"This approach provides potential benefits for both clinicians and patients: clinicians may gain greater control over cancer care, and patients may experience better clinical outcomes and an improved quality of life."
Combining plinabulin with pegfilgrastim (Neulasta) may allow more patients with chemotherapy-induced neutropenia (CIN) to receive the optimal dose and regimen of chemotherapy, potentially leading to better outcomes overall, according to findings from the phase 2 PROTECTIVE-2 trial, BeyondSpring, Inc. announced in a press release.
“Clinical research demonstrates that patients who receive over 85 percent of the optimal chemotherapy dose on time have significantly better overall survival,” said Dr. Lan Huang, chief executive officer and co-founder, BeyondSpring, in a statement. "Additionally, monotherapy G-CSF has been shown to help some patients maintain chemotherapy regimens. However, in an analysis of over 16,000 patients with monotherapy G-CSF, very few patients are able to maintain their targeted regimen. It is clear that oncologists and patients need more tools to stay the course for improved survival.”
In the study, dose reduction was over 15%, but only 6.3% were from the plinabulin plus pegfilgrastim arm compared with pegfilgrastim monotherapy, in which dose reductions were required in 22.7% of patients. This represents a 72% improvement and a 50% survival reduction.
The chemotherapy regimens used in the study were docetaxel, doxorubicin, and cyclophosphamide (TAC) and taxotere plus cyclophosphamide (TC). Notably, there were no patients in the plinabulin plus pegfilgrastim arm who required a downgrade from the TAC regimen to the TC regimen, compared with the pegfilgrastim monotherapy arm, in which 18.2% of patients downgraded to TC. The difference was P <.05. This is notable because prior research showed that TAC had an overall response rate (ORR) of 83%, which is superior to the TC regimen, which had an ORR of 42%.
“Having the ability to greatly reduce grade 4 neutropenia means that oncologists can optimize cancer patients’ chemotherapy regimens, turning the 4Ds into the 4Ss: stable doses, sustained cycles and the strongest regimens, allowing patients to stay the course,” Ramon Mohanlal, chief medical officer and executive vice president, Research and Development, BeyondSpring stated.
PROTECTIVE-2 is an ongoing study designed to assess the safety and efficacy of plinabulin/pegfilgrastim versus pegfilgrastim alone in patients with breast cancer to prevent severe neutropenia in patients receiving myelosuppressive TAC. The study is evaluating the percentage of patients with duration of severe neutropenia (DSN) as the primary end point. The secondary end points included mean DSN, mean area under the curve, the percentage of subjects without grade 3/4 neutropenia, mean DSN within 15 days, average change in bone pain, rate of composite risks, and the percentage of patients with relative dose intensity less than 85%.
Patients were required to be at least 18 years of age and eligible to receive 4 cycles of TAC chemotherapy, per the investigator’s opinion. Patients were also required to have pathologically confirmed cancer, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and satisfactory laboratory results.
Plinabulin is a marine-derived small molecule and is a colony stimulating factor. The addition of plinabulin was hypothesized to improve outcomes in oncology patients with CIN, based on prior data indicating that plinabulin boosted the number of hematopoietic stem and progenitor cells in mice.
“This approach provides potential benefits for both clinicians and patients: clinicians may gain greater control over cancer care, and patients may experience better clinical outcomes and an improved quality of life. The improvement in the prevention of grade 4 neutropenia that is seen with the plinabulin/ pegfilgrastim combination is even more important in today’s healthcare environment due to the devastating impact of COVID-19 on immune-suppressed patients. We look forward to the upcoming phase 3 interim topline data readout for PROTECTIVE-2, which represents an important milestone to potentially serve as a new standard of care in CIN treatment,” Mohanlal stated.
BeyondSpring's PROTECTIVE-2 (Study 106) phase 2 trial for chemotherapy-induced neutropenia shows positive results in chemotherapy optimization with potentially better clinical outcomes. News release. BeyondSpring, Inc. June 9, 2020. Accessed June 10, 2020. https://bit.ly/3dTdt7x.