Adding Sargramostim to Ipilimumab Prolonged Survival in Metastatic Melanoma Trial

The gist: People with metastatic melanoma who are being treated with the drug ipilimumab (Yervoy) may live several months longer if they also take another drug called granulocyte-macrophage colony-stimulating factor (GM-CSF). In a recent clinical trial, researchers compared patients who took just ipilimumab with patients who took both ipilimumab and GM-CSF. Patients who took both lived several months longer. However, GM-CSF didn’t increase the amount of time that passed before cancer returned.

“The addition of sargramostim, a systemic granulocyte-macrophage colony-stimulating factor (GM-CSF), to the anti-CTLA-4 ipilimumab resulted in a significant improvement in overall survival in patients with metastatic melanoma when compared with treatment with ipilimumab alone, according to phase II study results published recently in JAMA: Dermatology. However, no difference in progression-free survival was found between the two study groups.

“ ‘The lack of correlation between overall survival and progression-free survival in this study presents challenges to clinical management and drug development because conventional radiographic criteria have not proven reliable for determining patient benefit,’ wrote researchers led by F. Stephen Hodi, MD, of the Dana-Farber Cancer Institute. ‘This introduces important considerations for the evaluation of treatment efficacy with particular immune therapies such as ipilimumab.’

“Previous research has shown therapeutic synergy between CTLA-4 blockade and GM-CSF secreting tumor cell vaccines. In addition, the combination of systemic GM-CSF with CTLA-4 blockade in patients with hormone-refractory prostate cancer resulted in clinical responses in more than half of patients with PSA declines.”

Immune Booster Combined with Checkpoint Blocker Improves Survival in Metastatic Melanoma

The gist: A treatment that combines the drug ipilimumab with a drug meant to boost the immune system has shown promise in a clinical trial with volunteer metastatic melanoma patients. In the trial, people who took the combo treatment survived about five months longer than people who took only ipilimumab. They also had fewer serious side effects.

“Patients with metastatic melanoma who were treated with ipilimumab, an immune checkpoint blocker, survived 50 percent longer – a median 17.5 months vs. 12.7 months – if they simultaneously received an immune stimulant, according to a study led by Dana-Farber Cancer Institute scientists.

“Patients in the clinical trial who got the combined therapies also had fewer serious adverse side effects than those who received only ipilimumab, the researchers report in the Journal of the American Medical Association.

“The group treated with both ipilimumab and the immune stimulant, called sargramostim, had a one-year survival rate of 68.9 percent vs. 52.9 percent in the ipilimumab-only group. In both groups, however, the median progression-free survival (the length of time before the cancer began to grow) was similar – 3.1 months…

“Larger trials and longer follow-up will be needed to confirm the results,’ he added. ‘But this opens the possibility of improving clinical outcomes and decreasing serious side effects in treating advanced melanoma with ipilimumab.’ ”