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

Eva Ellebaek, Shawez Khan, Lars Bastholt, Henrik Schmidt, Charlotte Aaquist Haslund, Marco Donia*, Inge Marie Svane

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

24 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number113476
JournalEuropean Journal of Cancer
Volume198
Number of pages8
ISSN0959-8049
DOIs
Publication statusPublished - Feb 2024

Keywords

  • Anti-CTLA-4
  • Anti-PD-1
  • Immunotherapy
  • Metastatic melanoma
  • PD-L1 status
  • Melanoma/pathology
  • B7-H1 Antigen
  • Humans
  • Ipilimumab/therapeutic use
  • Combined Modality Therapy
  • Nivolumab/therapeutic use

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this