Alectinib Promising Against CNS Metastases In ALK-Positive NSCLC Patients

Patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer that has spread to the brain could benefit from treatment with alectinib

medwireNews: Alectinib has durable efficacy against central nervous system (CNS) metastases in patients with crizotinib -refractory, non-small-cell lung cancer (NSCLC) harbouring anaplastic lymphoma kinase (ALK) rearrangements, findings indicate.

The researchers pooled data from two single-arm phase II trials – NP28761 and NP28673 – that assessed the efficacy and safety of the second-generation ALK inhibitor in patients with advanced or metastatic disease who had progressed on crizotinib. The majority (60%) of the 225 patients in the combined study populations had brain metastases at baseline and were included in the current analysis.

Among the 50 participants with measureable CNS disease at baseline, treatment with oral alectinib 600 mg twice a day resulted in an independent review committee-assessed CNS objective response rate (ORR) of 64%, of which 11 were complete responses. Ninety percent of patients achieved CNS disease control, defined as a complete or partial response or stable disease, with a median duration of response of 10.8 months.

When all 136 patients were considered (ie, those with measurable and nonmeasurable disease), the independently assessed CNS ORR was 42.6%, with 37 complete responses. The CNS disease control rate was 85.3% and the median duration of response in the CNS was 11.1 months.

These findings demonstrate that “alectinib can provide CNS benefit regardless of whether the disease is measurable according to RECIST”, say lead author Shirish Gadgeel, from Karmanos Cancer Institute in Detroit, Michigan, USA, and team.

They also found that the ALK inhibitor has clinical efficacy regardless of radiation history. Specifically, the CNS ORR was 35.8% for the 95 participants who had received prior CNS radiotherapy and 58.5% for the 41 patients without a history of radiotherapy. When the analysis was restricted to patients with measurable baseline brain metastases, the rates rose to 61.8% and 68.8% for those who had and had not received radiotherapy, respectively.

The rates of adverse event-related dose reductions (14.7%) and discontinuation (5.9%) were low and the safety profile was consistent with previous studies, “confirming that alectinib is well tolerated in patients with or without baseline CNS metastases”, the team writes in the Journal of Clinical Oncology.

Given the physiological and neurological toxicities associated with standard whole-brain radiotherapy and the potential for reduced efficacy with stereotactic radiosurgery, Shirish Gadgeel et al conclude: “A systemic drug treatment able to target all brain lesions with minimal toxicity could therefore offer clear advantages versus current standards of care.”


Gadgeel SM, Shaw AT, Govindan R, et al. Pooled analysis of CNS response to alectinib in two studies of pretreated patients with ALK-positive non–small-cell lung cancer. J Clin Oncol; Advance online publication 3 October 2016. doi: 10.1200/JCO.2016.68.4639

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