Treatment patterns and outcomes in KRAS G12C -positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study.

Autor: Barghout SH; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt., Zhan LJ; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Raptis S; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Al-Agha F; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Esfahanian N; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Popovacki A; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada., Kasymjanova G; Jewish General Hospital, Montreal, QC, Canada., Proulx-Rocray F; Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada., Chan SWS; Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, ON, Canada., Richardson M; University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada., Brown MC; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Patel D; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Dean ML; Glans-Look Lung Cancer Research, University of Calgary, Calgary, AB, Canada., Navani V; Glans-Look Lung Cancer Research, University of Calgary, Calgary, AB, Canada; Tom Baker Cancer Centre, Calgary, AB, Canada., Moore E; CancerCare Manitoba Research Institute, Winnipeg, MB, Canada., Carvery L; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada., Yan E; Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, ON, Canada., Goldshtein D; Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, ON, Canada., Cleary-Gosine J; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada., Gibson AJ; Glans-Look Lung Cancer Research, University of Calgary, Calgary, AB, Canada., Hubley L; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada., Balaratnam K; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Ngo T; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada., Gill A; Brampton Civic Hospital, William Osler Health System, Brampton, ON, Canada., Black M; London Health Sciences Centre, London, ON, Canada., Sacher A; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Bradbury PA; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Shepherd FA; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Leighl N; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Cheema P; Brampton Civic Hospital, William Osler Health System, Brampton, ON, Canada., Kuruvilla S; London Health Sciences Centre, London, ON, Canada., Agulnik J; Jewish General Hospital, Montreal, QC, Canada., Banerji S; CancerCare Manitoba Research Institute, Winnipeg, MB, Canada., Juergens R; Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, ON, Canada., Blais N; Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada., Cheung W; Glans-Look Lung Cancer Research, University of Calgary, Calgary, AB, Canada; Tom Baker Cancer Centre, Calgary, AB, Canada., Wheatley-Price P; University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada., Liu G; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Electronic address: Geoffrey.Liu@uhn.ca., Snow S; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada. Electronic address: stephanie.snow@nshealth.ca.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2024 Aug; Vol. 194, pp. 107898. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1016/j.lungcan.2024.107898
Abstrakt: Objectives: KRAS mutations, particularly KRAS G12C , are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRAS G12C -selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRAS G12C -positive advanced NSCLC receiving systemic therapy post-ICI treatment.
Methods: From the CAnadian CAncers With Rare Molecular Alterations-Basket Real-world Observational Study (CARMA-BROS), a cohort of 102 patients with KRAS G12C -positive advanced NSCLC across 9 Canadian centers diagnosed between 2015 and 2021 was analyzed. Clinico-demographic and treatment data were obtained from electronic health records. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models.
Results: The patients (median age 66 years; 58 % female; 99 % current/former tobacco exposure; 59 % PD-L1 ≥ 50 %), exhibited heterogeneous treatment patterns post-ICI. Most patients received ICIs as a first-line therapy, with varying subsequent lines including chemotherapy and targeted therapy. In patients receiving systemic therapy post-ICI, median overall survival was 12.6 months, and real-world progression-free survival was 4.7 months. KRAS G12C -selective targeted therapy post-ICI (n = 20) showed longer real-world progression-free survival compared to single-agent chemotherapy (aHR = 0.39, p = 0.012).
Conclusion: This study contributes valuable real-world data on KRAS G12C -positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRAS G12C -targeted therapies.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The study was supported by Amgen. The authors have no other conflicts of interest to declare.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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