Details

Autor(en) / Beteiligte

• Kreft, Sophia
• Gesierich, Anja
• Eigentler, Thomas
• Franklin, Cindy
• Valpione, Sara
• Ugurel, Selma
• Utikal, Jochen
• Haferkamp, Sebastian
• Blank, Christian
• Larkin, James
• Garbe, Claus
• Schadendorf, Dirk
• Lorigan, Paul
• Schilling, Bastian

Titel

Efficacy of PD-1–based immunotherapy after radiologic progression on targeted therapy in stage IV melanoma

Ist Teil von

• European journal of cancer (1990), 2019-07, Vol.116, p.207-215

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Targeted therapy (TT) is an effective treatment for advanced BRAFV600-mutated melanoma, but most patients eventually acquire resistance and progress. Here, we evaluated the outcome of second-line immune checkpoint blockade (ICB) after progression on dual BRAF and MEK inhibition. Patients with metastatic melanoma progressing on combined BRAF + MEK inhibition and receiving second-line ICB between 2015 and 2019 in 9 tertiary referral centres were enrolled. Demographic and clinical data and blood counts of all patients were collected retrospectively. We identified 99 patients with stage IV melanoma receiving ICB (nivolumab, pembrolizumab [n = 39] or ipilimumab plus nivolumab [n = 60]) after progression on combined TT. The median progression-free survival was similar in the PD-1 and ipilimumab plus nivolumab group (2.6 months [95% confidence interval {CI}, 2.0–3.1] vs. 2.0 [95% CI, 1.4–2.6], p = 0.15). The objective response rate was 18.0% in the PD-1 and 15.0% in the ipilimumab plus nivolumab group (p = 0.70). The disease control rate was 25.7% for monotherapy and 18.3% for combined ICB (p = 0.39). The median overall survival was 8.4 months (95% CI, 5.1–11.7) for patients receiving PD-1 monotherapy and 7.2 months (95% CI, 5.2–9.1) for patients receiving ipilimumab plus nivolumab (p = 0.86). The latter was associated with a higher rate of treatment-related adverse events (AEs). No significant association of laboratory values or clinicopathological characteristics with response to second-line ICB was observed. PD-1 monotherapy and combined ipilimumab plus nivolumab show similar activity and outcome in patients with melanoma resistant to BRAF + MEK inhibition. However, combined ipilimumab plus nivolumab was associated with a higher rate of treatment-related AEs compared with monotherapy. •After progression on targeted therapy, outcome of immune checkpoint blockade (ICB) is poor.•Response rates were similar for PD-1 plus CTLA-4 and PD-1 monotherapy.•Overall survival after ICB was similar in both groups.•Dual ICB was associated with a higher rate of immune-related adverse events.