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

• Verfasst von: Kreft, Sophia [VerfasserIn]
• Verfasst von: Gesierich, Anja [VerfasserIn]
• Verfasst von: Eigentler, Thomas [VerfasserIn]
• Verfasst von: Franklin, Cindy [VerfasserIn]
• Verfasst von: Valpione, Sara [VerfasserIn]
• Verfasst von: Ugurel, Selma [VerfasserIn]
• Verfasst von: Utikal, Jochen [VerfasserIn]
• Verfasst von: Haferkamp, Sebastian [VerfasserIn]
• Verfasst von: Blank, Christian [VerfasserIn]
• Verfasst von: Larkin, James [VerfasserIn]
• Verfasst von: Garbe, Claus [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Verfasst von: Lorigan, Paul [VerfasserIn]
• Verfasst von: Schilling, Bastian [VerfasserIn]
• Titel: Efficacy of PD-1-based immunotherapy after radiologic progression on targeted therapy in stage IV melanoma
• Verf.angabe: Sophia Kreft, Anja Gesierich, Thomas Eigentler, Cindy Franklin, Sara Valpione, Selma Ugurel, Jochen Utikal, Sebastian Haferkamp, Christian Blank, James Larkin, Claus Garbe, Dirk Schadendorf, Paul Lorigan, Bastian Schilling
• E-Jahr: 2019
• Jahr: 15 June 2019
• Umfang: 9 S.
• Fussnoten: Gesehen am 28.08.2019
• Titel Quelle: Enthalten in: European journal of cancer
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1992
• Jahr Quelle: 2019
• Band/Heft Quelle: 116(2019), Seite 207-2154
• ISSN Quelle: 1879-0852
• DOI: doi:10.1016/j.ejca.2019.05.015
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Ipilimumab
• Sach-SW: MAPK
• Sach-SW: Melanoma
• Sach-SW: PD-1
• Sach-SW: Second-line treatment
• K10plus-PPN: 1672357454

Abstract

Objectives - 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. - Methods - 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. - Results - 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. - Conclusions - 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.