Utilizing Next-Generation ALK Inhibitors in NSCLC

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There are currently more than 10 next-generation ALK inhibitors in development as potential treatments for patients with non-small cell lung cancer (NSCLC). These newer agents appear to penetrate the CNS and are safe and effective in patients with crizotinib-resistant disease, notes Ramaswamy Govindan, MD.

The next challenge facing these treatments will be the discovery of an optimal sequence, Govindan suggests. The future for patients with ALK-positive NSCLC could reflect a similar landscape as chronic myelogenous leukemia (CML), which has several TKIs targeted against the BCR-ABL gene fusion, Govindan believes.

Many of the next generation agents in development have shown promising activity in patients with CNS metastases. However, at this point, pharmacokinetic data on the penetration of these drugs into the brain is mostly from preclinical studies, notes D. Ross Camidge, MD, PhD. Despite this, evidence of these agents efficacy in patients with CNS metastases has been demonstrated by high response rates in phase I/II studies.

With the wealth of highly effective therapies in development, the next emphasis will be side effect management. In the clinical trials leading to its approval, ceritinib was associated with high levels of GI toxicity. However, to help ameliorate some of these side effects, clinical trials are beginning to look at the effects of food intake on absorption, Alice T. Shaw, MD, PhD, notes. At this time, it appears that taking ceritinib following a meal or snack could help ease some of the side effects of the drug.