2026-04-14T02:41:22Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/137312025-10-24T10:23:14Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Chopra, Divyan author Lan, Zhiyi author Waterhouse, David author Wolf, Jürgen author Moradian, Hoora author FELIP, ENRIQUETA author 2025-09-29T08:37:34Z 2025-09-29T08:37:34Z 2025-09 Non-small cell lung cancer; Progression-free survival; Treatment-related adverse event Cáncer de pulmón de células no pequeñas; Supervivencia libre de progresión; Evento adverso relacionado con el tratamiento Càncer de pulmó de cèl·lules no petites; Supervivència lliure de progressió; Esdeveniment advers relacionat amb el tractament Introduction: Sotorasib and adagrasib are the only treatments approved in the USA and Europe for advanced/metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). In the absence of head-to-head trials, a matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy and safety of sotorasib versus adagrasib using phase 3 trials. Methods: Patient-level data from CodeBreaK 200 were reweighted to match the baseline characteristics reported in KRYSTAL-12. The analysis evaluated progression free-survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE). Age, sex, region, prior treatment, brain metastases, and liver metastases were selected for adjustment in the primary analysis per clinical guidance, using an unanchored approach (no common comparator). We conducted sensitivity analyses including additional covariates or anchoring the analysis via common comparator (docetaxel). Additional subgroup analysis was performed in patients with baseline brain metastases, assessing systemic PFS. Results: Following adjustment, the reweighted patient characteristics from CodeBreaK 200 and KRYSTAL-12 were well balanced. In the primary analysis, sotorasib and adagrasib showed similar efficacy: PFS (HR [hazard ratio] 0.93; 95% confidence interval [CI] 0.70-1.22; p = 0.589) and ORR (odds ratio 0.86; 95% CI 0.53-1.38; p = 0.524). Among patients with brain metastases, sotorasib demonstrated a 39% reduced risk of progression compared with adagrasib (HR 0.61; 95% CI 0.38-0.98; p = 0.040). Sotorasib also demonstrated a more favorable safety profile than adagrasib, with lower odds of TRAEs, TRAEs leading to dose reduction or dose interruption, and all eight individual TRAEs evaluated. Sensitivity analyses supported the robustness of base-case results. Conclusion: In this MAIC, sotorasib and adagrasib showed comparable efficacy in previously treated advanced KRAS G12C-mutated NSCLC. Among patients with baseline brain metastases, PFS point estimates favored sotorasib. Sotorasib also demonstrated a favorable overall safety profile. These findings may help inform payer decisions and clinical practice in the treatment of KRAS G12C-mutated NSCLC. This study was funded by Amgen, Inc. The journal’s Rapid Service Fee was funded by Amgen Inc. http://hdl.handle.net/11351/13731 Cervell - Càncer - Tractament Avaluació de resultats (Assistència sanitària) Anomalies cromosòmiques Medicaments antineoplàstics - Ús terapèutic - Efectes secundaris Pulmons - Càncer - Tractament CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents Other subheadings::Other subheadings::Other subheadings::/adverse effects DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung Other subheadings::Other subheadings::Other subheadings::/drug therapy PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival DISEASES::Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms::Brain Neoplasms COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos 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 Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema nervioso::neoplasias del sistema nervioso central::neoplasias cerebrales Matching-Adjusted Indirect Comparison of Sotorasib Versus Adagrasib in Previously Treated Advanced/Metastatic Non-Small Cell Lung Cancer Harboring KRAS G12C Mutation