PMID- 31212163 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20231213 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 116 DP - 2019 Jul TI - Efficacy of PD-1-based immunotherapy after radiologic progression on targeted therapy in stage IV melanoma. PG - 207-215 LID - S0959-8049(19)30318-1 [pii] LID - 10.1016/j.ejca.2019.05.015 [doi] AB - 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. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Kreft, Sophia AU - Kreft S AD - Department of Dermatology, Venereology and Allergology, University Hospital Wurzburg, Wurzburg, Germany. FAU - Gesierich, Anja AU - Gesierich A AD - Department of Dermatology, Venereology and Allergology, University Hospital Wurzburg, Wurzburg, Germany. FAU - Eigentler, Thomas AU - Eigentler T AD - Department of Dermatology, University Medical Center Tubingen, Tubingen, Germany. FAU - Franklin, Cindy AU - Franklin C AD - Department of Dermatology, University Hospital Cologne, Cologne, Germany. FAU - Valpione, Sara AU - Valpione S AD - University of Manchester and Christie NHS Foundation Trust, Manchester, UK. FAU - Ugurel, Selma AU - Ugurel S AD - Department of Dermatology, University Hospital, Essen, Germany; German Cancer Consortium of Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Utikal, Jochen AU - Utikal J AD - Department of Dermatology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Haferkamp, Sebastian AU - Haferkamp S AD - Department of Dermatology, University Hospital Regensburg, Regensburg, Germany. FAU - Blank, Christian AU - Blank C AD - Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. FAU - Larkin, James AU - Larkin J AD - The Royal Marsden NHS Foundation Trust, London, UK. FAU - Garbe, Claus AU - Garbe C AD - Department of Dermatology, University Medical Center Tubingen, Tubingen, Germany. FAU - Schadendorf, Dirk AU - Schadendorf D AD - Department of Dermatology, University Hospital, Essen, Germany; German Cancer Consortium of Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Lorigan, Paul AU - Lorigan P AD - University of Manchester and Christie NHS Foundation Trust, Manchester, UK. FAU - Schilling, Bastian AU - Schilling B AD - Department of Dermatology, Venereology and Allergology, University Hospital Wurzburg, Wurzburg, Germany. Electronic address: schilling_b@ukw.de. LA - eng PT - Journal Article DEP - 20190615 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Ipilimumab) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 31YO63LBSN (Nivolumab) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/therapeutic use MH - Antineoplastic Agents, Immunological/*therapeutic use MH - Drug Resistance, Neoplasm/drug effects MH - Female MH - Humans MH - Immunotherapy/*methods MH - Ipilimumab/therapeutic use MH - Male MH - Melanoma/*drug therapy/mortality MH - Middle Aged MH - Molecular Targeted Therapy/methods MH - Neoplasm Recurrence, Local/*drug therapy/mortality MH - Nivolumab/therapeutic use MH - Programmed Cell Death 1 Receptor/antagonists & inhibitors MH - Retrospective Studies MH - Salvage Therapy/*methods MH - Skin Neoplasms/*drug therapy/mortality MH - Treatment Outcome MH - Melanoma, Cutaneous Malignant OTO - NOTNLM OT - Ipilimumab OT - MAPK OT - Melanoma OT - PD-1 OT - Second-line treatment EDAT- 2019/06/19 06:00 MHDA- 2020/06/02 06:00 CRDT- 2019/06/19 06:00 PHST- 2019/03/28 00:00 [received] PHST- 2019/05/12 00:00 [revised] PHST- 2019/05/13 00:00 [accepted] PHST- 2019/06/19 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] PHST- 2019/06/19 06:00 [entrez] AID - S0959-8049(19)30318-1 [pii] AID - 10.1016/j.ejca.2019.05.015 [doi] PST - ppublish SO - Eur J Cancer. 2019 Jul;116:207-215. doi: 10.1016/j.ejca.2019.05.015. Epub 2019 Jun 15.