Randomized Phase II Trial of Consolidation Pembrolizumab After Definitive Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma: KCSG HN19-09, CONPELAN Study.

Abstract

The benefit of consolidation programmed cell death protein 1 (PD-1) blockade after chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. Patients with stages II-IVB NPC were randomized (2:1) to pembrolizumab 200 mg or placebo every 3 weeks for up to 17 cycles after chemoradiotherapy. The primary endpoint was 3-year progression-free survival (PFS). Fifty-three patients were randomized (pembrolizumab, n = 34; placebo, n = 19). The 3-year PFS rates were 56.5% and 57.8% in the pembrolizumab and placebo arms, respectively (one-sided p = 0.142; stratified HR, 0.408). Grade 3 or higher adverse events occurred only in the pembrolizumab arm (8.8%). In an exploratory analysis (n = 40), high intratumoral TIL density was associated with reduced recurrence in the pembrolizumab arm (OR, 0.04; p = 0.010) but not the placebo arm. Consolidation pembrolizumab did not improve PFS in unselected locally advanced NPC. Exploratory immune profiling suggested a predictive signal warranting prospective validation.