PD-L1 is a biomarker of real-world clinical outcomes for anti-CTLA-4 plus anti-PD-1 or anti-PD-1 monotherapy in metastatic melanoma

Background: Metastatic melanoma (MM) is commonly treated with a combination of nivolumab and ipilimumab, regardless of tumor PD -L1 expression. Methods: We conducted a population -based study including all patients with MM (except ocular melanoma) treated in Denmark with first -line combination therapy or anti -PD -1 monotherapy since January 2017. Baseline data including known prognostic characteristics were used in multivariable and propensity -matched score (PMS) analyses to assess progression -free survival (PFS), melanoma -specific survival (MSS), and overall survival (OS) according to PD -L1 expression. Results: We identified 1341 eligible patients, with known PD -L1 status for 1081 patients (43% PD -L1 >= 1%, 57% PD -L1 < 1%). PD -L1 >= 1% was an independent positive prognostic biomarker for survival in the overall cohort (MSS: HR 0.66, CI 0.52-0.83, p < 0.001). In the PMS PD -L1 >= 1% cohort, combination therapy showed similar clinical outcomes to monotherapy (PFS: HR 1.41, CI 0.94-2.11, p = 0.101; MSS: HR 1.21, CI 0.70-2.11, p = 0.49; OS: HR 1.17, CI 0.68-2.00, p = 0.567). In contrast, in the PMS PD -L1 < 1% and in the PMS PD -L1 < 1% BRAF WT cohorts, combination therapy improved PFS (respectively with HR 0.70, CI 0.53-0.93, p = 0.013; and HR 0.54, CI 0.37-0.78, p = 0.001), but did not reach statistically significant improvements of MSS (HR 0.72, CI 0.50-1.02, p = 0.065; and HR 0.79, CI 0.51-1.21, p = 0.278) or OS (HR 0.78, CI 0.56-1.08, p = 0.135; and HR 0.81, CI 0.54-1.21, p = 0.305) compared to monotherapy. Conclusion: Our findings support previous exploratory analyses of Checkmate -067, highlighting that improved clinical outcomes with combination therapy are not established in unselected patients with high (>= 1%) tumor PD -L1 expression.