Alectinib in crizotinib-resistant lung cancer – Is it safe and effective?

This trial looked at the safety and efficacy of alectinib (Alecensa) in the treatment of patients with ALK-rearranged non-small cell lung cancer (NSCLC) that had progressed after treatment with crizotinib (Xalkori).

This trial concluded that alectinib was safe and effective in these patients.

Some NSCLCs are associated with a rearrangement, or switching, of the anaplastic lymphoma kinase (ALK) gene with another gene. Crizotinib is a drug used to treat ALK-rearranged NSCLC that can lead to longer survival rates than chemotherapy. Many patients, though, progress despite crizotinib treatment. This progressive disease is resistant to crizotinib and commonly spreads (metastasizes) to the central nervous system (CNS). 

Alectinib is a treatment that blocks the activity of ALK. Alectinib was effective against NSCLC that spread to the CNS in studies done in animals. Alectinib was recently approved by the US Food and Drug Administration (FDA) for use in patients who have become resistant to crizotinib.

This trial examined the safety and effectiveness of alectinib in patients with ALK-rearranged NSCLC that progressed following crizotinib treatment. The trial evaluated 122 patients. 84 of these patients presented with CNS metastases. Patients were treated with 600 mg alectinib twice per day. Patients were followed for an average of 30 weeks. The objective response rate (ORR, patients with tumors that decrease by at least 50%) and the disease control rate (DCR, patients with tumors that shrink or remain the same size) were measured.

The overall ORR of the 122 patients evaluated was 50%, the DCR was 79% and the average progression free survival time (time from treatment until disease progression) was 8.9 months.

Of the 84 patients with CNS tumors, the ORR was 57% and the DCR was 83%.

Treatment related adverse effects included fatigue (14% of patients), muscular pain (17% of patients) and constipation (15% of patients). Only 1 patient died, due to treatment-related intestinal perforation (a hole in the wall of the intestine). 

The study concluded that alectinib is an effective and safe treatment for patients with crizotinib–resistant, ALK-rearranged NSCLC.

The study did not include any comparisons between alectinib and other ALK inihibitors, which needs to be tested to determine effectiveness.

This study was funded by Hoffmann-La Roche, the manufacturers of alectinib.

Discuss the use of ALK inhibitors with your physician.