Ari VanderWalde, MD, MPH
Researchers have discovered that the combination of the CTLA-4 inhibitor ipilimumab and the PD-1 inhibitor nivolumab may be an effective second-line therapy in patients with PD-1 blockade–refractory metastatic melanoma, according to a recent study conducted by the SWOG Cancer Research Network and published by Ari VanderWalde, MD, MPH, an investigator with West Cancer Center and Research Institute in Germantown, Tennessee, and first author of the study and SWOG Study Chair, in Nature Medicine.1 These findings demonstrated the combination therapy may extend progression-free survival and may help patients overcome resistance to prior immunotherapies.
Study Methods and Results
In this multicenter clinical trial, the researchers enrolled 91 patients with refractory metastatic melanoma who had already been treated with a PD-1 inhibitor and had not received a CTLA-4 inhibitor. The researchers randomly assigned 68 patients to receive ipilimumab and nivolumab and 23 patients to receive ipilimumab alone. They then measured progression-free survival as the main endpoint and examined other factors such as the immune cells’ infiltration of the tumors, the cancer’s response to treatment, and any side effects the patients exhibited.
The researchers found that patients treated with the combination of ipilimumab and nivolumab demonstrated a 37% improvement in progression-free survival compared with those who received ipilimumab alone. Further, patients who received the combination of drugs experienced an overall response rate of 28% vs 9% among those who received ipilimumab monotherapy. The investigators found the side effects were similar to previous reports on this drug combination. The most frequent severe adverse event was diarrhea, and it occurred at the same rate in both groups.
“We found approximately one-third of the patients receiving the immunotherapy combination had improved outcomes,” said senior study author Antoni Ribas, MD, Professor of Medicine at the David Geffen School of Medicine and Director of the Tumor Immunology Program at the University of California, Los Angeles Jonsson Comprehensive Cancer Center. In a UCLA Health press release, Dr. Ribas concluded: “Sequencing immunotherapy treatments as was tested in this study is the next step forward in our efforts to better tailor the treatment options while limiting exposure to side effects. Patients with advanced melanoma can get an anti–PD-1 treatment upfront and only add the anti–CTLA-4 ipilimumab if they do not respond, so only the patients [who] need the combination are exposed to the increased toxicities.”
DISCLOSURE: The study was funded by grants from SWOG, National Institutes of Health, and the National Cancer Institute. For full disclosures of the study authors, visit nature.com.
1. VanderWalde A, Bellasea SL, Kendra KL, et al: Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: A randomized phase 2 trial. Nat Med. August 17, 2023 (early release online).