Alectinib May Have CNS Benefits in Patients with NSCLC

Alectinib, a new generation anaplastic lymphoma kinase (ALK) inhibitor, may significantly improve systemic and central nervous system (CNS) efficacy compared with crizotinib in previously treated ALK-positive non-small cell lung cancer (NSCLC) patients. In addition, this agent appears to have a favorable safety profile when compared with crizotinib, according to new data presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain. Data from two separate phase III studies demonstrated that alectinib may have a special benefit in terms of CNS activity in patients with advanced NSCLC involving an ALK mutation.

Findings from the ALUR trial and a secondary analysis of the ALEX trial showed alectinib can significantly decrease CNS progression of NSCLC, in both the first- and  second-line treatment settings. ALUR trial investigator Silvia Novello from the University of Turin in Italy said alectinib may now be considered a new standard of care for patients with previously treated ALK-positive NSCLC.

The ALUR study included 107 ALK-positive NSCLC patients whose disease had progressed after a previous first-line combination treatment of both platinum-based chemotherapy and crizotinib. They were randomly assigned to second-line therapy with either standard relapse chemotherapy or alectinib. At data cut-off, the median follow-up was 6.5 months in the patients receiving alectinib and 5.8 months in the chemotherapy arm. The treatment durations were significantly different in the two arms, however. The median treatment duration was 20.1 weeks for patients receiving alectinib compared with only 6 weeks in the chemotherapy arm.

The median progression free survival (PFS) was significantly longer in the alectinib group compared with the chemotherapy group (9.6 vs 1.4 months), with a marked difference in CNS response. Among patients who had measurable CNS disease at baseline, the CNS overall response rate was 54.2% in those treated with alectinib compared with 0% in the chemotherapy group. The safety profile of alectinib compared favorably with chemotherapy, despite the substantially longer duration of treatment for patients on alectinib, according to the researchers.

The latest data from the ALEX trial was also presented at the ESMO meeting and the focus was on 122 patients who had CNS metastases at baseline. In this trial, patients were randomized 1:1 to alectinib 600 mg or crizotinib 250 mg (both twice daily) until disease progression, toxicity, withdrawal, or death.

The analysis showed that alectinib had a protective effect in the CNS and it had significant superior CNS activity compared with crizotinib in previously untreated advanced ALK-positive NSCLC. This was the case regardless of prior radiotherapy in this group of 122 patients.