Better Results in NSCLC with Higher Dose of ALK Inhibitor

Doubling the dose of the ALK inhibitor Alunbrig (brigatinib) improved outcomes in patients with Xalkori (crizotinib)-refractory non-small cell lung cancer (NSCLC), according to a recent study published in the Journal of Clinical Oncology.

About ALK + NSCLC

Lung cancer is the leading cause of cancer death in the U.S. and around the world, highlighting the importance of developing effective new approaches to treatment. Up to 7 percent of non-small cell lung cancers (NSCLC) have an abnormal version of the anaplastic lymphoma kinase (ALK) gene. Lung cancers with this abnormality typically occur in non-smokers. The abnormal gene contributes to the growth and development of cancer cells. Xalkori is another ALK-inhibitor used to treat NSCLC, but most patients will become resistant to it.

In the current study patients who started treatment at 90 mg/day and had their dose gradually increased to 180 mg/day experienced an improved response rate (54% versus 45%) and this translated into a delay in cancer progression and prolonged survival. Importantly these better outcomes occurred with limited additional side effects.

Determining the most effective dose of a new medication requires significant work in large numbers of cancer patients.  In fact, many new cancer medications may be initially approved by the Food and Drug Administration at a dose which is effective, but not necessarily optimal.  Higher doses of chemotherapy drugs oftern kill more cancer cells than lower doses. When higher doses of therapy kill more cancer than lower doses, doctors say there is a “dose response effect.”  Additional post FDA approval clinical trials are performed to refine dosing regimens and drug combinations.

Reference: http://ascopubs.org/doi/full/10.1200/JCO.2016.71.5904

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