Plinabulin and Pegfilgrastim in Combination for the Prevention of Chemotherapy-Induced Neutropenia in Patients with Breast Cancer (PROTECTIVE-2): A Randomized Trial

Abstract PurposePlinabulin is a non-granulocyte colony-stimulating factor (G-CSF) novel small molecule with both anticancer and myeloprotective effects. Single-agent plinabulin is myeloprotective in the first week of the chemotherapy cycle, and pegfilgrastim in the second week. We assessed the efficacy and safety of the combination of plinabulin and pegfilgrastim for the prevention of chemotherapy-induced neutropenia (CIN) following chemotherapy.MethodsThis randomized, open-label, Phase 2 trial enrolled patients with breast cancer. All received docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 on Day 1. In the combined therapy cohort, patients received plinabulin 20 mg/m2 on Day 1 and 1.5, 3, or 6 mg pegfilgrastim on Day 2. The primary objective was to establish the recommended Phase 3 dose (RP3D). Secondary endpoints included absolute neutrophil count (ANC) nadir, relative dose intensity (RDI), and incidence of adverse events including neutropenia and bone pain.ResultsIn total, 115 patients were randomized and evaluated. The combination therapy at the RP3D (plinabulin 20 mg/m2 and pegfilgrastim 6 mg) was well-tolerated and had superior CIN prevention in terms of Grade 4 and Grade 3/4 neutropenia frequency, absolute neutrophil count (ANC) nadir, higher relative dose intensity (RDI), less bone pain, and less toxicity burden when compared with pegfilgrastim 6 mg alone.ConclusionPlinabulin combined with pegfilgrastim at the RP3D (plinabulin 20 mg/m2 Day 1 and pegfilgrastim 6 mg Day 2) had more favorable efficacy, safety, and tolerability profiles and lower bone pain incidence than did pegfilgrastim alone.Trial information Clinical Trial Registration: ClinicalTrials.gov NCT04227990Date registered: January 14, 2020 Retrospectively registered

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Efficacy, safety, and cost-effectiveness (CE) analysis of pegfilgrastim (P) and lenograstim (L) in patients (pts) with nonmetastatic breast cancer (nmBC) receiving myelosuppressive chemotherapy (mCT).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e19620 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e19620-e19620

Author(s):

Anselmo Papa ◽

Luigi Rossi ◽

Federica Tomao ◽

Fabio Ricci ◽

Erika Giordani ◽

...

Keyword(s):

Breast Cancer ◽

Retrospective Study ◽

Cost Effectiveness ◽

Absolute Neutrophil Count ◽

Neutrophil Count ◽

Bone Pain ◽

Single Injection ◽

Numerical Rate Scale ◽

Myelosuppressive Chemotherapy ◽

The Cost

e19620 Background: Neutropenia (N) is common in pts who receive mCT. This retrospective study was conducted to determine efficacy, safety and cost of single injection of P (6 mg) compared with daily L (263 μg), in primary prophilaxis of N in pts affected by nmBC, who received mCT. Methods: 50 women (median age 54 years) underwent to median 6 (range 4–8) CT doses with antracyclines +/- taxanes. At every cycle, 28 pts received daily L (median 5 injections from day 5 to 9), while 22 pts received one dose of P on day 2. Absolute neutrophil count, incidence of G3/G4-N, bone pain (BP: Numerical Rate Scale >7) and CE analysis were evaluated. Results: In overall population (OP) incidence of G3-N and G4-N was 25% and 68%, respectively in L vs 22.7% and 41%, respectively in P; two cases (7%) of febrile N (FN) occurred in pts treated with L and three cases (13.6%) of FN in P. In 19 pts treated with FEC100 (10 pts L vs 9 pts P) we observed 0% of G3-N and 30% of G4-N in L while 33% of G3-N and 44% of G4-N in P. 31 pts received TAC/AC+T (18 pts L vs 13 pts P) with G3-N and G4-N 38.8% and 66.6%, respectively in L vs 15.3% and 30.7%, respectively in P. 18.2% of pts, who received P, had BP vs 35.7% in L. Reduction of CT doses was observed in 35.7% in L vs 41% in P. In Italy the cost of 1 injection of P was about 1489,00 euro compared with about 655,00 euro for 5 injections of L. Conclusions: In our experience, 1 injection of P was more effective and expensive than 5 daily administration of L to control N in OP and in particular in TAC/AC+T, while in FEC100, L was satisfactory with good CE profile. No difference about incidence of NF. Safety of P and L were similar with a lower incidence of BP in P.

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Efficacy and safety of PEG-rhG-CSF in primary and secondary prevention of chemotherapy-induced neutropenia.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e19051 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e19051-e19051

Author(s):

Jun Zhu ◽

Huiping Li ◽

Zhengfu Fan ◽

Yunong Gao ◽

Meifeng Tu ◽

...

Keyword(s):

Primary Prevention ◽

Secondary Prevention ◽

Absolute Neutrophil Count ◽

Neutrophil Count ◽

Bone Pain ◽

Malignant Tumors ◽

Gynecologic Oncology ◽

Efficacy And Safety ◽

Primary And Secondary Prevention ◽

Chemotherapy Induced Neutropenia

e19051 Background: This study was to evaluate the efficacy and safety of PEG-rhG-CSF (brand name:jinyouli) in primary and secondary prevention of CIN(chemotherapy-induced neutropenia). Methods: This is a single-center,one-arm clinical study.Patients with non-myeloid malignant tumors were enrolled. PEG-rhG-CSF was given subcutaneously at 24-48h after chemotherapy. The indicator was febrile neutropenia(FN) and IV grade absolute neutrophil count. Results: From January 2016 until June 2018,217 patients were enrolled including 119 lymphoma patients, 50 breast cancer patients, 30 bone tumor patients,18 gynecologic oncology patients, and While146 with primary prevention and 71 with secondary prevention. The incidence of FN was 5.0% (35/692), which was 4.3% (21/478) in the primary prevention patients and 6.5% (14/214) in the secondary prevention patients ( p= 0.233).Logistic regression analysis showed that the longer the treatment cycle, the lower the incidence of FN. Comparison of the indicators of different chemotherapy cycles showed that the IV grade absolute neutrophil count (ANC) reduction was significantly lower in the primary prevention patients than in the secondary prevention patients in the first cycle of chemotherapy[17.1%(25/146) vs.46.5%(33/70),p = 0.000],the incidence of FN and IV grade ANC reduction were significantly lower in the second cycle of treatment than in the first cycle(p < 0.05).The adverse event were mainly bone pain, the incidence of 1/2 grade bone pain was 3.7% (8/217) and the incidence of grade 3/4 bone pain was 1.8% (4/217). Conclusions: The prevention of CIN with PEG-rhG-CSF after chemotherapy can effectively reduce the incidence of FN.For the first chemotherapy cycle, primary prevention is more effective than secondary prevention in preventing the incidence of IV grade ANC reduction. Clinical trial information: NCT02905916.

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Same day administration of pegfilgrastim with dose dense doxorubicin in early breast cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.671 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 671-671

Author(s):

K. T. Vance ◽

J. Carpenter

Keyword(s):

Breast Cancer ◽

Febrile Neutropenia ◽

Cancer Patients ◽

Early Breast Cancer ◽

Absolute Neutrophil Count ◽

Neutrophil Count ◽

Bone Pain ◽

Common Side Effect ◽

Breast Cancer Patients ◽

Dose Dense

671 Background: Pegfilgrastim is indicated to decrease the incidence of febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. In licensing studies, patients received a single dose of pegfilgrastim on day 2 of each chemotherapy cycle, which added an extra visit for day 2 administration. We administered pegfilgrastim to a series of early breast cancer patients on the same day of chemotherapy. We reviewed charts retrospectively to assess both efficacy and safety. Methods: Data on blood counts, toxicity and chemotherapy dosing was collected from July 1, 2003 to May 6, 2005 for all patients with early breast cancer who received sequential or combination doxorubicin, cyclophosphamide and paclitaxel on a 14 day schedule. Herceptin was given with paclitaxel and/or cyclophosphamide in 2 patients. Results: 64 patients with a median age of 50 years (range 22–67 years) were treated. 14 patients had stage I disease, 39 stage II and 11 stage III disease. Forty-one patients were treated postoperatively and 23 preoperatively. 211 cycles of doxorubicin were administered. After administration of doxorubicin, pegfilgrastim 6 mg s.c. was given on the same day. The lowest absolute neutrophil count on day 14 after doxorubicin was 1693/mm3 with no episodes of febrile neutropenia. The highest absolute neutrophil count was 23,671/mm3. The only dose reductions were five doxorubicin doses for grade 1–2 mucositis. Grade 1–2 nausea and vomiting was the most common toxicity seen after doxorubicin. Grade 1 bone pain was the most common side effect seen after pegfilgrastim occurring in 13/64 patients. There was no grade 3 or 4 toxicity of any kind. Conclusion: Pegfilgrastim administered on the same day as doxorubicin on a 14 day schedule was both safe and effective. Side effects were mild and included bone pain most likely attributable to pegfilgrastim. Neither granulocytopenia nor febrile neutropenia were seen and no treatments were delayed or postponed. Pegfilgrastim given on the same day as chemotherapy was effective in maintaining adequate granulocyte counts to allow treatment 14 days later and to avoid infection from granulocytopenia. Toxicity from pegfilgrastim was mild and tolerable. [Table: see text]

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