In 3 % to 5 % of cases, lung cancer is associated with ALK rearrangement and can therefore be targeted with the ALK inhibitors crizotinib and ceritinib. While crizotinib is the standard first-line therapy, ceritinib has gained approval for use with patients who are crizotinib-refractory. Ceritinib showed clinical activity in both crizotinib-pretreated and ALK-inhibitor-naïve patients in the single-arm, multicentre, phase II, ASCEND-2 and ASCEND-3 studies [1, 2].
Park et al. presented a combined dataset at the ESMO Asia Congress from both of these studies for the patients with brain metastases at baseline . CNS metastases are a common complication in patients with ALK-positive NSCLC. Seventy-one percent and 40.3 % of the patients had brain lesions at the time of inclusion in ASCEND-2 and ASCEND-3, respectively. Prior radiotherapy to the brain had taken place in 72 % and 54 %, respectively.
At the established dose of 750 mg daily, the median PFS amounted to 6.8 months (ASCEND-2) and 11.0 months (ASCEND-3), by blinded independent central review. The ORRs (as the whole-body response) across these trials were 32.0 % and 60.0 %, respectively. In the patients with active brain lesions selected as the target lesions (e.g., those that progressed following local therapy), the overall intracranial response rates were 39.4 % and 58.8 %, respectively. The intracranial disease control rates exceeded 80 % in both trials.
The safety profile for patients with brain metastases did not differ from that in the overall patient population. This subgroup analysis shows that ceritinib is feasible in patients with brain metastases, as durable intracranial responses can be expected.
- Mok T et al., ASCEND-2: A single-arm, open-label, multicenter phase II study of ceritinib in adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with chemotherapy and crizotinib (CRZ). J Clin Oncol 33, 2015 (suppl; abstr 8059)
- Felip E et al., ASCEND-3: A single-arm, open-label, multicenter phase II study of ceritinib in ALKi-naïve adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 33, 2015 (suppl; abstr 8060)
- Park K et al., Efficacy and safety of ceritinib in patients with ALK-rearranged non-small cell lung cancer and baseline brain metastases – results from ASCEND-2 and ASCEND-3. ESMO Asia 2015, abstract 419O