The invisible enemy.

Top Line: Patients with limited, resected metastatic melanoma had limited representation in the immune checkpoint inhibitor (ICI) clinical trials.

The Study: That’s because they often have no disease to measure. CheckMate-238 did include a subset of these patients who saw a doubling in progression-free survival, so nivolumab is a primary consideration for adjuvant therapy. But some consider observation until progression before starting immunotherapy. IMMUNED was a three-arm, randomized, phase 2 trial that focused only on stage IV melanoma with no measurable disease. Patients were randomized to ipilimumab + nivolumab, nivo alone, or placebo. The ipi + nivo arm was tough with nearly two-thirds of patients discontinuing treatment due to adverse events and a median time on treatment less than one-third that of the nivo and placebo arms. Nevertheless, ipi + nivo produced a significant improvement in 1- and 2-year recurrence free survival (RFS) of 75% and 70% compared to 52% and 42% with nivo alone and 32% and 14% with placebo. Likewise, median RFS went from 6 months with placebo to 12 months with nivo to not reached (at a median followup of 28 months) with ipi/nivo. 

TBL: Combo ipilimumab and nivolumab significantly improves recurrence-free survival for patients with stage IV melanoma, even when it’s been completely resected. | Zimmer, Lancet 2020