58P Real-world intracranial effectiveness of sotorasib in second-line (2L) and beyond (2L+) treatment (tx) of KRAS G12C-mutated non-small cell lung cancer (NSCLC) with brain metastases (BM)

Document Type

Conference Proceeding

Publication Date

4-1-2026

Publication Title

ESMO Open

Keywords

sotorasib, adult, aged, all cause mortality, brain metastasis, China, clinical trial, conference abstract, controlled study, data warehouse, electronic health record, expert witness, female, follow up, human, lung cancer, male, middle aged, non small cell lung cancer, overall survival, parttime employment, product vigilance, progression free survival, stereotactic radiosurgery, transgene, travel, United States, wolf

Abstract

Background: In this study, we evaluated real-world clinicopathological characteristics, median overall survival (OS), and median intracranial progression-free survival (iPFS) in patients (pts) with previously untreated and treated BM who initiated sotorasib in 2L and 2L+ settings. Methods: Pts from a US-based electronic health record–derived de-identified Flatiron Health Enhanced Datamart treated with sotorasib as 2L+ between May 28, 2021, and February 28, 2024, and evidence of treated or untreated BM either before or within 7 days of sotorasib initiation were included in this study. The data cutoff date was February 28, 2025, allowing for a minimum of 12 months of follow-up for estimating OS and iPFS. Patient demographic and clinical characteristics were described. OS, measured from sotorasib initiation to death, and iPFS, defined as the time from sotorasib initiation to the earliest of intracranial progression or death from any cause, were assessed. Outcomes were further analyzed in pts receiving sotorasib as 2L only. Median OS was also evaluated in pts with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1. Results: A total of 135 pts with BM received 2L+ sotorasib, of which 86 received 2L sotorasib. Overall, baseline demographics and disease characteristics of pts were similar in 2L and 2L+ analysis sets. Most pts in the 2L and 2L+ analysis sets had prior anti-PD-(L)1 tx (75.6%; 78.5%) and had an ECOG PS 0–1 (52.3%; 54.9%). Pts in the 2L and 2L+ analysis sets had treated BM (88.4%; 88.1%) and untreated BM (11.6%; 11.9%); 52.3% and 52.6% of pts with treated BM had received stereotactic radiosurgery. The median OS of 2L and 2L+ sotorasib was similar (9.5 months; 9.4 months). In pts with ECOG PS 0–1, median OS of 11.2 and 10.5 months were observed for 2L and 2L+, respectively. The median iPFS for both 2L and 2L+ sotorasib was 7.0 months. Conclusions: In 2L and 2L+ settings, real-world evidence supports sotorasib as a viable option in pts with KRAS G12C-mutated advanced NSCLC with BM, suggesting that sotorasib has intracranial activity and clinically meaningful outcomes consistent with clinical trials experience. Editorial acknowledgement: Medical writing assistance was provided by Advait A. Joshi, PhD, of Cactus Life Sciences (part of Cactus Communications) and Tim Harrison, PharmD, CMPP, of Amgen Inc. Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc. Disclosure: E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen, Regeneron, Pierre Fabre, Genmab, Apollomics, BeiGene, PharmaMar, GSK; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi Sankyo, Illumina, AbbVie; Financial Interests, Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Financial Interests, Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche, Transgene; Other, Personal, Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP); Other, Personal, Other, Director of Research and Innovation: Catalan Institute of Oncology. J. Sabari: Financial Interests, Personal, Other, Consulting or advising fees: AstraZeneca, AbbVie, EMD Serono, Genentech, Janssen Johnson & Johnson, Jazz, Loxo, Lilly, Mirati/Bristol Myers Squibb, Pfizer, Regeneron, Revolution Medicines, Sanofi Genzyme, and Takeda; Financial Interests, Institutional, Research Grant: Janssen, Johnson & Johnson, Loxo, Lilly, Mirati/Bristol Myers Squibb, Regeneron, and ORIC. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Amgen, Bayer, AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Boehringer Ingelheim, Pfizer, MSD; Financial Intere ts, Institutional, Other, IDMC: Roche; Financial Interests, Institutional, Expert Testimony: Mirati; Financial Interests, Institutional, Invited Speaker: Eli Lilly, BeOne, Johnson & Johnson, Lilly, Amgen, Daiichi Sankyo, Roche, Roche, JNJ, Mirati, Bayer, Eli Lilly, Amgen, Boehringer Ingelheim, Merus, Revolution Medicine; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Personal, Other, Chair Scientific Chair Council EORTC: EORTC; Non-Financial Interests, Personal, Member: IASLC, ASCO, AACR, ERS; Non-Financial Interests, Personal, Leadership Role: EORTC. S. Gadgeel: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Genentech/Roche, Bristol Myers Squibb, Pfizer, Daiichi Sankyo, Lilly, Merck, Gilead, Regeneron, Takeda, Bayer, Astellas, AbbVie, Merck, Johnson & Johnson, Boehringer Ingelheim, Nuvation; Financial Interests, Personal, Other, Data Safety Monitoring Board: AstraZeneca; Financial Interests, Personal, Other, Travel support to attend WCLC 2023 for oral presentation: Mirati, Merck; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Nuvalent, Tango Pharmaceuticals, Genentech/Roche, Genmab, Nimbus, Daiichi Sankyo, Janssen, Amgen, Bayer, Mirati, Pfizer, D3 Bio, Debio Pharma, Arrivent, Grail, Iovance, Jacobio, Kymera, Keza Pharmaceuticals, AbbVie, Amgen, Novita, Regeneron, Turning Point, Verastem, Lilly, Johnson & Johnson, Bristol Myers Squibb International, Beijing Avistone Biotechnology, Debiopharm, Janux, Novita, Prelude Therapeutics, Revolution Medicine; Financial Interests, Personal, Invited Speaker: Arcus. J. Lee, R. Gupta, R. Jassim, C. Ardito-Abraham, M.A. Mesa Frias: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. J.J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda, Nuvalent, Pierre Fabre, Merck, Mirati, BeiGene, Genmab, Ellipses Pharma, Disco Pharmaceuticals GmbH, Zuelling Pharma, AbbVie; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer, AstraZeneca, Amgen. S.B. Goldberg: Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Mirati, and Adela; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Daiichi Sankyo, Johnson & Johnson, Summit Therapeutics, Merck, Regeneron, Bayer, Synthekine, and Tubulis. All other authors have declared no conflicts of interest.

Volume

11

Find It @ Sladen

Share

COinS