Docetaxel is approved for use in patients with non–small-cell lung cancer (NSCLC) after the failure of first-line chemotherapy. The treatment, however, has an unfavorable toxicity profile that limits its use. An investigational therapy, plinabulin (BeyondSpring Pharmaceuticals), is being developed in combination with docetaxel to provide a regimen with an improved safety profile. Plinabulin is a first-in-class small-molecule vascular-disruptive agent with immuno-oncology effects.
A phase 2 study compared the safety and efficacy of the plinabulin/docetaxel combination (n = 90) with that of docetaxel alone (n = 73) in patients with NSCLC entering second- or third-line therapy. Plinabulin was administered intravenously at 20 mg/m2 (n = 40) or 30 mg/m2 (n = 50), and docetaxel was administered at 75 mg/m2 (n = 73).
Efficacy results from this study were presented at the 2014 annual meeting of the American Society of Clinical Oncology (ASCO). The plinabulin/docetaxel combination provided a significant duration-of-response benefit over docetaxel alone (12.7 months vs. 1.5 months, respectively; P < 0.05).
The investigators are now preparing to present safety results for the plinabulin/docetaxel combination at the next ASCO meeting, to be held on June 3–7 in Chicago.
In the phase 2 study, the combination treatment mitigated some of the toxicities of docetaxel monotherapy. Plinabulin/docetaxel provided significant (P < 0.01) reductions in grade-3 or grade-4 neutropenia (7% vs. 25%) and in asthenia (13% vs. 28%); significantly reduced the use of granulocyte-colony stimulating factor (G-CSF) (14% vs. 29%); and significantly reduced docetaxel dose reductions due to toxicity (6% vs. 20%). The neutropenia benefit was likely due to the plinabulin-induced release of cytokines, such as interleukin-1 (IL-1) and IL-6, which are known to increase the neutrophil count.
A global phase 3 study of the plinabulin/docetaxel combination compared with docetaxel alone is currently under way in the United States, China, Australia, and New Zealand.
Plinabulin is administered by a 30-minute intravenous infusion. It is given 60 minutes after the completion of a docetaxel infusion.