Georgina V. Long, MD, PhD, on Resected Melanoma: Biomarkers for and Efficacy of Adjuvant Nivolumab vs Placebo

Georgina V. Long: Resected Stage 2B and 2C melanoma has a very poor prognosis. In fact, at five years, patients with stage 2C melanoma have a 45% risk of recurrence. And for stage 2B melanoma, 35% risk of recurrence. The survival of this group of patients is worse than that of stage 3A melanoma and the survival of stage 2C melanoma is equivalent to the survival of stage 3B melanoma. This is a poor prognostic group. Checkmate 76K explored adjuvant nivolumab versus placebo in resected stage 2B and 2C melanoma in patients who had undergone a wide local excision and a sentinel node biopsy, which was negative. 790 patients were randomized two to one to nivolumab versus placebo. We've already seen the relapse-free survival primary analysis last year, and there was a 58% reduction in the risk of recurrence with adjuvant nivolumab. We are now presenting the exploratory biomarker analysis from this trial. So baseline, primary melanoma tissue, and baseline CRP, serum CRP was correlated with outcome within each arm and versus each arm. And what we found was that for every biomarker subgroup, nivolumab improved the relapse-free survival over placebo. And this included tumor mutation burden, interferon gamma, PD-L1 expression at baseline, CD8 infiltration at baseline, the CRP. So when we compared the prognostic biomarkers overall in the trial, we found that the two factors that were most important for prognosis, so predicting recurrence in the total trial population, that was the CRP and the stage. However, when we did our multivariate model to look at what was predictive of best outcome with adjuvant nivolumab over placebo, we found that the baseline biomarkers that were predictive or most predictive were the interferon gamma at baseline and the tumor mutation burden. Our next steps are to make a multifactorial model, which includes both clinical and tissue biomarkers to predict outcome of patients with resected 2B and 2C melanoma treated with adjuvant nivolumab.