Ceritinib treatment demonstrated clinically meaningful whole body and intracranial activity with an acceptable tolerability profile in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung (NSCLC) and brain metastases previously treated with crizotinib.1
Bone metastases are frequent sites of disease progression in patients with ALK mutation-positive NSCLC, including those who have received crizotinib therapy. Because ceritinib displayed 20-fold greater potency than crizotinib in vitro, researchers sought to evaluate the efficacy of ceritinib in crizotinib-pretreated patients with brain metastases in the phase 1 ASCEND-1 trial and the phase 2 ASCEND-2 study.
Researchers enrolled 98 and 100 patients with baseline brain metastases into ASCEND-1 and ASCEND-2, respectively. All patients received ceritinib 750 mg/day orally. Most patients had previously received chemotherapy. A total of 69.4% of patients in ASCEND-1 and 72.0% of patients in ASCEND-2 had received prior radiotherapy to the brain.
Results showed that the overall whole body response rate was 41.8% (95% CI, 31.9 – 52.2) in ASCEND-1 and 32.0% (95% CI, 23.0 – 42.1) in ASCEND-2. Median progression-free survival was 6.7 months (95% CI, 5.4 – 9.5) and 6.8 months (95% CI, 5.4 – 7.4), respectively.
Researchers found that the overall intracranial response rate using pooled data was 37.7% (95% CI, 37.7 – 51.0) with a median intracranial duration of response of 12.8 months (95% CI, 6.9 – not evaluable). The intracranial disease control rate was 73.8% (95% CI, 60.9 – 84.2).
In terms of safety, the most common adverse events were nausea, diarrhea, and vomiting. A total of 17 patients discontinued treatment due to treatment-related toxicity.
- Felip E, Crinó L, Kim D, et al. Whole body and intracranial efficacy of ceritinib in patients (pts) with crizotinib (CRZ) pretreated, ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) and baseline brain metastases (BM): results from ASCEND-1 and ASCEND-2 trials. Poster presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.