2026-04-17T14:56:52Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/138742025-10-24T10:43:36Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Syrigos, Konstantinos author Livi, Lorenzo author Paulus, Astrid author Kim, Sang-We author CHEN, YUANBIN author Dingemans, Anne-Marie author FELIP, ENRIQUETA author 2025-10-16T07:20:15Z 2025-10-16T07:20:15Z 2025-09 Brain metastases; Non-small cell lung cancer; Sotorasib Metàstasis cerebrals; Càncer de pulmó de cèl·lules no petites; Sotorasib Metástasis cerebrales; Cáncer de pulmón de células no pequeñas; Sotorasib Objectives To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib in adults with pretreated advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). Materials and methods Patients with KRAS G12C-mutated NSCLC who progressed after platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1:1 to sotorasib or docetaxel. An exploratory post-hoc analysis evaluated central nervous system (CNS) progression-free survival (PFS) and time to CNS progression in patients with treated and stable brain metastases at baseline. Measures were assessed by blinded independent central review per study-modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Results Of the patients randomly assigned to receive sotorasib (n=171) or docetaxel (n=174), baseline CNS metastases were present in 40 (23%) and 29 (17%) patients, respectively. With a median follow-up of 20.0 months for this patient subgroup, median CNS PFS was longer with sotorasib compared with docetaxel (9.6 vs 4.5 months; hazard ratio, 0.43 [95% CI, 0.20–0.92]; P=0.02). Among patients with baseline treated CNS lesions of ≥10 mm, the percentage of patients who achieved CNS tumor shrinkage of ≥30% was two-fold higher with sotorasib than docetaxel (33.3% vs 15.4%). Treatment-related adverse events among patients with CNS lesions at baseline were consistent with those of the overall study population. Conclusions These results suggest intracranial activity with sotorasib complements the overall PFS benefit observed with sotorasib vs docetaxel, with safety outcomes similar to those in the general CodeBreaK 200 population. Clinical trials registration number: NCT04303780. Representatives of the sponsor, Amgen Inc., designed the clinical study in collaboration with some of the study investigators. Amgen Inc. managed patient data collection at the study sites, maintained the study database, performed the analyses, funded medical writing support, paid publication costs, and paid the open access charge for this article. http://hdl.handle.net/11351/13874 Anomalies cromosòmiques Avaluació de resultats (Assistència sanitària) Medicaments antineoplàstics - Ús terapèutic Pulmons - Càncer - Tractament Cervell - Càncer - Tractament PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents Other subheadings::Other subheadings::/therapeutic use DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung DISEASES::Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms::Brain Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos Otros calificadores::Otros calificadores::/uso terapéutico ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema nervioso::neoplasias del sistema nervioso central::neoplasias cerebrales Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia Intracranial activity of sotorasib vs docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer from a global, phase 3, randomized controlled trial