A Multicenter Retrospective Chart Review of Clinical Outcomes Among Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer.

Autor: Iams WT; Vanderbilt University Medical Center, Nashville, TN. Electronic address: wade.t.iams@vumc.org., Balbach ML; Vanderbilt University Medical Center, Nashville, TN., Phillips S; Vanderbilt University Medical Center, Nashville, TN., Sacher A; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Bestvina C; University of Chicago, Chicago, IL., Velcheti V; New York University, NY, NY., Wang X; University of Pennsylvania, Philadelphia, PA., Marmarelis ME; University of Pennsylvania, Philadelphia, PA., Sethakorn N; University of Wisconsin, Madison, WI., Leal T; Emory University, Atlanta, GA., Sackstein PE; Georgetown University, Washington DC, USA., Kim C; Georgetown University, Washington DC, USA., Robinson MA; Kingston Health Sciences Centre, Kingston, Ontario, Canada., Mehta K; University of Kansas, Kansas City, KS., Hsu R; University of Southern California, Los Angeles, CA., Nieva J; University of Southern California, Los Angeles, CA., Patil T; University of Colorado, Aurora, CO., Camidge DR; University of Colorado, Aurora, CO.
Jazyk: angličtina
Zdroj: Clinical lung cancer [Clin Lung Cancer] 2023 May; Vol. 24 (3), pp. 228-234. Date of Electronic Publication: 2023 Feb 08.
DOI: 10.1016/j.cllc.2023.01.009
Abstrakt: Background: On May 28, 2021, the United States Food and Drug Administration (FDA) granted accelerated approval to sotorasib for second-line or later treatment of patients with locally advanced or metastatic KRAS G12C mutant non-small cell lung cancer (NSCLC). This was the first FDA-approved targeted therapy for this patient population. Due to a paucity of real world data describing clinical outcomes in patients with locally advanced or metastatic KRAS G12C mutated NSCLC in the second-line or later, we sought to compile a large, academic medical center-based historical dataset to clarify clinical outcomes in this patient population.
Materials and Methods: The clinical outcomes of 396 patients with stage IV (n = 268, 68%) or recurrent, metastatic (n = 128, 32%) KRAS G12C mutant NSCLC were evaluated in this multicenter retrospective chart review conducted through the Academic Thoracic Oncology Medical Investigator's Consortium (ATOMIC). Patients treated at 13 sites in the United States and Canada and diagnosed between 2006 and 2020 (30% 2006-2015, 70% 2016-2020) were included. Primary outcomes included real-world PFS (rwPFS) and overall survival (OS) from time of stage IV or metastatic diagnosis, with particular interest in patients treated with second-line docetaxel-containing regimens, as well as clinical outcomes in the known presence or absence of STK11 or KEAP1 comutations.
Results: Among all patients with stage IV or recurrent, metastatic KRAS G12C mutant NSCLC (n = 201 with KRAS G12C confirmed prior to first line systemic therapy), the median first-line rwPFS was 9.3 months (95% CI, 7.3-11.8 months) and median OS was 16.8 months (95% CI, 12.7-22.3 months). In this historical dataset, first line systemic therapy among these 201 patients included platinum doublet alone (44%), PD-(L)1 inhibitor monotherapy (30%), platinum doublet chemotherapy plus PD-(L)1 inhibitor (18%), and other regimens (8%). Among patients with documented second-line systemic therapy (n = 123), the second-line median rwPFS was 8.3 months (95% CI, 6.1-11.9 months), with median rwPFS 4.6 months (95% CI, 1.4-NA) among 10 docetaxel-treated patients (9 received docetaxel and 1 received docetaxel plus ramucirumab). Within the total study population, 49 patients (12%) had a co-occurring STK11 mutation and 3 (1%) had a co-occurring KEAP1 mutation. Among the 49 patients with a co-occurring KRAS G12C and STK11 mutation, median rwPFS on first-line systemic therapy (n = 23) was 6.0 months (95% CI, 4.7-NA), and median OS was 14.0 months (95% CI, 10.8-35.3 months).
Conclusion: In this large, multicenter retrospective chart review of patients with KRAS G12C mutant NSCLC we observed a relatively short median rwPFS of 4.6 months among 10 patients with KRAS G12C mutant NSCLC treated with docetaxel with or without ramucirumab in the second-line setting, which aligns with the recently reported CodeBreak 200 dataset.
Competing Interests: Disclosure WTI reports serving as a consultant for Bristol Myers Squibb, Takeda, Janssen, Genentech, Jazz Pharma, G1 Therapeutics, Mirati, OncLive, Clinical Care Options, Chardan, Outcomes Insights, Cello Health, and Curio Science. AS reports consulting/research funding from Genentech, AstraZeneca, and honoraria/consulting from Amgen. CK has served as a consultant for Novartis, Janssen, Astrazeneca, Sanofi, PierianDx, Diffuse pharmaceuticals, Mirati, and Jazz Pharmaceuticals. RH is a consultant for Targeted Healthcare Communications. JN reports consulting for Aadi Biosciences, Astra Zeneca, Bristol Myers Squibb, Fujirebio, G1 Therapeutics, Genentech, Mindmed, Naveris, Takeda, Western Oncolytics, research support from Genentech and Merck, intellectual property from Cansera, and ownership interests with Cansera, Epic Sciences, Indee Bio, and Quantgene. DRC reports advisory roles / Ad hoc advisory boards/consultations 2022: Appolomics (SRC), AstraZeneca/Daiichi (ILD adjudication committee), Beigene (DSMB) Dizal, EMD Serono, Elevation, Hengrui, (DSMB), Hummingbird, Medtronic, Mersana (ILD adjudication committee), Mirati, Nalo Therapeutics, Onkure, Roche, Takeda; 2021: Abbvie, Amgen, Anheart, Apollomics (SRC), AstraZeneca (SRC/SC), Beigene (DSMC), Bio-Thera (DSMB), Blueprint, Daiichi-Sankyo (ILD adjudication committee), Elevation (SRC), Eli Lilly (DSMB and NCCN), EMD Serono, Helsinn (DSMB), Hengrui (DSMC), Janssen, Kestrel (SAB, Shares), Mersana, Nuvalent (SAB), Puma (NCCN), Ribon, Roche/Genentech, Sanofi, Seattle Genetics, Takeda, Turning Point; 2020: Amgen, Anchiarno (SAB), Apollomics (SRC), AstraZeneca, Bio-Thera (DSMB), BMS, Daiichi-Sankyo (ILD adjudication committee), Eisai, EMD Serono, Elevation (SRC), Eli Lilly, GSK, Helssin, Janssen, Onkure, Mersana, Pfizer, Qilu, Roche, Sanofi, Seattle Genetics, Takeda. MB, SP, CB, VV, MM, TL, PES, AR, KM, NS, XW, and TP report no conflicts of interest.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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