In the phase 3 PROTECTIVE-2 trial, patient with breast cancer who received plinabulin and pegfilgrastim experienced a reduction in the incidence of profound neutropenia that was 53% more effective than that of chemotherapy, according to findings presented during the 2020 San Antonio Breast Cancer Symposium.
In the phase 3 PROTECTIVE-2 trial (Study 106; NCT03294577), patient with breast cancer who received plinabulin and pegfilgrastim (Neulasta) experienced a reduction in the incidence of profound neutropenia (CIN) that was 53% more effective than that of chemotherapy, according to findings presented during the 2020 San Antonio Breast Cancer Symposium.1
Results showed that the incidence of profound neutropenia was 21.6% with the combination vs 46.4% with pegfilgrastim alone (P = .0001) in patients with breast cancer who were undergoing chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC). Moreover, plinabulin/pegfilgrastim also reduced the risk of febrile neutropenia by 41% compared with pegfilgrastim alone, based on a reduction of profound neutropenia.
There was also a 50% reduction in the mean duration of profound neutropenia with the combination at 0.3 days compared with 0.6 days with pegfilgrastim alone (P = .0004).
“It is clinically meaningful to reduce [febrile neutropenia] risk by 41% in the combination, compared to pegfilgrastim alone, which is the only major breakthrough advancement in CIN prevention in the last 30 years. The CIN protection from plinabulin added to pegfilgrastim, particularly in the first week of chemotherapy when 75% of CIN-related complications occur before the effect of pegfilgrastim kicks-in in week 2, fills the treatment gap in current standard of care,” said principal investigator Douglas Blayney, MD, professor of medicine at Stanford Cancer Center. “The combination of plinabulin with pegfilgrastim represents a major advancement in offering protection against CIN, with the potential to reduce [febrile neutropenia] risk, in the care of cancer patients.”
In September 2020, the FDA granted a breakthrough therapy designation to the combination of plinabulin, which is a differentiated immune and stem cell modulator, in combination with pegfilgrastim for the treatment for patients with chemotherapy-induced neutropenia. The designation for plinabulin was based on clinical evidence from PROTECTIVE-2 trial and other CIN studies. China’s National Medical Products Administration also granted plinabulin breakthrough status in September 2020.
In the double-blind, active-controlled, international, phase 3 PROTECTIVE-2 study, 221 patients were randomized to receive docetaxel, doxorubicin, and cyclophosphamide (day 1 dose) in a 21-day cycle along with 40 mg of plinabulin (day 1 dose) and 6 mg pegfilgrastim (day 2 dose; n = 111) versus a single 6-mg dose of pegfilgrastim (day 2 dose; n = 110).
Prior reported results showed that pegfilgrastim also improved the following secondary end points: duration of severe neutropenia (DSN) cycle 1 on days 1 through 8 (absolute neutrophil count [ANC] <0.5 x 109 cells/L; P = .0065), DSN cycle 1 (P = .03); mean ANC nadir cycle 1 (P = .0002), and duration of profound neutropenia cycle 1 (ANC <0.1 x 109 cells/L; P = .0004).2
The full findings had reported that the improvement in preventing grade 4 chemotherapy-induced neutropenia (CIN) was statistically significant in cycle 1 at 31.5% with the combination versus 13.6% with pegfilgrastim alone (P = .0015), and key secondary end points were also met, including DSN cycle 1 D1 to 8, DSN cycle 1, and mean ANC nadir cycle 1.
Moreover, there was a lower frequency of grade 4 adverse events with the combination versus pegfilgrastim alone, at 58.6% and 80.0%, respectively.
In the phase 2 portion of the trial, the combination resulted in a reduction in CIN compared with pegfilgrastim monotherapy in patients who received TAC chemotherapy.3 Here, rates of grade 3 neutropenia were 81% vs 50% in the control and investigational arms, respectively (P < .05). Lower rates of grade 4 neutropenia were also observed in the combination arm compared with the monotherapy arm, at 38% vs 57%, respectively.
Moreover, patients who received treatment with the plinabulin combination experienced less bone pain compared with those who received single-agent pegfilgrastim. Bone pain for day 1 or longer was reported in 6% of those on the combination versus 95% of those on the monotherapy (P < .001). Rates of bone pain that persisted for 4 days or longer were 0% vs 33% in the investigational and control arms, respectively (P < .01).
The PROTECTIVE-2 results were further supported by other CIN studies that were conducted, data of which showed the early onset action of agent in week 1 with regard to neutrophil protection in various cancer types and several chemotherapies.
1. Blayney DW, Huang L, Mohanlal R. Superior and clinically meaningful protection against profound neutropenia with the plinabulin/pegfilgrastim (Plin/Peg) combination versus peg in breast cancer patients receiving TAC chemotherapy: phase 3 results from Protective-2 (BPI-2358-106). Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual. Abstract PS13-53-01.
2. BeyondSpring announces positive topline results from its PROTECTIVE-2 phase 3 registrational trial of plinabulin in combination with pegfilgrastim for prevention of chemotherapy-induced neutropenia. News release. BeyondSpring Therapeutics. November 16, 2020. Accessed November 16, 2020. https://bit.ly/35BVosZ
3. BeyondSpring announces positive topline interim results from PROTECTIVE-2 (Study 106) phase 3 trial evaluating superiority of plinabulin in combination with Neulasta for chemotherapy-induced neutropenia prevention. News release. BeyondSpring Pharmaceuticals. June 15, 2020. Accessed September 10, 2020. https://bit.ly/3fval2d