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Optimal Sotorasib Dose for Patients With KRAS G12C-Mutated Advanced Non-Small Cell Lung Cancer
Results from a phase 2 study found that 960 mg of sotorasib is preferable to 240 mg among patients with previously treated KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC).
According to Maximilian Hochmair, MD, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Vienna, Austria, and coauthors, “Sotorasib 960 mg once daily is approved to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer [however] sotorasib exhibits non-dose proportional pharmacokinetics and clinical responses at lower doses.”
In this open-label study, 209 patients with KRAS G12C-mutated locally advanced or metastatic NSCLC were randomized to receive either 960 mg (n = 104) or 240 mg (n = 105) of once daily sotorasib. The primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and pharmacokinetics.
At analysis, ORR was 32.7% in the 960 mg arm and 24.8% in the 240 mg arm. Disease control rate was 86.5% in the 960 mg arm and 81.9% in the 240 mg arm, and median PFS was 5.4 months and 5.6 months, respectively. At a median follow up of 17.5 months, median OS was 13 months in the 960 mg arm and 11.7 months in the 240 mg arm. AUC0-24 and Cmax were 1.3-fold numerically higher in the 960 mg arm. The most frequent treatment-emergent adverse events occurring in ≥ 10% of patients included diarrhea, nausea, increased alanine aminotransaminase, and increased aspartate aminotransferase.
“Sotorasib 960 mg once daily had a more favorable benefit-risk profile than 240 mg,” concluded Dr Hochmair et al. “The safety profile is manageable with label-directed dose modifications.”
Source:
Hochmair MJ, Vermaelen K, Mountzios G, et al. Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC. Eur J Cancer. Published online: July 5, 2024. doi: 10.1016/j.ejca.2024.114204
