Kreft, Sophia and Glutsch, Valerie and Zaremba, Anne and Schummer, Patrick and Mohr, Peter and Grimmelmann, Imke and Gutzmer, Ralf and Meier, Friedegund and Pfoehler, Claudia and Sachse, Michael Max and Meiss, Frank and Forschner, Andrea and Haferkamp, Sebastian and Welzel, Julia and Terheyden, Patrick and Herbst, Rudolf and Utikal, Jochen and Kaatz, Martin and Weishaupt, Carsten and Kreuter, Alexander and Debus, Dirk and Duecker, Pia and Sindrilaru, Anca and Loeffler, Harald and Schley, Gaston and Weichenthal, Michael and Schadendorf, Dirk and Ugurel, Selma and Gesierich, Anja and Schilling, Bastian (2022) MAPKinase inhibition after failure of immune checkpoint blockade in patients with advanced melanoma e An evaluation of the multicenter prospective skin cancer registry ADOREG. EUROPEAN JOURNAL OF CANCER, 167. pp. 32-41. ISSN 0959-8049, 1879-0852
Full text not available from this repository. (Request a copy)Abstract
Objectives: Forty to sixty percent of patients with advanced melanoma show primary resistance to PD-1-based immunotherapy, 30-40% of initial responders also progress. Here, we evaluated the outcome of second-line targeted therapy (TT) after progression on PD-1-based immune checkpoint inhibition (ICI) in BRAFV600-mutated melanoma. In addition, we report data on the activity of re-exposure with PD-1-based regimes. Methods: Patients with advanced (non- resectable stage III or IV, AJCC 2017, 8th edition) melanoma progressing on PD-1-based ICI (nivolumab, pembrolizumab or ipilimumab plus nivolumab) and receiving second-line BRAF plus MEK inhibition were identified from the prospective multicenter skin cancer registry ADOREG. Results: We identified 108 patients with unresectable stage III or stage IV melanoma progressing on first-line ICI (nivolumab, pembrolizumab or ipilimumab plus nivolumab) and receiving second-line combined BRAF/MEK inhibition. Seventy- three percent of the cohort presented with primary PD-1 resistant disease. Median progression-free survival ( PFS) on ICI was 2.6 (95% CI 2.2-2.9) months. Median PFS on subsequent TT was 6.6 (95% CI 5.4 -7.8) months. Median OS from start of second-line TT was 16.0 (95% CI 11.2-20.8) months. The 3-year PFS and OS rates on second-line TT were 16% and 30%. The objective response rate (ORR) and disease control rate (DCR) to TT were 42.6% and 55.6%. In patients with brain metastases, the ORR and DCR were 31.4% and 43.1%. Patients without brain metastases showed an ORR and DCR of 52.6% and 66.7%, respectively. Response to first-line ICI was associated with a numerically higher ORR and DCR to second-line TT and improved OS on TT. Twenty-three patients received third-line ICI of whom two patients showed an objective response. Conclusions: BRAF plus MEK inhibition shows meaningful activity and outcome in patients with advanced melanoma resistant to anti-PD-1- based immunotherapy. Rates of long- term benefit and survival in our study were similar to those reported for treatment-nai<spacing diaeresis>ve patients receiving first-line MAPKi.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DABRAFENIB PLUS TRAMETINIB; SURVIVAL; EFFICACY; Melanoma; PD-1 resistance; MAPK; Second-line treatment; Third-line treatment |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2023 06:29 |
| Last Modified: | 14 Dec 2023 06:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58729 |
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