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Treatment patterns and outcomes in KRASG12C-positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study.
Barghout, Samir H; Zhan, Luna Jia; Raptis, Starvroula; Al-Agha, Faisal; Esfahanian, Niki; Popovacki, Aimee; Kasymjanova, Goulnar; Proulx-Rocray, Francis; Chan, Sze Wah Samuel; Richardson, Matthew; Brown, M Catherine; Patel, Devalben; Dean, Michelle Liane; Navani, Vishal; Moore, Erica; Carvery, Lane; Yan, Elizabeth; Goldshtein, Daniel; Cleary-Gosine, Jasmine; Gibson, Amanda Jw; Hubley, Lynn; Balaratnam, Karmugi; Ngo, Tran; Gill, Azee; Black, Morgan; Sacher, Adrian; Bradbury, Penelope A; Shepherd, Frances A; Leighl, Natasha; Cheema, Parneet; Kuruvilla, Sara; Agulnik, Jason; Banerji, Shantanu; Juergens, Rosalyn; Blais, Normand; Cheung, Winson; Wheatley-Price, Paul; Liu, Geoffrey; Snow, Stephanie.
Afiliação
  • 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.
Lung Cancer ; 194: 107898, 2024 Aug.
Article em En | MEDLINE | ID: mdl-39074423
ABSTRACT

OBJECTIVES:

KRAS mutations, particularly KRASG12C, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRASG12C-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 KRASG12C-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 KRASG12C-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. KRASG12C-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 KRASG12C-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 KRASG12C-targeted therapies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas p21(ras) / Carcinoma Pulmonar de Células não Pequenas / Inibidores de Checkpoint Imunológico / Neoplasias Pulmonares Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas p21(ras) / Carcinoma Pulmonar de Células não Pequenas / Inibidores de Checkpoint Imunológico / Neoplasias Pulmonares Idioma: En Ano de publicação: 2024 Tipo de documento: Article