Among patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC), treatment via Krazati (adagrasib) was associated with superior outcomes when compared to treatment with docetaxel (DOCE), regardless of whether those patients had baseline brain metastases, according to findings from the phase 3 KRYSTAL-12 trial presented at the 2024 ESMO Annual Congress.
The study included 453 patients with KRAS G12C-mutated locally advanced/metastatic NSCLC who had been previously treated with platinum-based chemotherapy and anti-PD(L)1 therapy and who were randomized 2:1 to receive 600 mg twice a day of Krazati orally or 75 mg/m2 every three weeks intravenously.
Patients with treated, neurologically stable brain metastases at baseline were eligible for participation, and 114 patients (25.2%) had baseline brain metastases (78 in the Krazati arm, 36 in the DOCE arm).
Among patients with baseline brain metastases, the median intracranial (within the head) time to progression was 18.6 months in the Krazati arm and not evaluable (meaning fewer than half of the patients had experienced intracranial progression) in the DOCE arm.
At a median follow-up of 7.2 months, median PFS was 4.4 months in the Krazati arm and 2.9 months in the DOCE arm among patients with brain metastases, and 5.9 months in the Krazati arm and 3.9 months in the DOCE arm in patients without brain metastases.
Furthermore, the objective response rate (ORR) was higher in the Krazati versus DOCE arm among patients both with (26.9% versus 2.8%) and without (33.6% versus 11.2%) baseline brain metastases, as was the median duration of response (DOR) for patients with (7.4 versus 5.4 months) and without (8.3 versus 5.4 months) baseline brain metastases.
Treatment-related side effects were also reported to be comparable across treatment arms and irrespective of the presence of baseline brain metastases. Among patients with brain metastases, 94% of patients in the Krazati arm and 86% of patients in the DOCE arm experienced a treatment-related side effect, while among patients without brain metastases 94% and 87% of patients in the Krazati and DOCE arms, respectively, experienced a treatment-related side effect. There were five total treatment-related deaths, four among patients in the in the Krazati arm without brain metastases and one in the DOCE arm with brain metastases.
“[Krazati] demonstrated an improved intracranial efficacy over docetaxel in patients with treated, neurologically stable baseline brain metastases,” stated Dr. Fabrice Barlesi, thoracic oncologist, Paris Saclay University and chief executive officer of Gustave Roussy Institute, in a presentation of the findings. “… Systemic overall response rate, duration of response and PFS were numerically greater with [Krazati] compared to docetaxel, regardless of the presence of brain metastases, the safety profiles of [Krazati] and docetaxel were comparable in patients with and without brain metastasis, and were consistent with all randomized patients. Overall, these results clearly reinforce [Krazati] as an efficacious treatment option for patients including with baseline brain metastasis with previously treated KRAS G12C-mutated non-small cell lung cancer.”
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