Does early use of high-dose glucocorticoids affect survival in patients with advanced melanoma treated with anti-PD-1 therapy?

This study evaluated the use of high-dose glucocorticoids (GCs) and their impact on the survival outcomes during anti-PD-1 therapy for the treatment of patients with advanced melanoma. The data showed that early high-dose GC use was associated with poorer outcomes after the onset of immune-related side effects.

Melanoma is an aggressive type of skin cancer. It has a high tendency to spread to other parts of the body (metastasis). The standard treatment for advanced melanoma is a combination of immunotherapy, chemotherapy, surgical removal of tumors, and radiation therapy.

Immunotherapy uses the body’s own immune system to fight cancer. PD-1 is a protein that can be found in high numbers on cancer cells. It can stop the immune system from killing cancerous cells. Pembrolizumab (Keytruda) is an example of PD-1 inhibitor. By blocking this protein it activates the immune system to attack tumor cells and kill them. Immunotherapy has been found to be effective in advanced melanoma.

The most common side effects associated with immunotherapy are immune-related. These often include skin rashes or inflammation in areas such as the lungs, intestines, or thyroid. Severe immune-related side effects often require immunosuppressive treatment with GCs. GCs are drugs that stop inflammation by suppressing the immune system. However, the use of high-dose GCs for the management of immune-related side effects and their impact on the survival outcomes during anti-PD-1 therapy remains unclear.

This study involved 947 patients with advanced melanoma. All patients were treated with anti-PD-1 therapy. The average follow-up time was 206 weeks. 54% (509) of the patients experienced immune-related side effects. 32% of patients received GCs in different doses to treat immune-related side effects. Patients were divided into 2 groups. Group 1 included 90 patients who were treated at the Massachusetts General Hospital. Group 2 included 419 patients who were treated at 4 different institutions in the US.

For group 1, the average survival without cancer worsening was 8 weeks with early high-dose GC use compared to 90 weeks without early high-dose GC use. High-dose GC was considered a dose of 60mg prednisone (Deltasone) or higher. For these patients, early-onset immune-related side effects with high-dose GC use were associated with a 5.37 times higher risk of a poorer survival without cancer worsening than without early-high-dose GC use.

For group 1, the average overall survival was 48 weeks with high-dose GC use compared to not reached (exceeded the average follow-up period) without high-dose GC use. For these patients, early-onset immune-related side effects with high-dose GC use were associated with a 5.95 times higher risk of a poorer overall survival.

For group 2, the average survival without cancer worsening was 38 weeks with early high-dose GC use compared to 114 weeks without early high-dose GC use. For these patients in group 2, early-onset immune-related side effects with high-dose GC use were associated with a 1.69 times higher risk of a poorer survival without cancer worsening.

For group 2, the average overall survival was 126 weeks with high-dose GC use compared to 289 weeks without high-dose GC use. For these patients, early-onset immune-related side effects with high-dose GC use were associated with a 1.97 times higher risk of a poorer overall survival.

This study concluded that early high-dose GC use was associated with poorer outcomes after the onset of immune-related side effects. The authors recommend prudent use of GC early during anti-PD-1 therapy.

This study looked back in time at medical records. Future studies are necessary to validate the conclusions.