Neoadjuvant Combination Checkpoint Inhibition May Be Feasible for Stage III Melanoma
Future studies on checkpoint inhibition in melanoma must evaluate ways of reducing toxicity.
Neoadjuvant treatment of stage III melanoma using combination immunotherapy with ipilimumab plus nivolumab was determined to be feasible, but resulted in high toxicity rates in a small study.1 Based on these results, further investigation into combination neoadjuvant immunotherapy in this patient group should investigate ways to reduce toxicity, according to study researchers.
Preclinical research has suggested that neoadjuvant immunotherapy could be superior to adjuvant therapy, authors of the study, published in Nature Medicine, recently wrote. Additionally, neoadjuvant therapy could have several advantages, such as to determine its efficacy in a patient for the prediction of the drug's potential future efficacy as an adjuvant therapy in that same patient, or to reduce tumor burden prior to surgery.
Here, the researchers enrolled 20 patients with stage III melanoma and randomly assigned them to to ipilimumab 3 mg/kg plus nivolimumab 1 mg/kg as either adjuvant or neoadjuvant therapy.
Overall, use of neoadjuvant therapy was feasible; there were no delays in surgical resection among patients assigned to this group.
In the neoadjuvant arm, 9 of 10 patients were evaluated for response and 78% achieved profound pathological response, include 3 complete responses. The researchers noted that none of the patients that responded have relapsed thus far, at a median follow-up of 21.6 months after surgery, making pathological response “a promising marker for neoadjuvant immunotherapy evaluation.”
In both arms, 9 out of 10 patients experienced 1 or more grade 3/4 adverse events. No previously undescribed adverse events occurred.
- Blank CU, Rozeman EA, Fanchi LF, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma [published online October 8, 2018]. Nature Med. doi: 10.1038/s41591-0198-0