KRAS is the most frequently mutated oncogene, but despite being discovered more than 40 years ago, it has long been considered to be undruggable.1 The KRASG12C oncogene is present in approximately 13% of non–small-cell lung cancer (NSCLC) cases.1 Sotorasib, a first-in-class small molecule, binds to KRASG12C to turn off unregulated cell division and tumorigenesis.1 In the registrational phase 2 CodeBreaK trial, 126 patients pretreated with a median of 2 prior lines of therapy were treated with oral sotorasib 960 mg once daily for 21-day treatment cycles until their disease progressed.2 There was a 37.1% response rate with a mean duration of 10.0 months, a median progression-free survival of 6.8 months, and a tolerable safety profile in this group.2 The patient-reported outcomes (PROs) from the phase 2 study results were presented at the 2021 American Society of Clinical Oncology annual meeting.
Patients had a 70% compliance rate for the questionnaires used in the study.2 The questionnaires were used to determine changes in global health status/quality of life, physical functioning, and key lung cancer symptoms of chest pain, cough, and dyspnea from baseline to study discontinuation.2 Global health status, quality of life, and physical functioning were maintained over time.2 Appetite loss, constipation, dyspnea, fatigue, insomnia, nausea/vomiting, and pain were all stable or improved with sotorasib use.
Patients were evaluated for the impact of side effects.2 A majority of patients reported they were “not at all” (54.2%-79.2%) or were “a little bit” (8.3%-33.3%) bothered by treatment side effects, while 0% to 7.4% reported being bothered “quite a bit.” No patient reported being “very much” bothered by side effects.2
The positive PRO measures in this study, along with good efficacy and a tolerable safety profile, demonstrate the potential for sotorasib to be beneficial for patients with previously treated 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 A, Wilson F, 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(suppl_15):9057.
