Investigators found that a combination of immunotherapy options improves survival and lowers the risk of life-threatening events. [NIH]
Investigators found that a combination of immunotherapy options improves survival and lowers the risk of life-threatening events. [NIH]

A vast array of cancer immunotherapy compounds has flooded the market in recent years, all tethered to the hope of significantly improving patient survival rates. While many patients have experienced improvements in disease states, there are those for whom immunotherapy provides little to no benefit. Many of these individuals contain a genetic background that is incompatible with the therapeutic compound, while others suffer from a form of cancer that has been intractable toward immunotherapy.

Now, a team of Canadian researchers from McMaster University in Ontario has found that for patients diagnosed in the late stages of one of the most common and deadly forms of skin cancer, treatment with a combination of immunotherapy options improves survival and lowers the risk of life-threatening events.

“This is the first analysis to draw comparison between targeted and immune therapies for BRAF-mutated melanomas,” explained senior study investigator Feng Xie, Ph.D., 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.”

Cutaneous melanoma is an aggressive and deadly form of skin cancer. In the U.S., melanoma accounts for approximately 1% of all skin cancer diagnoses, yet is the cause of the majority of skin cancer deaths. Moreover, 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 primary course of treatment.

Interestingly, between 40% and 60% of melanomas have a mutation in the BRAF gene, and while a number of effective treatment options are available for patients with advanced BRAF-mutated melanoma, it has been unclear which is the optimal initial treatment. The therapies typically fall into two classes of drug therapies: targeted therapy, like chemotherapy, which stops cancer from growing, and spreading and immunotherapy, which works by stimulating the immune system to attack tumor cells.

In this current study, the investigators set out 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 findings from this study were published recently in JAMA Oncology in an article entitled “Systemic Therapy for Previously Untreated Advanced BRAF-Mutated Melanoma.”

The team evaluated 15 randomized controlled trials published between 2011 and 2015, assessing the benefits and problems of targeted or immune checkpoint inhibitors in 6662 patients with cancer that had spread to the lymph nodes and in which surgery was not an option—called distant metastatic melanoma.

The Canadian team found that combined BRAF- and MEK-targeted therapy and programmed cell death 1 (PD-1) immunotherapy were both equally effective in improving overall survival. Combined BRAF and MEK inhibition was most effective in improving progression-free survival, whereas PD-1 inhibition was associated with the lowest risk of life-threatening events.

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

“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,” concluded Dr. Xie.








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