ALECTINIB FOR ALK+ NSCLC WITH BRAIN METASTASES

NEW YORK (Reuters Health) - Alectinib (Alecensa, Genentech) shows efficacy against CNS metastases in crizotinib-refractory patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), according to pooled data from two phase II studies sponsored by Hoffmann-La Roche.

Dr. D. Ross Camidge told Reuters Health by email, "In recent years the idea of the brain as a vital battleground in non-small cell lung cancer has emerged, particularly in the subtypes in which we have been very good at controlling disease in the rest of the body."

"These data," he added, "help to consolidate the impressive activity of alectinib in ALK-positive non-small cell lung cancer that has spread to the brain. Importantly, not only did a high proportion of patients both with and without prior radiation respond in the brain, but responses were prolonged."

In an October 3 online paper in the Journal of Clinical Oncology, Dr. Camidge of the University of Colorado Cancer Center, Denver, and colleagues noted that patients initially respond well to the current standard treatment of crizotinib (Xalkori, Pfizer). However, the CNS is a common site of progression for patients with ALK-positive NSCLC receiving such treatment.

Alectinib, also an ALK inhibitor, has demonstrated activity in the CNS and the team sought to further evaluate its efficacy by studying data on 136 alectinib treated crizotinib-refractory patients with CNS metastases - 60% of the overall study population. Of this group, 50 had measurable CNS disease at baseline.

In the latter group, the objective response rate (ORR) at a median follow-up of 12.4 months was 64.0%, the CNS disease control rate was 90% and the median CNS duration of response was 10.8 months.

When all 136 patients were included, the corresponding ORR was 42.6%, the CNS disease control rate was 85.3% and the median CNS duration of response was 11.1 months. In the 95 patients with prior radiotherapy, the ORR was 35.8% and for those who had not had radiotherapy, it was 58.5%.

The CNS responses, with an overall duration of about 11 months, the investigators observe, "were comparable to those observed for the overall systemic disease assessment."

The authors also note that the drug's safety profile in the combined analysis "was consistent with previous studies confirming that alectinib is well tolerated in patients with or without baseline CNS metastases."

There were low rates of dose reductions (14.7%) and withdrawals (5.9%).

The investigators conclude by pointing out, "Two ongoing phase III, head-to-head studies are comparing the systemic and CNS efficacy of alectinib versus crizotinib for patients with ALK-positive NSCLC who are ALK inhibitor naive."

Dr. Camidge has relationships with Genentech. Other authors have relationships with Genentech and other drug companies and a three are employees of Hoffman-La Roche who provided third-party medical writing support.