of different chemotherapy drugs did not improved survival. These patients also had a 97% higher risk of increased toxicity (negative side effects).

Patients who received biochemotherapy (chemotherapy combined with interferon-alpha or interleukine-2) had a 10% improvement in the odds of a better progression-free survival (PFS; time from treatment to cancer progression) when compared to chemotherapy alone. However, these patients had a 35% higher risk of toxicity.

Patients treated with the immune therapy (helps the immune system to attack and kill cancer cells) anti-CTLA-4 in combination with chemotherapy had a 24% improvement in the odds of a better PFS when compared to chemotherapy alone. However, patients treated with the combination had a 69% higher risk of toxicity. Furthermore, patients treated with anti-PD1 agents had a 58% improvement in the odds of a better overall survival (time from treatment until death from any cause) and 51% in the odds of a better PFS. Anti-PD1 agents were also associated with 45% lower risk of increased toxicity when compared to chemotherapy alone.

The combination of anti-CTLA4 and anti-PD1 was associated with better PFS with no significant changes in toxicity.

Treatment with BRAF inhibitors (in patients with BRAF-mutated melanoma) was associated with a 60% improvement in the odds of a better overall survival and 73% in the odds of a better PFS compared to chemotherapy. Also, no differences were seen in terms of toxicity.

Compared to chemotherapy MEK inhibitors did not improve overall survival. However, they were associated with a 42% improvement in the odds of a better PFS and an increased risk (61%) of a higher toxicity.

Compared to BRAF inhibitors alone, the combination of BRAF and MEK agents was associated with a 30% improvement in the odds of a better survival and 44% in the odds of a better PFS, without changes in toxicity.

Anti-angiogenic drugs reduce blood supply to cancer cells, inhibiting their growth. When combined with chemotherapy, patients had a 40% improvement in the odds of a better overall survival and 31% in the odds of a better PFS. No significant changes in toxicity were associated with this treatment.

This review suggested that many treatments offer improved cancer response and outcomes when compared to chemotherapy, especially BRAF and MEK inhibitors (used to treat BRAF-mutated melanomas).