Tara C. Mitchell, MD
Evidence continues to build for the long-term efficacy of PD-1–targeting immunotherapies in melanoma, including fresh data indicating when patients can stop taking the drugs and still maintain a response, according to Tara C. Mitchell, MD. The future will bring an increased focus on novel combinations and more informative biomarkers.
Reflecting on 2016 clinical findings and FDA approvals, MItchell said that pembrolizumab, nivolumab, the PD-L1 inhibitor atezolizumab (Tecentriq), the oncolytic virus talimogene laherparepvec (T-VEC; Imlygic), and the CTLA-4 inhibitor ipilimumab (Yervoy), have all demonstrated encouraging and durable responses, which have been confirmed with longer follow-up. The question is where the field will go next.
Single-Agent PD-1 Inhibitor Efficacy
Long-term follow-up from the phase I KEYNOTE- 001 trial, in which patients were randomly assigned to receive pembrolizumab or ipilimumab, demonstrated that those who received pembrolizumab had an improvement in survival versus those who had treatment with the CTLA-4 inhibitor.1
Additionally, Mitchell noted that patients enrolled on the initial pembrolizumab trial achieved a complete response (CR), with the majority of patients responding at the 9- or 12-week mark of their first imaging assessment. “In all of the patients except for 2, the response was ongoing after stopping pembrolizumab,” said Mitchell. “We now know we can stop PD-1 blockade after a confirmed CR. In this case, 97% of patients will have an ongoing CR that is durable after stopping therapy.“
Dual Checkpoint Therapy
Immunotherapy combination regimens for patients with melanoma were investigated as frontline treatment in the randomized, doubleblind, multicenter, phase III CheckMate-067 trial.2
Here, nivolumab and ipilimumab were explored as monotherapy and in combination in a 1:1:1 ratio in a total 945 patients. They were treated with nivolumab alone (n = 316), nivolumab plus ipilimumab followed by nivolumab alone (n = 314), or ipilimumab alone (n = 315), with the co-primary endpoints being progression-free survival (PFS) and OS.
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