Dr Luke on the Background of the KEYNOTE-716 Trial in High-Risk Melanoma

Jason Luke, MD, FACP, associate professor, medicine, Division of Hematology/Oncology, director, Cancer Immunotherapeutic Center, Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, discusses the background of the phase 3 KEYNOTE-716 trial (NCT03553836) of pembrolizumab (Keytruda) vs placebo as adjuvant therapy in patients with stage IIB or IIC melanoma, highlighting previous data from the trial that led to the 36-month follow-up report.

Luke and colleagues presented the final analysis of distant metastasis–free survival (DMFS) in the phase 3 study at the 2023 ASCO Annual Meeting. Patients treated with pembrolizumab had a 41% reduction in the risk of distant metastases when compared with patients who were treated with placebo (HR, 0.59; 95% CI, 0.44-0.79). Additionally, patients treated with pembrolizumab achieved a 36-month DMFS rate of 84.4% vs 74.7% in those who received placebo.

The KEYNOTE-716 trial is global, randomized, placebo-controlled clinical trial investigating the use of the anti-PD–1 immunotherapy pembrolizumab vs placebo in patients with high-risk melanoma, Luke begins. This trial was game changing for the melanoma treatment field, righting a wrong that has been present since the initial FDA approvals of adjuvant therapy in this disease, Luke shares. Although adjuvant immunotherapy reduces recurrence in stage IIIdisease, the risk of recurrence in patients with stage IIB or IIC melanoma is similar to that of patients with stage IIIB melanoma, Luke explains. The KEYNOTE-716 data support the use of adjuvant pembrolizumab in all patients with melanoma with similar levels of risk, Luke emphasizes.

The initial report of the phase 3 trial was read out at the 2021 ESMO Congress, where investigators reported that the study had met its primary end point of recurrence-free survival (RFS) at the 12-month protocol assessment, Luke expands. At 12 months, Luke says the investigators noticed an initial difference in RFS with pembrolizumab compared with placebo. Mature data are based on 36 months of follow-up and emphasize the increasinglydurable RFS and DMFS benefits with pembrolizumab vs placebo in patients with high-risk melanoma, Luke concludes.