Non–small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths and comprises 85% of lung cancer cases. The most common subtype is adenocarcinoma, accounting for 40% of all lung cancer cases. In adenocarcinoma, the KRAS viral oncogene is the most common mutation, with the KRAS G12C mutation being the most common (13% of lung adenocarcinomas). KRAS G12C mutation leads to accelerated oncogenic pathways and proliferation of cell growth. Sotorasib, adagrasib, and JNJ-74699157 are inhibitors of the KRAS G12C mutation. Sotorasib targets KRAS G12C and irreversibly inhibits it by binding it in the inactive GDP-bound state and inhibiting KRAS signaling.
In the phase 2 CodeBreaK 100 clinical trial, sotorasib demonstrated clinical efficacy in previously treated NSCLC harboring the KRAS G12C mutation. Sotorasib received accelerated approval by the FDA in 2021 for the treatment of patients with previously treated advanced KRAS G12C–mutated NSCLC. A recently published case study reported the use of sotorasib as first-line treatment for advanced KRAS G12C–mutated NSCLC in an 80-year-old woman. The patient was a former smoker with a medical history of chronic obstructive pulmonary disease (COPD), atrial fibrillation, hypertension, and Crohn disease. The patient had a fall that resulted in fractured ribs and pneumothorax, which required the placement of a chest tube. During chest computed tomography (CT) to evaluate injuries from the fall, the patient was found to have a 2.1-cm lung nodule. Further imaging studies found a 2.2-cm mass in the anterior medial right upper lobe. Biopsy of this nodule demonstrated poorly differentiated carcinoma, and further testing found poorly differentiated NSCLC with the KRAS G12C mutation. Because the patient was a poor surgical candidate due to COPD and poor pulmonary reserve, she received stereotactic body radiotherapy. Disease progression was found on imaging, but no metastatic disease was found with brain magnetic resonance imaging. Due to the patient’s advanced age, poor performance status, and multiple comorbidities, she was not a candidate for platinum-based chemotherapy or immunotherapy. Sotorasib was determined to be the most feasible option for this patient. The patient received 960 mg of oral sotorasib daily and tolerated it well with no significant toxicities. At 3-month evaluation, positron emission tomography (PET)/CT imaging found the patient had a complete response to treatment with complete resolution of all sites. On repeat PET/CT scan 6 months after sotorasib treatment initiation, the response was stable, and the patient continued treatment with a stable quality of life.
Source: Iska S, Alley EW. Sotorasib as first-line treatment for advanced KRAS G12C-mutated non-small cell lung carcinoma: a case report. Case Rep Oncol. 2023;16(1):177-181.