Universität zu Köln

Kreft, Sophia, Gesierich, Anja, Eigentler, Thomas, Franklin, Cindy, Valpione, Sara, Ugurel, Selma, Utikal, Jochen, Haferkamp, Sebastian, Blank, Christian, Larkin, James ORCID: 0000-0001-5569-9523, Garbe, Claus ORCID: 0000-0001-8530-780X, Schadendorf, Dirk, Lorigan, Paul ORCID: 0000-0002-8875-2164 and Schilling, Bastian (2019). Efficacy of PD-1-based immunotherapy after radiologic progression on targeted therapy in stage IV melanoma. Eur. J. Cancer, 116. S. 207 - 216. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

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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 + WMEK 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. (C) 2019 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kreft, Sophia UNSPECIFIED UNSPECIFIED UNSPECIFIED Gesierich, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Eigentler, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Franklin, Cindy UNSPECIFIED UNSPECIFIED UNSPECIFIED Valpione, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED Ugurel, Selma UNSPECIFIED UNSPECIFIED UNSPECIFIED Utikal, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Haferkamp, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Blank, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Larkin, James UNSPECIFIED orcid.org/0000-0001-5569-9523 UNSPECIFIED Garbe, Claus UNSPECIFIED orcid.org/0000-0001-8530-780X UNSPECIFIED Schadendorf, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Lorigan, Paul UNSPECIFIED orcid.org/0000-0002-8875-2164 UNSPECIFIED Schilling, Bastian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-136541
DOI:	10.1016/j.ejca.2019.05.015
Journal or Publication Title:	Eur. J. Cancer
Volume:	116
Page Range:	S. 207 - 216
Date:	2019
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1879-0852
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language METASTATIC MELANOMA; COMBINED NIVOLUMAB; BRAF; IPILIMUMAB; DABRAFENIB; SURVIVAL; OUTCOMES; PEMBROLIZUMAB; TRAMETINIB Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13654