This study found that single dose-per-cycle plinabulin has a similar neutropenia protection benefit as pegfilgrastim among adult patients with non-small cell lung cancer.
A randomized, open-label, phase 2 clinical trial published in JAMA Oncology indicated that single dose-per-cycle plinabulin has a similar neutropenia protection benefit as pegfilgrastim (Neulasta) among adult patients with non-small cell lung cancer (NSCLC).
“The [pharmacokinetic and pharmacodynamic; PK/PD] analysis confirms the recommended phase 3 dose and also shows that a plinabulin 40-mg fixed-dose is equivalent to the plinabulin 20-mg/m2 dose,” the authors wrote.
This trial of 4 treatment arms was conducted in 19 cancer treatment centers in the US, China, Russia, and Ukraine. The study included 55 adult patients with NSCLC whose cancer had progressed after platinum-based chemotherapy.
Each of the participants received a 75 mg/m2 dose of docetaxel on day 1 and were then randomly assigned to receive a 5, 10, or 20 mg/m2 dose of plinabulin on day 1 or a 6 mg dose of pegfilgrastim on day 2. Patients were treated every 21 days for 4 cycles of chemotherapy.
The primary end point of the study was the determination of the recommended phase 3 dose of plinabulin based on the days of severe neutropenia during chemotherapy cycle 1. Of note, daily complete blood cell counts and absolute neutrophil counts were drawn during times when neutropenia was expected during cycle 1.
The incidence of any grade of neutropenia was found to decrease with each escalation of the plinabulin dose. Further, there was no significant difference observed in mean (SD) days of severe neutropenia among patients treated with pegfilgrastim (0.15 [0.38] days) when dosed at day 2 versus 20 mg/m2 of plinabulin (0.36 [0.93] days; P = .76) when dosed at day 1, and no safety signals were detected.
“In patients who had no bone pain at study entry, there was no bone pain after day 3 in the plinabulin 20 mg/m2 arm, while 35% of patients in the pegfilgrastim arm reported bone pain,” the authors noted. “Patients in all plinabulin arms also experienced less thrombocytopenia than patients receiving pegfilgrastim, with no patient experiencing any grade of thrombocytopenia.”
Given these results, a 40 mg fixed day 1 dose of plinabulin will be compared with a 6 mg dose of pegfilgrastim in the phase 3 portion of this trial moving forward. The primary end point for this portion of the study will be noninferior days of severe neutropenia. Key secondary end points from the phase 3 study will include bone pain reduction, thrombocytopenia reduction, and maintenance or improvement in quality of life.
In addition, a separate anticancer program will be investigating the anticancer efficacy of plinabulin and should address concerns that plinabulin may have a harmful effect on chemotherapy efficacy.
“If successful, we hope to demonstrate that plinabulin has efficacy comparable with pegfilgrastim for [chemotherapy-induced neutropenia] prevention but has more convenient dosing, superior safety and quality of life, has less associated bone pain, and less associated thrombocytopenia,” the authors explained. “Single-agent plinabulin, given the same day as chemotherapy, may fill the need for primary [febrile neutropenia] prophylaxis in patients receiving chemotherapy regimens with 10% to 20% [febrile neutropenia] risk, for which current guidelines do not recommend primary [granulocyte colony-stimulating factor; G-CSF] prophylaxis.”
Blayney DW, Zhang Q, Feng J, et al. Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia in Adults With Non-Small Cell Lung Cancer. JAMA Oncology. doi: 10.1001/jamaoncol.2020.4429