Immunotherapy combo could overcome melanoma anti-PD-1 resistance

Use of the immune checkpoint inhibitor immunotherapy drug ipilimumab plus nivolumab has been shown to be effective as second-line therapy in metastatic melanoma that is resistant to PD-1 inhibitors.

In a Phase II clinical trial, the anti-cancer treatment extended progression-free survival (PFS) by 37 percent compared to participants who received ipilimumab alone.

Treating melanoma with ipilimumab and nivolumab

This approach facilitated greater overall treatment response rate compared to those who received the current standard therapy of ipilimumab alone.

Results from the trial, published in Nature Medicine, are “practice-changing” declared Dr Antoni Ribas, the study’s senior author, a professor of medicine at the David Geffen School of Medicine at UCLA and Director of the UCLA Health Jonsson Comprehensive Cancer Center’s Tumor Immunology Program.

Nivolumab blocks an immune checkpoint protein on T cells called PD-1. Ipilimumab inhibits the protein CTLA-4. These inhibitors can help restore the natural ability of T cells to attack cancer cells.

Prior to this study for melanoma, it has been unclear whether patients with PD-1 inhibitor-resistant cancers can continue the PD-1 agent in combination with a CTLA-4 inhibitor or should be switched to a CTLA-4 inhibitor only.

“The combination had the potential to better activate the immune system against cancer by simultaneously blocking two main immune checkpoints, increase the immune infiltration in the cancer and thereby overcome resistance to anti-PD-1 alone,” stated Dr Ribas.

Based on the trial results, the combination approach “should be the preferred drug regime for people with cancer that has not responded to prior immunotherapy treatment,” Dr Ribas added.

Over half of metastatic melanoma tumours are resistant to PD-1 inhibitors, according to the researchers. When resistance occurs, patients are often switched to CTLA-4 inhibitors.

Results from the immunotherapy drug combination trial

Of the 91 melanoma patients in the clinical trial, sixty-eight patients were assigned to receive the combination of ipilimumab and nivolumab. There were 23 patients who were just given ipilimumab.

Results showed that patients given the combination treatment also had higher response rates. Twenty-eight percent of patients saw their tumour shrink. This was compared to only nine percent of patients only given ipilimumab. 

Overall, “approximately one third of the patients receiving the immunotherapy combination had improved outcomes,” Dr Ribas concluded.