According to exploratory analysis results from the phase 3 KRYSTAL-12 trial, adagrasib, a KRAS G12C inhibitor, improved efficacy outcomes compared to docetaxel among patients with previously-treated KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC), regardless of the presence of brain metastases. 

These results were presented by Fabrice Barlesi, MD, PhD, Gustave Roussy, Villejuif, France, at the 2024 European Society for Medical Oncology (ESMO) Congress. 

In this open-label, multicenter study, researchers enrolled 453 patients with (n = 114) or without (n = 339) brain metastases who previously received platinum-based chemotherapy and anti–PD-L1 therapy. Patients were randomized on a 2-to-1 basis to receive either 600 mg of adagrasib twice daily (with brain metastases, n = 78; without brain metastases, n = 223) or 75 mg/m² of docetaxel once every 3 weeks (with, n = 36; without, n = 116). Exploratory systematic efficacy end points included objective response rate (ORR), progression-free survival (PFS), and duration of response. A key secondary end point was safety by baseline brain metastases. 

At a median follow-up of 7.2 months, in the adagrasib arm the ORR was 26.9% in patients with brain metastases and 33.6% in patients without brain metastases. In the docetaxel arm, the ORR was 2.8% in patients with brain metastases and 11.2% in patients without brain metastases. In the adagrasib arm, the median PFS was 4.4 months among patients with brain metastases and 5.9 months among patients without brain metastases, compared to 2.9 months and 3.9 months, respectively, in the docetaxel arm. The median duration of response was 7.4 months and 8.3 months in the adagrasib arm and 5.4 months in the docetaxel arm. 

Treatment-related adverse events were reported by 93.5% of patients in the adagrasib arm and 85.7% of patients in the docetaxel arm, of which 6.5% led to treatment discontinuation in the adagrasib arm and 17.1% led to treatment discontinuation in the docetaxel arm. 

As Dr Barlesi et al concluded, these results are “consistent with benefits observed in all randomized [patients] in KRYSTAL-12.”

Source: 

Barlesi F, Yao W, Duruisseaux M, et al. Adagrasib (ADA) vs docetaxel (DOCE) in patients (pts) with KRASG12C-mutated advanced NSCLC and baseline brain metastases (BM): Results from KRYSTAL-12. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA57