Real-World Therapy with Pembrolizumab: Outcomes and Surrogate Endpoints for Predicting Survival in Advanced Melanoma Patients in Germany

Cancers

Dirk Schadendorf¹  Selma Ugurel¹  Julia Welzel²  Chalid Assaf³  Thomas Eigentler³  Jens Ulrich⁴  Jessica C. Hassel⁵  Marc Bender⁶  Peter Mohr⁶  Gaston Schley⁷  Rudolf Herbst⁸  Ralf Gutzmer⁹  Claudia Pföhler^1,10  Imke Grimmelmann^1,11  Michael Weichenthal^1,12  Axel Hauschild^1,12  Katharina C. Kähler^1,12  Carsten Weishaupt^1,13  Ulrike Leiter^1,14  Carmen Loquai^1,15  Patrick Terheyden^1,16  Sebastian Haferkamp^1,17  Carola Berking^1,18  Alexander Kreuter^1,19  Jochen Utikal^2,20  Anja Rudolph^2,21  Maximo Schiavone^2,21  Clemens Krepler^2,22  Ruixuan Jiang^2,22  Sheenu Chandwani^2,22  Emilie Scherrer^2,22  Friedegund Meier^2,23 

[1] Clinic for Dermatology, Venereology and Allergy, University of Essen, 45147 Essen, Germany;Department of Dermatology and Allergology, University Hospital Augsburg, 86156 Augsburg, Germany;Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité—Universitätsmedizin Berlin, 10117 Berlin, Germany;Department of Dermatology and Allergy, Skin Cancer Center, 06484 Quedlinburg, Germany;Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany;Department of Dermatology, Elbe Kliniken Buxtehude, 21614 Buxtehude, Germany;Department of Dermatology, HELIOS Hospital Schwerin, 19055 Schwerin, Germany;Department of Dermatology, Helios Klinikum Erfurt, 99089 Erfurt, Germany;Department of Dermatology, Johannes Wesling Medical Center, Ruhr University Bochum, Campus Minden, 32429 Minden, Germany;Department of Dermatology, Saarland University Medical School, 66123 Homburg, Germany;Department of Dermatology, Skin Cancer Center Hannover, Hannover Medical School, 30625 Hannover, Germany;Department of Dermatology, Skin Cancer Center, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany;Department of Dermatology, University Hospital Münster, 48149 Münster, Germany;Department of Dermatology, University Hospital Tuebingen, 72076 Tuebingen, Germany;Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany;Department of Dermatology, University of Lübeck, 23562 Lübeck, Germany;Department of Dermatology, University of Regensburg, 93040 Regensburg, Germany;Department of Dermatology, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen EMN, Deutsches Zentrum Immuntherapie, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany;Department of Dermatology, Venereology and Allergology, HELIOS St. Elisabeth Hospital Oberhausen, University Witten/Herdecke, 46045 Oberhausen, Germany;Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany;IQVIA, 60549 Frankfurt, Germany;Merck & Co., Inc., Kenilworth, NJ 07033, USA;Skin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases, 01307 Dresden, Germany;

关键词: advanced melanoma;    surrogate endpoint;    real-world evidence;    overall survival (OS);    time to next treatment (rwTtNT);    pembrolizumab;   

DOI  :  10.3390/cancers14071804

来源: DOAJ

【 摘 要 】

Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman’s rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0–35.4) months, the rwPFS was 3.9 months (95%CI 3.5–4.9), the rwTtNT was 10.7 months (95%CI 9.0–12.9), and the rwToT was 6.2 months (95%CI 5.1–6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints.

【 授权许可】

Unknown