KRAS is the most common mutated oncogene and it has long been thought to be untreatable, despite being discovered more than 40 years ago.1 Approximately 13% of patients with non–small-cell lung cancer (NSCLC) have the KRASG12C mutation.1 In KRASG12C, the glycine-to-cysteine mutation at position 12 favors the active form of the KRAS protein, resulting in a KRAS oncoprotein that is primarily guanosine triphosphate–bound, which promotes tumor cell proliferation.1 Sotorasib, a first-in-class small molecule, inhibits uncontrolled cell proliferation and carcinogenesis by binding to KRASG12C.1 During the registrational phase 2 CodeBreaK 100 trial, 126 patients pretreated with a median of 2 previous lines of therapy were treated with 960 mg oral sotorasib once daily for 21-day treatment cycles until their disease progressed.2 The therapeutic benefit of sotorasib was evident across patient subgroups in the CodeBreaK 100 trial.3 This group had a 37.1% response rate, with a mean duration of 10.0 months, a median progression-free survival of 6.8 months, and an acceptable safety profile.2 The patient-reported outcomes from CodeBreaK were presented at the 2021 American Society of Clinical Oncology Annual Meeting.
The questionnaires utilized in the study were completed by 70% of the patients.2 The questions were used to measure changes in global health status/quality of life, physical functioning, and critical lung cancer symptoms of chest pain, cough, and dyspnea from baseline to study discontinuation.2 Over time, the overall health status, quality of life, and physical functioning were all maintained.2 Sotorasib treatment stabilized or improved appetite loss, constipation, dyspnea, fatigue, sleeplessness, nausea/vomiting, and pain.
The impact of side effects was assessed in patients.2 The majority of patients said they were “not at all” or “a little bit” bothered by treatment-related side effects, whereas only 0% to 7.4% said they were bothered “quite a bit.” No patient stated that side effects troubled them “very much.”2
The positive patient-reported outcome measures in this research, together with acceptable efficacy and a tolerable safety profile, demonstrate that sotorasib has the potential to be useful for previously treated patients with advanced NSCLC.
References
- Hong DS, Fakih MG, Strickler JH, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med. 2020;383:1207-1217.
- Spira AI, Wilson FH, Shapiro G, et al. Patient-reported outcomes (PRO) from the phase 2 CodeBreaK 100 trial evaluating sotorasib in KRAS p.G12C mutated non-small cell lung cancer (NSCLC). J Clin Oncol. 2021;39(suppl 15):Abstract 9057.
- Skoulidis F, Li BT, Govindan R, et al. Overall survival and exploratory subgroup analyses from the phase 2 CodeBreaK 100 trial evaluating sotorasib in pretreated KRAS p.G12C mutated non-small cell lung cancer. J Clin Oncol. 2021;39(suppl 15):Abstract 9003.
