Pembrolizumab and ipilimumab are both so-called immune checkpoint inhibitors. In recent years it has become clear that the body’s own immune system can sometimes fight cancer. However, this immune response is often suppressed. Molecular checkpoints can prevent immune cells called T cells from attacking the cancer cells. Pembrolizumab and ipilimumab each block one such checkpoint, respectively the cell receptor PD-1 and the protein CTLA4. This causes the T cells to become active and fight the tumor.
Ipilimumab was approved by the American Food and Drug Administration as a treatment against advanced melanoma in 2011. It has improved survival for these patients, for whom until recently no treatment was available. But it isn’t effective in all patients. In a large, international study coordinated by the pharmaceutical company Merck Sharpe & Dohme, treatment with ipilimumab is now compared with treatment with the recently approved drug pembrolizumab. A total of 834 patients in seventeen treatment centers worldwide were randomly divided into three groups. The first two groups received a 10mg/kg dose of pembrulizumab every two or three weeks; the third group received 4 doses of ipilimumab 3mg/kg every three weeks.
The six month progression free survival rate in both patient groups who received pembrolizumab was almost double compared to the rate in the ipilimumab group (46-47 % versus 26,5%). The twelve month survival rate was also higher in the pembrolizumab groups: 74,1% (two week regime) and 68,4% (three week regime) versus 58,2% in the ipilimumab group. On top of that, patients who received pembrolizumab experienced less side effects. Side effects of immunotherapy typically include diarrhea, skin rashes and itching.
New standard immunotherapy
Cancer researcher and physician dr. Christian Blank was the principal investigator for this study within the Netherlands Cancer Institute. He has been researching PD-1 since 2001. Blank comments: “This landmark trial compares for the first time the anti-PD-1 antibody pembrolizumab with the current standard immunotherapy for melanoma, ipilimumab. I am very proud to see our efforts in preclinical research focusing on PD-1 leading to this improvement for melanoma patients.” Pembrolizumab is now the new standard immunotherapy for melanoma patients, and is available for patients in the fourteen Dutch melanoma centers.
Netherlands Cancer Institute (NKI)