Sotorasib in Advanced KRAS G12C-Mutated NSCLC: Results From the Global Expanded Access Program, Including Patients With Poor Performance Status and a History of CNS Metastases

Introduction Data from two global protocols under the expanded access program, Study-436 and Study-442, evaluating the safety and efficacy of sotorasib in patients with advanced KRAS G12C-mutated NSCLC beyond the traditional registrational trial setting are presented. Methods Patients were enrolled in 90 centers globally. Baseline characteristics and safety data for Study-436 and Study-442 and efficacy data for Study-436 were estimated. All data were summarized descriptively. Results A total of 268 patients (n = 150 [Study-436] and n = 118 [Study-442]) received oral sotorasib (960 mg daily). At baseline, 21.3% and 31.0% of patients had Eastern Cooperative Oncology Group performance status (ECOG PS) 2 and a history of central nervous system (CNS) metastases, respectively. Treatment-related adverse events occurred in 64.9% of patients; diarrhea (31.3%) was the most common. The incidence of treatment-related adverse events was similar between patients with ECOG PS 0 to 1 (67.8%) and PS 2 (54.4%) and those with (69.9%) and without (62.7%) a history of CNS metastases. The median real-world progression-free survival and overall survival was 6.3 and 9.5 months, respectively. The median real-world progression-free survival was numerically similar in patients with ECOG PS 0 to 1 versus PS 2 (6.5 versus 5.6 mo) and in patients with versus without a history of CNS metastases (5.7 versus 6.5 mo); median overall survival followed similar trends. Improvement from ECOG PS 2 to ECOG PS 0 to 1 was observed by the end of first cycle of treatment (57.9%). Conclusions Safety and efficacy outcomes of sotorasib in this study were not affected with ECOG PS 2 and the history of CNS metastases and were consistent with those reported in key clinical trials.