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Tytuł:
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Prognostic impact of KRAS mutation status for patients with stage IV adenocarcinoma of the lung treated with first-line pembrolizumab monotherapy.
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Autorzy:
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Noordhof AL; Department of Respiratory Medicine, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, the Netherlands.
Damhuis RAM; Department of Research, Comprehensive Cancer Organization, Plesmanlaan 121, 1066 CX, Utrecht, the Netherlands.
Hendriks LEL; Department of Respiratory Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands.
de Langen AJ; Department of Thoracic Oncology, Netherlands Cancer Institute, NA 1007 MB, Amsterdam, the Netherlands.
Timens W; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
Venmans BJW; Department of Respiratory Medicine, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, the Netherlands.
van Geffen WH; Department of Respiratory Medicine, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, the Netherlands. Electronic address: .
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Źródło:
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Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2021 May; Vol. 155, pp. 163-169. Date of Electronic Publication: 2021 Apr 05.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Limerick : Elsevier Scientific Publishers
Original Publication: Amsterdam, The Netherlands : Elsevier, c1985-
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MeSH Terms:
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Adenocarcinoma*/drug therapy
Adenocarcinoma*/genetics
Carcinoma, Non-Small-Cell Lung*
Lung Neoplasms*/drug therapy
Lung Neoplasms*/genetics
Proto-Oncogene Proteins p21(ras)*/genetics
Antibodies, Monoclonal, Humanized ; B7-H1 Antigen/genetics ; B7-H1 Antigen/metabolism ; Humans ; Lung/metabolism ; Mutation ; Netherlands ; Prognosis ; Protein-Tyrosine Kinases/genetics ; Retrospective Studies
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Contributed Indexing:
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Keywords: Kirsten rat sarcoma; Mono-immunotherapy; Non-small cell lung cancer
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Substance Nomenclature:
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0 (Antibodies, Monoclonal, Humanized)
0 (B7-H1 Antigen)
0 (KRAS protein, human)
DPT0O3T46P (pembrolizumab)
EC 2.7.10.1 (Protein-Tyrosine Kinases)
EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
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Entry Date(s):
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Date Created: 20210410 Date Completed: 20210621 Latest Revision: 20220531
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Update Code:
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20240105
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DOI:
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10.1016/j.lungcan.2021.04.001
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PMID:
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33838467
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Objectives: Monotherapy with pembrolizumab is the preferred first-line treatment for metastatic non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression ≥50 %, without targetable oncogenic drivers. Although targeted therapies are in development for patients with specific Kirsten rat sarcoma (KRAS) mutations, these are not available in daily care yet. It is not clear whether there is a difference in survival on first-line pembrolizumab for patients with a high PD-L1 status with or without a KRAS mutation. We aim to compare this survival based on real-world data.
Materials and Methods: This is a real-world retrospective population-based study using data from the Netherlands Cancer Registry. We selected patients with stage IV lung adenocarcinoma with PD-L1 expression ≥50 % diagnosed between January 2017 and December 2018, treated with first-line pembrolizumab. Patients with EGFR mutations, ALK translocations or ROS1 rearrangements were excluded. The primary outcome parameter was overall survival.
Results: 388 (57 %) of 595 patients had a KRAS mutation. KRAS was seen more frequently in women than in men (65 % versus 49 % respectively, p < 0.001). The median overall survival was 19.2 months versus 16.8 months for patients with and without KRAS mutation, respectively (p = 0.86). Multivariable analysis revealed WHO performance score, number of organs with metastases and PD-L1 percentage as independent prognostic factors. KRAS mutation status had no prognostic influence (hazard ratio = 1.03, 95 % CI 0.83-1.29).
Conclusion: The survival of KRAS mutated versus KRAS wild-type lung adenocarcinoma patients, treated with first-line pembrolizumab monotherapy, is similar, suggesting that KRAS has no prognostic value with respect to treatment with pembrolizumab.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
