The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.
Key Takeaways
-
The combination of plinabulin and pegfilgrastim was superior to pegfilgrastim alone in preventing chemotherapy-induced neutropenia (CIN) in patients with stage I, II, or III breast cancer after receiving three-drug TAC (docetaxel, doxorubicin, cyclophosphamide) chemotherapy.
-
Phase 3 studies will assess the combination of plinabulin 40 mg and pegfilgrastim 6 mg to reduce febrile neutropenia and other parameters in patients with early-stage breast cancer.
Why This Matters
-
CIN causes infection-related complications, including sepsis, unplanned hospitalizations, and death. More complete CIN protection is an unmet medical need.
-
While pegfilgrastim is myeloprotective in the second week of the chemotherapy cycle and plinabulin has been shown to mitigate severe neutropenia with docetaxel chemotherapy in the first week, the combination shows promise for enhanced CIN protection.
Study Design
-
This was a randomized, open-label phase 2 trial of 115 participants divided into two cohorts. All participants received four cycles of TAC chemotherapy.
-
The monotherapy cohort (42 patients) received pegfilgrastim 6 mg on day 2. The combined-therapy cohort (51 patients) received plinabulin 20 mg/m2 on day 1 and pegfilgrastim 1.5, 3, or 6 mg on day 2.
-
The primary objective was to establish the recommended phase 3 dose of plinabulin, based on pharmacokinetic and pharmacodynamic analyses.
-
The primary efficacy endpoint was duration of severe neutropenia. Secondary endpoints included frequency of patients with at least 1 day of grade 4 neutropenia, grade 3 or 4 neutropenia, absolute neutrophil count nadir, changes in bone pain, and relative dose intensity.
-
Participants were accrued between December 2017 and January 2019 at nine sites in China and Ukraine.
Key Results
-
The study established the recommended phase 3 dose of plinabulin 40 mg and pegfilgrastim 6 mg in combination over pegfilgrastim 6 mg alone in early-stage breast cancer patients treated with TAC
-
The mean duration of severe neutropenia of combination therapy was 0.69 days, vs 0.73 days for pegfilgrastim alone.
-
A total of 37.5% of patients receiving combination therapy had at least 1 day of grade 4 neutropenia, vs 59.1% for patients receiving pegfilgrastim alone.
-
Combination therapy was associated with fewer days of bone pain than pegfilgrastim alone.
-
All patients receiving combination therapy were able to receive >85% of the planned chemotherapy dose. Only 82% in the monotherapy arm were able to receive >85% of therapy.
-
The relative dose intensity also favored the combination arm, as fewer patients (6.25%) had their chemotherapy regimens modified compared with those on monotherapy (14.29%).
Limitations
-
Small sample sizes in each arm may have led to inaccurate duration of severe neutropenia. In this study, the incidence of grade 4 neutropenia was 59.1%, whereas in larger studies, it has been reported to be 83% to 93%.
-
When less than 2 days, the duration of severe neutropenia likely has less predictive value for clinically relevant endpoints such as febrile neutropenia, hospitalization, and death.
-
The absence of blinding may have affected subjective measures like bone pain.
Study Disclosures
-
The study was funded by BeyondSpring Pharmaceuticals, Inc.
-
Blayney reports receiving grants to his institution from BeyondSpring Pharmaceuticals, Inc, owns stock in Madora and Artelo Biosciences, and receives consulting fees from Diaichi, Embold Health, Ipsen, Tersera, and Lilly.
-
Huang reports being an employee and stockholder of BeyondSpring Pharmaceuticals, Inc.
-
Mohanlal reports being an employee and stockholder of BeyondSpring Pharmaceuticals, Inc.
-
Du is an employee of Anoxis Corporation.
-
Ogenstad is an employee of Statogen Consulting.
This is a summary of the preprint research study, “Plinabulin and Pegfilgrastim in Combination for the Prevention of Chemotherapy-Induced Neutropenia in Patients with Breast cancer (PROTECTIVE-2): A Randomized Trial,” published January 4 on ResearchSquare.com. It was led by Douglas W. Blayney, MD, of Stanford Cancer Center. This preprint summary is provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.
For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.
Source: Read Full Article