Plinabulin noninferior to pegfilgrastim for chemotherapy-induced neutropenia prevention
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Plinabulin demonstrated similar efficacy to pegfilgrastim for the prevention of chemotherapy-induced neutropenia, according to results of a randomized phase 3 study published in JAMA Network Open.
“Plinabulin, a nongranulocyte colony-stimulating factor agent that has anticancer properties, was shown to reduce the incidence of chemotherapy-induced neutropenia in a phase 2 clinical trial including patients with lung cancer,” Douglas W. Blayney, MD, professor of medicine at Stanford Cancer Institute, told Healio. “We conducted a separate phase 2 clinical trial that had more frequent neutrophil monitoring and confirmed the plinabulin benefit. We then proceeded to this phase 3 study of single-agent plinabulin compared with single-agent pegfilgrastim.”
Methods
Blayney and colleagues sought to demonstrate noninferiority of plinabulin (BeyondSpring Pharmaceuticals) dosed at 40 mg plus placebo vs. pegfilgrastim (Neulasta, Amgen) dosed at 6 mg plus placebo for prevention of severe neutropenia among 105 patients (median age, 59 years; 65 women) with breast, prostate or non-small cell lung cancer receiving docetaxel across multiple centers in China, Russia, Ukraine and the U.S.
Day of severe neutropenia during cycle one served as the primary endpoint. Secondary endpoints included clinical consequences of chemotherapy-induced neutropenia — febrile neutropenia, hospitalizations, infections, antibiotic use and modifications of chemotherapy dose — as well as patient-reported outcomes for bone pain score, markers for immune suppression, immature neutrophils and safety.
Key findings
Results showed a noninferiority margin of 0.65 days, meeting the primary endpoint with a mean difference between the pegfilgrastim and plinabulin groups of 0.52 days (98.52% CI, 0.4-0.65). Researchers reported no significant difference in frequency of grade 4 neutropenia during cycle 1, and an earlier onset of action with plinabulin with less grade 4 neutropenia during the first week of cycle 1.
Patients assigned plinabulin (n = 52) experienced lower rates of febrile neutropenia (zero vs. 1.9%), infections (7.7% vs. 15.1%), chemotherapy dose delay of more than 7 days (3.8% vs. 5.7%) and permanent chemotherapy discontinuation (13.5% vs. 26.4%) compared with those assigned pegfilgrastim (n = 53).
Moreover, researchers observed significantly less bone pain (difference, 0.67; 95% CI, 1.17 to 0.16) and a better immunosuppressive profile (3.8% vs. 46%; P < .001) among patients assigned plinabulin vs. pegfilgrastim.
Because of the difficulty with patient travel and transportation of blood specimens to a central laboratory, the sponsor decided to halt the trial, Blayney noted.
“Plinabulin has clinical advantages as it can be given as one fixed dose on the same day as chemotherapy, without an onbody injector or a return to the infusion center for one or more injections in contradistinction to pegfilgrastim or filgrastim. Plinabulin may have less bone pain than pegfilgrastim and may not be as immunosuppressive,” Blayney said.
Implications
“Though the evidence was convincing, the FDA was not convinced to approve marketing of plinabulin in the U.S. based on this and another phase 3 study using the combination of plinabulin and pegfilgrastim,” Blayney said. “The sponsor is now pursuing marketing in China. We have also completed phase 2 and phase 3 studies of the combination of plinabulin and pegfilgrastim in high-risk febrile neutropenia chemotherapy in patients with breast cancer. The reports of these studies are currently under review for publication.”
For more information:
Douglas W. Blayney, MD, can be reached at Stanford Cancer Institute, 875 Blake Wilbur Drive, Mail Code 5827, Stanford, CA 94305; email: dblayney@stanford.edu.
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