Higher sotorasib dose reduces risk for death in KRAS-mutant lung cancer
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Key takeaways:
- Patients who received the 960 mg daily dose of sotorasib had a markedly reduced risk for death compared with a 240 mg daily dose.
- Researchers reported a similar safety profile for both doses of sotorasib.
A 960 mg daily dose of sotorasib conferred a longer OS benefit among certain patients with KRAS G12C-mutant advanced non-small cell lung cancer, results from a randomized phase 2 showed.
According to data presented during a European Society for Medical Oncology Virtual Plenary, the higher dose of sotorasib reduced the risk for death by 25% compared with patients who received a 240 mg daily dose.
“Overall, sotorasib 960 mg once daily provides a more favorable benefit-risk profile compared with sotorasib 240 mg once daily,” Maximilian Hochmair, MD, a specialist in respiratory medicine at Klinik Floridsdorf in Vienna, said during a presentation “These data are reinforced by the CodeBreaK 300 study of sotorasib 960 mg or 240 mg plus panitumumab versus standard of care in KRAS G12C metastatic colorectal cancer, recently published in The New England Journal of Medicine, where the 960 mg dose appeared to yield more clinical benefit than the 240 mg dose.”
Background and methodology
Sotorasib (Lumakras, Amgen) is a first-in-class KRAS inhibitor that has received accelerated or full approval in more than 50 countries for pretreated KRAS G12C-mutant advanced non-small cell lung cancer at a dose of 960 mg once daily. Researchers conducted a randomized, open-label phase 2 study to assess the safety and efficacy profiles of once daily sotorasib in certain patients at doses of either 960 mg or 240 mg.
The CodeBreaK 100 trial included 209 adults with previously treated, advanced KRAS G12C-positive non-small cell lung cancer who had previously received a PD-L1 inhibitor and/or platinum-based chemotherapy.
Researchers randomly assigned 104 adults (median age, 65; 46.2% women) to receive 960 mg sotorasib once daily, with an additional 105 adults (median age, 65; 44.8% women) receiving 240 mg once daily, until disease progression or unacceptable toxicity.
Objective response rate per RESIST 1.1 and safety served as the study’s primary endpoints. Secondary endpoints included duration of response, time to response, PFS, OS, pharmacokinetics and disease control rate.
Results
Researchers noted an improvement in confirmed ORR among patients in the higher dose cohort, with patients in the 960 mg group showing an ORR of 32.7% (95% CI, 23.8–42.6) compared with 24.8% (95% CI, 16.9–34.1) in the 240 mg group.
Additionally, researchers noted improvements in disease control rate (86.5% vs. 81.9%) and median duration of response (13.8 months vs. 12.5 months) in the higher-dose group.
Investigators reported median PFS of 5.4 months for patients enrolled in the 960 mg cohort and 5.6 months for patients in the 240 mg cohort (HR = 0.95; 95% CI, 0.67–1.35), whereas those median OS favored the 960 mg dose group (13 vs 11.7 months; HR = 0.75; 95% CI, 0.53–1.07).
Although similar when comparing the two groups, researchers observed a numerically higher incidence of treatment-related adverse events among patients treated with the higher dose of the agent. The most common treatment-related adverse events in both groups included diarrhea and nausea.
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Hochmair M, et al. Sotorasib 960 mg versus 240 mg in pretreated KRAS G12C advanced NSCLC. Presented at: ESMO Virtual Plenary; Nov.16, 2023.
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