Plinabulin Reduces Duration of Severe Neutropenia in Patients With NSCLC
Findings from 3 studies show that treatment with plinabulin elicits efficacy and reduces the duration of severe neutropenia in patients with non–small cell lung cancer receiving docetaxel.
Multiple analyses of plinabulin monotherapy support the efficacy of the agent in reducing the mean duration of severe neutropenia (DSN) for patients with non–small cell lung cancer (NSCLC) who are receiving docetaxel, according to BeyondSpring, Inc.1
Analyses of the agent were presented at 3 medical conferences and include the phase 2 study 101 (NCT00630110) and phase 3 DUBLIN-3 study (NCT02504489), which are trials of plinabulin plus docetaxel vs docetaxel alone in patients receiving second- and third-line therapy for NSCLC, and study 105, the PROTECTIVE-1 trial (NCT03102606), which is a phase 2/3 trial of plinabulin vs pegfilgrastim (Neulasta) with docetaxel in patients with NSCLC, breast cancer, and prostate cancer.
“Docetaxel-induced neutropenia can cause life-threatening infections in cancer patients, and the current standard of care, prophylactic treatment with a G-CSF [granulocyte colony stimulating factor] in high-risk patients, has limitations. It has to be administered 24 hours following chemotherapy, and patients can experience post-treatment bone pain, a mild reduction in platelet count and a decline in quality of life,” said Douglas Blayney, MD, professor of medicine emeritus at Stanford University Medical School and global principal investigator for the plinabulin neutropenia prevention studies, in the press release.
In the first 2 randomized NSCLC trials, studies 101 and 103, results of docetaxel-induced neutropenia were compared between the plinabulin arm and the control arm. DSN was calculated based on day 8 absolute neutrophil count (ANC) values in the plinabulin and control arms. Recent data from these trials were presented at the 2022 American Society of Hematology Annual Meeting.
Patients with NSCLC were administered either docetaxel at 75 mg/m2 and plinabulin or placebo as control in studies 101 and DUBLIN-3. Patient characteristics were comparable between the experimental and control arms of the studies. Neutropenia was most prevalent in cycle 1.
In both of these independent randomized studies, treatment with plinabulin led to a reduction in grade 4 neutropenia, grade 3/4 neutropenia, any-grade neutropenia, and DSN compared with those given the placebo for docetaxel-induced neutropenia.2 These results show that same-day dosing and avoidance of neutropenia with plinabulin are expected to minimize adverse events in patients with NSCLC who are receiving docetaxel.
Data presented at the European Society for Medical Oncology Asia Congress 2022 also showed plinabulin to be superior for the prevention of docetaxel-induced neutropenia and hematologic complications compared with patients in the control arm based on a non-randomized comparison of the plinabulin group from the PROTECTIVE-1 trial and the control group from the DUBLIN-3 study.
Regarding safety, grade 4 neutropenia was observed in 17% of patients given plinabulin vs 40% given placebo (P = .02).1 The mean DSN was 0.43 days for those administered plinabulin vs 1.32 days with placebo (P = .002) and plinabulin demonstrated a favorable quality of life and safety profile.
Then, data for plinabulin from the PROTECTIVE-1 trial vs control data (placebo or no treatment) were presented at the 2022 San Antonio Breast Cancer Symposium. In a presentation of the data, the end point of hematologic complications in 27 patients with early breast cancer was compared with the no-treatment studies in which patients were administered docetaxel at 75 mg/m2 without G-CSF. Patients were required to have had 1 or more NCCN (National Comprehensive Cancer Network) high febrile neutropenia risk factors.
Findings showed that in the no-treatment studies, blood sampling was infrequent and likely underestimated grade 4 neutropenia frequency. While there was a higher frequency of ANC sampling in cycle 1 of the trial, plinabulin was also superior in this study compared with no-treatment for docetaxel-induced neutropenia and hematologic complications.
Furthermore, the quality of life was maintained. Looking at safety, minimal adverse events were seen and included minimal bone pain burden in the plinabulin arm vs control arm.
“The data that we presented at these 3 conferences demonstrate that plinabulin can provide solutions for some of the challenges seen with G-CSF. Plinabulin is given on the same day as chemotherapy as a short infusion, has minimal associated bone pain, no reduction in platelet count and quality of life is maintained throughout the course of therapy. Importantly, the analyses showed a reduction in mean DSN of 1 day or more in NSCLC patients receiving plinabulin vs placebo [no G-CSF], which is the gold standard for regulatory review,” added Blayney.
