Quality of Life Improvement With Docetaxel Plus Plinabulin Versus Pegfilgrastim

Preliminary data from the phase 2/3 multicenter, randomized, double-blind Protective-1 study show that intravenous plinabulin (BPI-2358), meant to prevent chemotherapy-induced neutropenia (CIN), significantly improved quality of life (QOL), compared with pegfilgrastim (Neulasta), when taken with docetaxel for treatment of non—small cell lung cancer (NSCLC). The small molecule from BeyondSpring is currently in late-stage clinical development.¹

CIN in patients undergoing treatment for cancer involves the destruction of neutrophils, “a patient’s first line of defense against infections.” The usual treatment calls for granulocyte-colony stimulating factor monotherapy, of which pegfilgrastim is one. However, this has been shown to lead to grade 3/4 neutropenia, which can affect chemotherapy.²

In phase 2 of the current study, patients were assigned to docetaxel 75 mg/m² plus 1 of 3 doses of plinabulin—5 mg/m² (n = 14), 10 mg/m² (n = 13), or 20 mg/m² (n = 14)—on day 1 or docetaxel 75 mg/m² on day 1 and pegfilgrastim 6 mg on day 2. The plinabulin was administered 30 minutes after the docetaxel. The patients were evaluated before treatment on day 1 for 4 treatment cycles using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), across 3 categories: global health status/QOL, functional scales, and symptom scales. Scores were also summarized.¹

The 20-mg/m² dose of plinabulin, which is the clinically effective dose for CIN, significantly improved QOL for the following measures¹:

• Global health status (P <.0001)
• Symptom scale (P <.009)
• Summary score (P <.02)
• Fatigue (P <.03)
• Pain (P <.03)
• Insomnia (P <.05)

“While this analysis is exploratory, these preliminary results are statistically and clinically significant and indicate improvements with plinabulin in the QOL for patients being treated with docetaxel for advanced non-small cell lung cancer in addition to protecting against CIN,” stated Douglas Blayney, MD, global principal investigator for BeyondSpring’s CIN development program and professor of medicine at the Stanford University School of Medicine.

Plinabulin works by binding to and essentially disrupting the protein tubulin, which forms microtubules within cells, affecting different cells in various ways. This activates the GEF-H1 protein, which spurs dendritic cells to activate T cells, enabling plinabulin to shrink tumors and increase survival. Data also indicate that plinabulin boosts production of primitive stem/progenitor cells in bone marrow, which produce mature immune cells.³

Plinabulin is currently in late-stage clinical development in NSCLC and for prevention of CIN.

Reference

1. Blayney D, Mitchell D, Lelorier Y, Huang L, Mohanlal RW. Quality of Life in NSCLC patients treated with docetaxel and either plinabulin or pegfilgrastim for prevention of neutropenia. Presented at: 2019 World Conference on Lung Cancer; September 7-10, 2019; Barcelona, Spain. Poster P1.01. bit.ly/2Rn3FZw. Accessed January 16, 2020.

2. BeyondSpring’s plinabulin demonstrates superior quality of life over pegfilgrastim in a head-to-head comparison trial for the prevention of neutropenia [news release]. New York, NY: Globe Newswire; August 23, 2019. bit.ly/30uDIeJ. Accessed January 16, 2020.

3. Plinabulin: overview. BeyondSpring website. beyondspringpharma.com/ChannelPage/index.aspx. Accessed January 16, 2020.