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Original Investigation
September 24, 2020

Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia in Adults With Non–Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial

Author Affiliations
  • 1Stanford Cancer Institute, Stanford, California
  • 2Harbin Medical University Cancer Hospital, Harbin, China
  • 3Department of Medical Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China
  • 4Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
  • 5Dnipropetrovsk Medical Academy, Ukraine. Dnepropetrovsk, Ukraine
  • 6Sumy Regional Clinical Oncology Dispensary, Sumy State University, Sumy, Ukraine
  • 7Volgograd Regional Clinical Oncology Dispensary, Volgograd, Russia
  • 8Mid Florida Hematology and Oncology Center, Orange City
  • 9Redlands Community Hospital, Redlands, California
  • 10SBI of Healthcare Oncology Dispensary No. 2, Ministry of Health of Krasnodar Region, Sochi, Russia
  • 11BeyondSpring Pharmaceuticals, New York, New York
  • 12Statogen Consulting, Wake Forest, North Carolina
  • 13Anoixis Corporation, Natick, Massachusetts
  • 14Wanchun Bulin Pharmaceuticals Limited, Dalian, China
  • 15Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  • 16Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China
JAMA Oncol. 2020;6(11):e204429. doi:10.1001/jamaoncol.2020.4429
Key Points

Question  What is the recommended phase 3 dose of the non–granulocyte colony-stimulating factor small molecule plinabulin for prevention of chemotherapy-induced neutropenia in adults with non–small lung cancer (NSCLC)?

Findings  This randomized phase 2 clinical trial of 55 patients with NSCLC compared 3 plinabulin doses (5, 10, and 20 mg/m2) with pegfilgrastim 6 mg in patients receiving intermediate febrile-neutropenia risk chemotherapy. The plinabulin 40-mg fixed dose, which is equivalent to the 20 mg/m2 dose, given on the same day as chemotherapy had the same duration of days of severe neutropenia as pegfilgrastim, the current standard of care.

Meaning  This study found that fixed-dose plinabulin was noninferior to pegfilgrastim in duration of severe neutropenia and will be compared with pegfilgrastim in a phase 3 trial of patients with NSCLC to confirm these results.

Abstract

Importance  Plinabulin is a novel, non–granulocyte colony-stimulating factor (GCSF) small molecule with both anticancer and neutropenia-prevention effects.

Objective  To assess the efficacy and safety of plinabulin compared with pegfilgrastim for the prevention of chemotherapy-induced neutropenia following docetaxel chemotherapy in patients with non–small lung cancer.

Design, Setting, and Participants  This was a randomized, open-label, phase 2 clinical trial of 4 treatment arms that was conducted in 19 cancer treatment centers in the United States, China, Russia, and Ukraine. Participants were adult patients with non–small cell lung cancer whose cancer had progressed after platinum-based chemotherapy. Data were collected from April 2017 through March 2018 and analyzed from August 2019 through February 2020.

Interventions  All patients received docetaxel 75 mg/m2 on day 1 and were randomly assigned to 1 of 3 doses of plinabulin (5, 10, or 20 mg/m2) on day 1 or to pegfilgrastim 6 mg on day 2. Patients were treated every 21 days for 4 chemotherapy cycles.

Main Outcomes and Measures  The primary end point was the determination of the recommended phase 3 dose of plinabulin based on the days of severe neutropenia during chemotherapy cycle 1. Daily complete blood cell counts and absolute neutrophil counts were drawn during times of anticipated neutropenia during cycle 1.

Results  Of the 55 patients randomized and evaluated, the mean (SD) age was 61.3 (10.2) years, and 38 (69.1%) were men. With each escalation of the plinabulin dose, the incidence of any grade of neutropenia decreased. There were no significant differences in mean (SD) days of severe neutropenia among those treated with pegfilgrastim (0.15 [0.38] days) when dosed at day 2 vs plinabulin 20 mg/m2 (0.36 [0.93] days; P = .76) when dosed at day 1, and no safety signals were detected.

Conclusions and Relevance  Single dose-per-cycle plinabulin has a similar neutropenia protection benefit as pegfilgrastim. Plinabulin 40 mg fixed dose, which is pharmacologically equivalent to 20 mg/m2, will be compared with pegfilgrastim 6 mg in the phase 3 portion of this trial. Noninferior days of severe neutropenia will be the primary end point, and bone pain reduction, thrombocytopenia reduction, and quality of life maintenance will be secondary end points.

Trial Registration  ClinicalTrials.gov Identifier: NCT03102606

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