Primary Granulocyte Colony-stimulating Factor Prophylaxis Research Articles

The clinical impact of primary granulocyte-colony stimulating factor prophylaxis in children with acute lymphoblastic leukemia who underwent induction chemotherapy

BackgroundData describing the risk factors for the occurrence of severe infections in acute lymphoblastic leukemia (ALL) patients following induction chemotherapy and the role of prophylactic granulocyte-colony stimulating factor (G-CSF) in the era of antimicrobials prophylaxis are limited. MethodsThis study enrolled 188 children aged ≤18 years with newly diagnosed ALL who received Taiwan Pediatric Oncology Group ALL-2002 and 2013 treatments between January 1, 2010 and June 30, 2021. Prophylactic G-CSF was administered when a patient continues neutropenia after achieving the first bone marrow remission since June 1, 2015. Clinical factors were assessed for their association with severe infections. ResultsFrom January 2010 to May 2015, 80 children experienced a total of 11 (13.5%) episodes of severe infections; while 10 (9.2%) episodes were reported to occur in 108 patients who received prophylactic G-CSF. Reduction of severe infections occurrence did not achieve statistical significance during prophylactic G-CSF administration in ALL patients. Compared with ALL-high risk (HR) and very high risk patients with no G-CSF prophylaxis, the use of G-CSF prophylaxis significantly reduced episodes of febrile neutropenia. Occurrence of grade III-IV intestinal ileus, grade II-III oral mucositis, prolonged neutropenia, central venous catheter (CVC) placement, or the requirement insulin therapy for hyperglycemia were associated with higher risk of bloodstream infections. ConclusionsALL-HR patients with G-CSF prophylaxis were associated with reduction of febrile neutropenia episodes. Occurrence of severe ileus, oral mucositis, hyperglycemia, CVC placement, or prolonged neutropenia were associated with severe infections in ALL patients receiving induction chemotherapy.

Effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for invasive breast cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the Use of G-CSF 2022.

Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy. A systematic literature review was conducted according to the "Minds Handbook for Clinical Practice Guideline Development" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data. Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01-0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported. Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.

Primary prophylaxis with G-CSF for patients with non-round cell soft tissue sarcomas: a systematic review for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.

Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?" for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology. A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain. Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review. The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: "The benefit of primary G-CSF prophylaxis is not clear in NRC-STS" and "The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs." G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven.

DEFENDOR: Real-world evidence of primary prolonged G-CSF prophylaxis by empegfilgrastim for relative dose intensity compliance in patients with solid tumors—The final analysis.

e24109 Background: Myelosuppression management under chemotherapy (CT) is crucial for maintaining the relative dose intensity (RDI) of therapy and ensuring effective treatment of patients with solid tumors (ST). RDI > 85% is associated with better overall survival for the most ST. Granulocyte colony stimulating factors (G-CSF) have been the standard of care for the prevention of chemotherapy-induced neutropenia (CIN). Here we present the final results of a multicenter prospective observational post-marketing study of safety and efficacy of pegylated G-CSF Extimia (INN: empegfilgrastim, JSC BIOCAD) in pts with ST who receive cytotoxic therapy. Methods: The primary endpoint was the RDI of CT courses (4-8 cycles per course are allowed) with empegfilgrastim support. RDI was calculated for each single agent in the chemotherapy-based (CTb) regimen and for the CTb regimen in total. Extimia (7,5 mg) was administered subcutaneously once per chemotherapy cycle. Results: The study included 3218 pts with various tumor types across 41 centers in Russia. 3217 (99.97%) pts received at least one dose of the study drug. 2663 (82.8%) pts were included in the RDI assessment population per protocol. The average age of pts was 56.9 (18–84) y.o. Individuals aged ≥65 y.o accounted for almost one third of all pts. RDI ≥ 85% was achieved in 2415 (90.7%) pts (Table 1). 1447 (54.3%) pts have at least one FN risk factor whereas age ≥ 65 years is the most common (763/2663 (28.6%) pts). 91.5% RDI was registered in pts < 65 y.o and 88.7% RDI - in pts ≥ 65 y.o. Neutropenia was reported in 19 (0.7%) cases as a reason of RDI decrease. Grade 3-4 AEs were recorded in 74 (1.8%) cases in 59 pts whereas neutropenia (n = 22), anemia (n = 8) and diarrhea (n = 6) were the most common (CTCAE (v. 5.0)). Conclusions: Primary prolonged G-CSF prophylaxis by empegfilgrastim allows effectively maintaining RDI across various tumor types (TT) and treatment groups in pts with ST in routine clinical practice. Clinical trial information: NCT0481144 . [Table: see text]

Effectiveness and safety of primary prophylaxis of G-CSF during chemotherapy for prostate cancer, Japanese clinical guideline for appropriate use of G-CSF: clinical practice guidelines for the use of G-CSF 2022.

Docetaxel (DTX) is commonly used as a primary chemotherapy, and cabazitaxel (CBZ) has shown efficacy in patients who are DTX resistant. Primary prophylactic granulocyte colony stimulating factor (G-CSF) therapy is currently used with CBZ treatment in routine clinical care in Japan. In this study, we performed a systematic review following the Minds guidelines to investigate the effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for prostate cancer and to construct G-CSF guidelines for primary prophylaxis use during chemotherapy. A comprehensive literature search of various electronic databases (PubMed, Cochrane Library, and Ichushi) was performed on January 10, 2020, to identify studies published between January 1990 and December 31, 2019 that investigate the impact of primary prophylaxis with G-CSF during CBZ administration on clinical outcomes. Ultimately, nine articles were included in the qualitative systematic review. Primary G-CSF prophylaxis during CBZ administration for metastatic castration-resistant prostate cancer was difficult to assess in terms of correlation with overall survival, mortality from infection, and patients' quality of life. These difficulties were owing to the lack of randomized controlled trials comparing patients with and without primary prophylaxis of G-CSF during CBZ administration. However, some retrospective studies have suggested that it may reduce the incidence of febrile neutropenia. G-CSF may be beneficial as primary prophylaxis during CBZ administration for metastatic castration resistant prostate cancer, and we made a "weak recommendation to perform" with an annotation of the relevant regimen.

Effectiveness and safety of primary prophylaxis with G-CSF for lung cancer: a systematic review and meta-analysis to develop clinical practice guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of febrile neutropenia (FN) surpasses 20%. While primary prophylaxis with G-CSF has been proven effective in preventing FN in patients with cancer, there is limited evidence regarding its efficacy in specifically, lung cancer. Our systematic review focused on the efficacy of G-CSF primary prophylaxis in lung cancer. We extracted studies on non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using the PubMed, Ichushi Web, and Cochrane Library databases. Two reviewers assessed the extracted studies for each type of lung cancer and conducted quantitative and meta-analyses of preplanned outcomes, including overall survival, FN incidence, infection-related mortality, quality of life, and musculoskeletal pain. A limited number of studies were extracted: two on NSCLC and six on SCLC. A meta-analysis was not conducted owing to insufficient data on NSCLC. Two case-control studies explored the efficacy of primary prophylaxis with G-CSF in patients with NSCLC (on docetaxel and ramucirumab therapy) and indicated a lower FN frequency with G-CSF. For SCLC, meta-analysis of five studies showed no significant reduction in FN incidence, with an odds ratio of 0.38 (95% confidence interval 0.03-5.56, P = 0.48). Outcomes other than FN incidence could not be evaluated due to low data availability. Limited data are available on G-CSF prophylaxis in lung cancer. Primary prophylaxis with G-CSF may be weakly recommended in Japanese patients with NSCLC undergoing docetaxel and ramucirumab combination therapy.

A retrospective cohort study to monitor real-world safety in patients with locally advanced or metastatic urothelial carcinoma (LA/mUC) treated with sacituzumab govitecan (SG) in the United States.

608 Background: Patients with LA/mUC experience poor outcomes, with few treatment options historically available. In April 2021, SG (a TROP-2-directed antibody drug conjugate) received accelerated approval for patients with LA/mUC who progressed after platinum-based chemotherapy and immune checkpoint inhibitor therapy, based on the pivotal TROPHY U-01 trial (NCT03547973). We sought to evaluate SG safety in patients with LA/mUC treated in routine clinical practice in this study. Methods: A retrospective cohort of patients aged ≥ 18 years with LA/mUC treated with SG in the United States was evaluated using data from the nationwide Flatiron Health electronic health record–derived de-identified database (from Jan 2011 to Oct 2022). Outcomes included patient characteristics, treatment patterns, adverse events (AEs) of interest incidence, and granulocyte-colony stimulating factor (G-CSF) use. Descriptive statistics were used for data analysis. Results: This study included 86SG-treated patients (male, 70%; median age, 71 [range: 25-85] years; 27% with ECOG ≥ 2; 84% treated in community settings). Most patients (71%) received enfortumab vedotin (EV) in the direct prior line. The majority of patients received SG as monotherapy (94%), with most patients overall (99%) receiving SG as second-line (2L) or later. The most common AEs of interest (any grade, overall) were diarrhea (35%), neutropenia (40%) and nausea/vomiting (21%) (Table). Of the 86 patients, 14 (16%) patients were hospitalized, 8 (9%) discontinued SG treatment likely due to AEs/toxicity, and 3 (3%) died during or within 7 days after the line of treatment. During SG treatment, 52% of patients used G-CSF (primary prophylaxis 24%; secondary prophylaxis 19%; therapeutic use 28%). Only 1 (4.5%) patient who had primary G-CSF prophylaxis developed grade ≥ 3 neutropenia. Conclusions: This study is the largest analysis of SG use in a real-world population with LA/mUC to date; it provides insights into the safety of SG in this setting. Compared with prior data, this real-world population was older, with poorer functionality, and the majority received EV in the direct prior line. Observed AEs were consistent with the known safety profile of SG and indicate that this sequencing is feasible. [Table: see text]

Incidence and risk factors for febrile neutropenia of patients with diffuse large B-cell lymphoma receiving R-CHOP-21 in China

ObjectiveFebrile neutropenia (FN) is a serious complication of patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP-21. The prophylactic use of granulocyte colony–stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSFs for patients receiving chemotherapy with FN risk of 20% or 10 to 20% with defined risk factors. However, there are few studies on the incidence and risk factors of FN in patients with DLBCL receiving R-CHOP-21, especially in patients without primary G-CSF prophylaxis.MethodsWe conducted a retrospective analysis for the clinical data of 103 patients with DLBCL who underwent first R-CHOP-21 without primary G-CSF prophylaxis. The objective of the assessment was the incidence and risk factors of FN after the first chemotherapy cycle.ResultsAfter the first chemotherapy cycle, the incidence of FN was 20.4%. Multivariate analysis showed that age ≥ 65 years, bone marrow involvement, albumin < 35 g/L, and average relative dose intensity ≥ 80% were independent risk factors for FN. According to risk factors, we created a risk score system. The incidence of FN in the low-, intermediate- and high-risk groups was 5.6%, 17.2%, and 61.9%, respectively.ConclusionOur data indicated that R-CHOP-21 itself is associated with a high-risk regiment for FN. We recommend that intermediate/high-risk patients should actively consider primary G-CSF prophylaxis to reduce the incidence of FN after chemotherapy.

Febrile neutropenia incidence and the variable toxicity profile between brand and generic docetaxel in the adjuvant treatment of breast cancer with docetaxel and cyclophosphamide regimen.

To assess the incidence of febrile neutropenia without primary granulocyte colony-stimulating factor prophylaxis in patients undergoing chemotherapy with adjuvant docetaxel and cyclophosphamide, and to evaluate the toxicity profile of brand-name docetaxel (Taxotere ® ) and the generic formulation. This retrospective study was conducted using data obtained from electronic medical records of patients treated at a Brazilian cancer center. Patients with breast cancer who underwent adjuvant treatment between January 2016 and June 2019 were selected. Data were analyzed using chi-square and Fisher correlation of variables, and multivariate analyses were adjusted for propensity score. A total of 231 patients with a mean age of 55.9 years at the time of treatment were included in the study. The majority (93.9%) had luminal histology, 84.8% were at clinical stage I, and 98.2% had a good performance status. The overall incidence of febrile neutropenia in the study population was 13.4% (31 cases). The use of brand-name docetaxel (Taxotere ® ) was the only factor associated with febrile neutropenia occurrence (OR= 3.55, 95%CI= 1.58-7.94, p=0.002). In patients with breast cancer who require treatment with adjuvant docetaxel and cyclophosphamide regimen, the toxicity profile differs between brand-name and generic docetaxel. Regardless of the formulation used, the incidence of febrile neutropenia was less than 20%, which may allow for the omission of primary prophylactic granulocyte colony-stimulating factor use in this setting.

Subcutaneous Epcoritamab Plus Lenalidomide in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma from EPCORE NHL-5

Background: The prognosis for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor, even if treated with salvage chemotherapy and autologous stem cell transplantation. CAR T cell therapy provides long-term remission in only 40% of patients. Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody developed using the DuoBody ® platform, received accelerated FDA approval for adults with R/R DLBCL not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥2 lines of systemic therapy. Single-agent epcoritamab has demonstrated deep and durable responses (overall response rate, 63%; complete responses, 40%) and a manageable safety profile in patients with R/R large B-cell lymphoma in the EPCORE NHL-1 trial (Karimi et al, ASCO 2023, abstract 7525). Combining epcoritamab with antineoplastic agents that have different mechanisms of action may offer enhanced clinical benefit to patients. Therefore, EPCORE NHL-5 (NCT05283720) evaluated the safety, tolerability, and preliminary efficacy of epcoritamab, as well as defining its recommended dose when coadministered with other antineoplastic agents in patients with non-Hodgkin lymphoma. Here, we present results from arm 1 that evaluated epcoritamab combined with lenalidomide in patients with R/R DLBCL. Methods: EPCORE NHL-5 is a phase 1b/2, nonrandomized, open-label, multicenter study. In arm 1, adults with CD20 + R/R DLBCL (ECOG 0-2) received subcutaneous epcoritamab (weekly during cycle 1-3, every 4 weeks during cycle 4-12) and oral lenalidomide (once daily on days 1-21) for 12 cycles of 28 days. Patients had received at least 1 prior combined systemic therapy that contained an anti-CD20 monoclonal antibody. The primary endpoint was the identification of dose-limiting toxicities (DLTs). Key secondary endpoints included investigator-assessed best overall response by Lugano 2014 criteria and time to response. Safety endpoints included severity and incidence of adverse events (AEs) including AEs of special interest to epcoritamab (cytokine release syndrome [CRS], immune cell-associated neurotoxicity syndrome [ICANS], and clinical tumor lysis syndrome). Results: As of May 22, 2023, 26 patients (median age, 71 years; DLBCL, n=24 [92%]; follicular lymphoma grade [G] 3b, n=2 [8%]) had received epcoritamab plus lenalidomide. Median duration of epcoritamab exposure was 3.8 months (range, 0-7.5) and median duration of lenalidomide exposure was 4.0 months (range, 0.1-8.2); 15 patients (58%) remain on epcoritamab and lenalidomide. Median number of prior lines of therapy was 1 (range, 1-4), with 15 (58%) receiving 1 prior line of anticancer therapy. Six patients (23%) had received prior CAR T and 2 patients had undergone hematopoietic stem cell transplantation. One DLT (neutropenia) was observed. The most common G3-4 treatment-emergent AEs (TEAEs) were neutropenia (n=15; 58%), anemia (n=4; 15%), thrombocytopenia (n=4; 15%), and febrile neutropenia (n=3; 12%). Primary granulocyte colony-stimulating factor prophylaxis was not mandatory. TEAEs led to epcoritamab discontinuation in 1 patient (3.8%; thrombocytopenia). No patients experienced a TEAE leading to death that was considered related to epcoritamab. CRS was predominantly low grade (73% [19/26] any grade; 65% G1-2; 8% G3) and occurred mostly after the first full dose (C1D15). Preliminary biomarker analysis showed pharmacodynamic profiles consistent with the mechanism of action of epcoritamab. These include predictable cytokine peaks immediately after the first full dose (IFN-gamma, IL-2, and IL-6) with a rapid and sustained depletion of peripheral B cells. One patient experienced ICANS (G3), which resolved after 2 days. Among response-evaluable patients (n=24), the overall response rate was 75% (95% CI, 53.3, 90.2). Complete metabolic responses were seen in 14 patients (58%) and partial responses in 4 patients (17%), of which 3 were ongoing at time of data cutoff ( Table). Median time to first response was 1.8 months (range, 1.0-2.8). Follow-up is ongoing. Conclusions: Epcoritamab combined with lenalidomide showed promising antitumor activity with a tolerable safety profile in patients with R/R DLBCL.

Optimizing GCSF prophylaxis: Artificial intelligence (AI) models to predict chemotherapy-induced FN in patients with cancer.

547 Background: NCCN guidelines recommend primary prophylaxis with granulocyte-colony stimulating factors (GCSF) for select risk classifications; however, the recommendations for a patient at &lt;20% risk of FN are not as explicit. This study builds on previously developed FN risk models and aims to use AI modeling techniques to predict individual risk of neutropenic complications in patients receiving cancer treatment. Methods: An AI-based FN risk modeling study was conducted using retrospective administrative claims of adult commercial and Medicare Advantage patients treated for non-myeloid malignancies from Jan 01 2009 to March 31 2020. Exclusions were myeloid malignancy, pregnancy, clinical trial participation, HIV positive status, hematopoietic cell transplantation, baseline GCSF, surgery or radiation in the first six days of the first chemotherapy cycle. Model features included baseline patient clinical and demographic characteristics, baseline HCRU, chemotherapy treatment patterns, FN risk factors, and use of primary GCSF prophylaxis. The models were developed with an 80/20 train/test split and compared using standard measures of goodness of fit. Various traditional and AI techniques, such as logistic and lasso regressions, TensorFlow Keras, and XGBoost, were trained to predict FN events in this sample. Based on performance, XGBoost was selected for analysis (ROC of 0.86). Results: The sample comprised of (mean age 68 years, 50% female). Among 17,233 patients (20% test set), 2,773 patients (all risk categories) received primary GCSF prophylaxis; 14,460 patients did not receive primary GCSF prophylaxis. The top 20% risk score threshold was deemed optimal to identify high-risk patients. Model outcomes were bifurcated and analyzed based on NCCN guided risk levels; for the high risk chemo regimen, intermediate risk regimen, and remaining patients without primary GCSF prophylaxis, model sensitivity was 74%, 88%, and 56% respectively. Model specifications for the overall top 20% of the test cohort without primary GCSF prophylaxis are described in the table as overall, high risk, intermediate risk, and other risk subsets. Conclusions: While the XGBoost model provided the best fit, the logistic regression model is a strong candidate to identify characteristics associated with higher odds of an FN event. Through identification of these characteristics, the rate of FN in this population can be better addressed and optimize utilization of GCSFs for primary prophylaxis.[Table: see text]

Efficacy of bi-weekly docetaxel in hormone-sensitive metastatic prostate cancer (mHSPC).

e17070 Background: In pts with mHSPC, docetaxel in a three-week schedule is associated with better overall survival (OS) vs androgen suppression alone, principally in pts with high tumor volume(HV). In pts with mCRPC stage, biweekly docetaxel demonstrated greater efficacy and a better toxicity profile. There are few published data about the use of bi-weekly docetaxel in pts with mHSPC. Methods: Pts with mHSPC and treated with bi-weekly docetaxel from January 2014 to December 2020 at The Comprehensive Cancer Center Clinica de Occidente in Cali-Colombia, were retrospectively identified. We collected relevant variables from electronic medical records. Our primary objective was to determine the efficacy in OS and the incidence of febrile neutropenia (FN). We performed Kaplan Meier, and cox regression analysis with relevant variables. Results: 69 pts were included, with a mean follow-up time of 45 months. Median age was 72y, 82% had ECOG PS 0/1, 74% grade group 4-5, 23% visceral metastases, and 93% de novo metastatic disease. The median OS was 51 months, and 39% at 5 years. In HV and de novo metastatic pts, the median OS was 49 months. The median time to development of mCRPC was 34 months. 35% of the patients had a PSA &lt; 0.2ng/mL at month 6. In the univariate analysis, pts with HV (HR 10.49 95% CI 1.43-76.50, P = 0.0005), PSA &gt; 0.2ng/mL (HR 4.43 95% CI 2.09-9.41, P = 0.0000), imagen objective response rate (ORR) (HR 1.47 95% CI 1.09-1.95, P = 0.0156) and PS ECOG &gt; 0, (HR 3.3 CI95% 1.31-8.45, P = 0.003) had worse OS. Neither histologic grade 5 (HR 1.07, P = 0.8), visceral metastases (HR 1.2, P = 0.57), or de novo metastatic disease (HR 0.84, P = 0.74) were significantly associated. In the multivariate analysis, only PSA of &gt; 0.2ng/mL at 6 months remained significantly [Table 1]. FN was detected in 3.2% of patients. Conclusions: We report the study with the largest number of patients and follow-up time (median 42.5 months) in patients with mCSPC who used biweekly docetaxel in addition to standard androgen suppression. The outcomes are similar, indirectly compared, to those reported in the CHAARTED study in OS, specifically in the de novo high-volume metastatic subgroup (CHAARTED 48 months, current study 49 months), better time to CRPC (20 months CHAARTED, 34 months current study), and with a lower incidence of FN (6% CHAARTED, 2% current study). None of the pts used primary granulocyte colony-stimulating factor prophylaxis. The use of biweekly docetaxel in this scenario offers high efficacy with less toxicity. Randomized studies are strongly recommended to confirm these results. [Table: see text]

Effects of primary granulocyte-colony stimulating factor prophylaxis on neutropenic toxicity and chemotherapy dose delivery in Chinese patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy: a retrospective cohort study.

This study was performed to examine the effects of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on neutropenic toxicity, chemotherapy delivery, and hospitalisation among Chinese patients with breast cancer in Hong Kong. This retrospective study included patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy from November 2007 to October 2013 at Princess Margaret Hospital. Data were collected regarding the usage of G-CSF prophylaxis; incidences of grade 3 or 4 neutropenia, febrile neutropenia, non-neutropenic fever, and infection; hospital admissions, and chemotherapy dose delivery. Patients who began to receive G-CSF prophylaxis during the first cycle of chemotherapy and continued such prophylaxis in subsequent cycles were regarded as the primary G-CSF prophylaxis group. In total, 231 female Chinese patients with breast cancer were included in the analysis. Overall, 193 (83.5%) patients received primary G-CSF prophylaxis. The demographics and tumour characteristics were comparable between patients with and without primary G-CSF prophylaxis. Primary G-CSF prophylaxis significantly reduced febrile neutropenia incidence from 31.6% to 14.5% (relative risk=0.45, 95% confidence interval=0.25-0.81). Primary G-CSF prophylaxis also significantly reduced the incidence of grade 3 or 4 neutropenia from 57.9% to 24.7% (relative risk=0.43, 95% confidence interval=0.30-0.62) and the incidence of febrile neutropenia-related hospital admission from 31.6% to 12.4% (P=0.025). Finally, it enabled more patients to receive adequate chemotherapy dose delivery. Primary G-CSF prophylaxis effectively reduced the incidences of grade 3 or 4 neutropenia and febrile neutropenia, while enabling adequate chemotherapy dose delivery and reducing hospital admissions among Chinese patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy.

Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial

Lurbinectedin is a synthetic marine-derived anticancer agent that acts as a selective inhibitor of oncogenic transcription. Lurbinectedin monotherapy (3·2 mg/m2 every 3 weeks) received accelerated approval from the US Food and Drug Administration on the basis of efficacy in patients with small-cell lung cancer (SCLC) who relapsed after first-line platinum-based chemotherapy. The ATLANTIS trial assessed the efficacy and safety of combination lurbinectedin and the anthracycline doxorubicin as second-line treatment for SCLC. In this phase 3, open-label, randomised study, adult patients aged 18 years or older with SCLC who relapsed after platinum-based chemotherapy were recruited from 135 hospitals across North America, South America, Europe, and the Middle East. Patients were randomly assigned (1:1) centrally by dynamic allocation to intravenous lurbinectedin 2·0 mg/m2 plus doxorubicin 40·0 mg/m2 administered on day 1 of 21-day cycles or physician's choice of control therapy (intravenous topotecan 1·5 mg/m2 on days 1-5 of 21-day cycles; or intravenous cyclophosphamide 1000 mg/m2, doxorubicin 45·0 mg/m2, and vincristine 2·0 mg on day 1 of 21-day cycles [CAV]) administered until disease progression or unacceptable toxicity. Primary granulocyte-colony stimulating factor prophylaxis was mandatory in both treatment groups. Neither patients nor clinicians were masked to treatment allocation, but the independent review committee, which assessed outcomes, was masked to patients' treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02566993, and with EudraCT, 2015-001641-89, and is complete. Between Aug 30, 2016, and Aug 20, 2018, 613 patients were randomly assigned to lurbinectedin plus doxorubicin (n=307) or control (topotecan, n=127; CAV, n=179) and comprised the intention-to-treat population; safety endpoints were assessed in patients who had received any partial or complete study treatment infusions (lurbinectedin plus doxorubicin, n=303; control, n=289). After a median follow-up of 24·1 months (95% CI 21·7-26·3), 303 patients in the lurbinectedin plus doxorubicin group and 289 patients in the control group had discontinued study treatment; progressive disease was the most common reason for discontinuation (213 [70%] patients in the lurbinectedin plus doxorubicin group vs 152 [53%] in the control group). Median overall survival was 8·6 months (95% CI 7·1-9·4) in the lurbinectedin plus doxorubicin group versus 7·6 months (6·6-8·2) in the control group (stratified log-rank p=0·90; hazard ratio 0·97 [95% CI 0·82-1·15], p=0·70). 12 patients died because of treatment-related adverse events: two (<1%) of 303 in the lurbinectedin plus doxorubicin group and ten (3%) of 289 in the control group. 296 (98%) of 303 patients in the lurbinectedin plus doxorubicin group had treatment-emergent adverse events compared with 284 (98%) of 289 patients in the control group; treatment-related adverse events occurred in 268 (88%) patients in the lurbinectedin plus doxorubicin group and 266 (92%) patients in the control group. Grade 3 or worse haematological adverse events were less frequent in the lurbinectedin plus doxorubicin group than the control group (anaemia, 57 [19%] of 302 patients in the lurbinectedin plus doxorubicin group vs 110 [38%] of 288 in the control group; neutropenia, 112 [37%] vs 200 [69%]; thrombocytopenia, 42 [14%] vs 90 [31%]). The frequency of treatment-related adverse events leading to treatment discontinuation was lower in the lurbinectedin plus doxorubicin group than in the control group (26 [9%] of 303 patients in the lurbinectedin plus doxorubicin group vs 47 [16%] of 289 in the control group). Combination therapy with lurbinectedin plus doxorubicin did not improve overall survival versus control in patients with relapsed SCLC. However, lurbinectedin plus doxorubicin showed a favourable haematological safety profile compared with control. PharmaMar.

Effects of primary granulocyte-colony stimulating factor prophylaxis on the incidence of febrile neutropenia in patients with germ cell tumors.

Testicular germ cell tumors (GCTs) are the most common solid malignancy in males aged 15–35 years. Febrile neutropenia (FN) is a serious complication of chemotherapy that frequently occurs in patients with GCTs. The present retrospective study aimed to evaluate the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in patients with GCTs. The present study included a review of the medical records of patients diagnosed with GCTs treated with first-line/adjuvant chemotherapy between January 2000 and December 2017 at the National Cancer Institute (Bratislava, Slovakia). In January 2006, a decision was made to administer G-CSF prophylaxis (filgrastim or pegfilgrastim) to patients after every cycle of chemotherapy. The present study included 385 patients, and out of these, 264 patients received primary G-CSF prophylaxis, while 121 patients did not. A total of 71 patients (18.4%) suffered from FN events. In the subgroup that did not receive primary prophylaxis, 42 patients exhibited FN, while only 29 patients with primary prophylaxis suffered from FN (34.7 vs. 11.0%; P=0.00000003). According to the subgroup analysis, FN incidence was decreased in all groups that received primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy, without affecting overall survival. Primary G-CSF prophylaxis was associated with markedly reduced FN incidence in patients treated with first-line chemotherapy for metastatic disease. Therefore, the results of the present study suggested that primary G-CSF prophylaxis should be considered in patients with GCT receiving first-line chemotherapy.

Underutilisation of prophylactic G-CSF in breast cancer patients receiving adjuvant docetaxel/cyclophosphamide chemotherapy

Docetaxel/cyclophosphamide (TC) is a widely used adjuvant chemotherapy regimen, especially in patients with node-negative or low-risk node-positive breast cancer. Guidelines recommend the use of prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent febrile neutropenia. In this study, we aimed to explore the use of G-CSF as a primary prophylactic and determine the factors influencing its use. This retrospective study used nationwide claims data from the National Inpatient Sample compiled by the Health Insurance Review and Assessment Service in South Korea from 2018. The claims data included 10% of inpatients admitted at least once in 2018 and 1% of outpatients who were not admitted. Female patients with breast cancer who received an adjuvant TC regimen after surgery were selected. Primary prophylactic G-CSF was defined as G-CSF prescribed within two days of the first cycle of TC. The factors influencing its utilisation were investigated using the chi-square test and a multiple logistic regression model. A total of 229 patients were included in the analysis. The proportion of patients who received primary prophylactic G-CSF treatment after the first cycle of TC was 55.5%. The factors positively influencing G-CSF utilization were patients’ age ≥65 years, location (i.e. metropolitan areas), and the type of healthcare facility (i.e. non-tertiary hospitals). The use of prophylactic G-CSF in patients with breast cancer who received the adjuvant TC regimen was insufficient. The use of primary G-CSF prophylaxis should be emphasised to reduce the risk of febrile neutropenia among patients receiving a myelosuppressive TC regimen.

Febrile neutropenia prophylaxis, G-CSF physician preferences: discrete-choice experiment

ObjectivesFebrile neutropenia (FN) commonly occurs during cancer chemotherapy. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is known to reduce the severity and incidence of FN and infections in patients with cancer....

Risk factors for neutropenic fever in non-Hodgkin's lymphoma patients with primary granulocyte colony-stimulating factor prophylaxis.

Background/AimsFebrile neutropenia (FN) interferes with the proper chemotherapy dose density or intensity in non-Hodgkin’s lymphoma (NHL) patients. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab has an intermediate FN risk. Prophylactic granulocyte colony-stimulating factor (G-CSF) support is recommended for patients with other host-related risk factors.MethodsWe evaluated the risk factors for FN-related admission in NHL patients who have received primary G-CSF (lenograstim) prophylaxis.ResultsData from 148 patients were analyzed. The incidence of neutropenic fever was 96 events (12.2%), and the median period was 3.85 days (range, 0 to 5.9); the median duration of neutropenia was 4.21 days (range, 3.3 to 5.07). Eighty-three FN-related admissions were reported. Advanced age (> 60 years), female sex, a low albumin level, and prednisone use were associated with FN-related admission in multivariable analysis (p = 0.010, p < 0.001, and p = 0.010, respectively). A comparison between diffuse large B-cell lymphoma patients treated with R-CHOP and pegylated G-CSF and those treated with R-CHOP and lenograstim did not reveal significant differences in the FN-related admission rate between the two groups, although the lenograstim-treated group had a higher incidence of severe neutropenia.ConclusionsElderly patients, female patients, and patients with low albumin levels need to be actively followed-up for FN even when primary prophylaxis with G-CSF has been used.

Prevention of docetaxel-associated febrile neutropenia with primary granulocyte colony-stimulating factor in Chinese metastatic hormone-sensitive and castration-resistant prostate cancer patients.

Asian prostate cancer (PC) patients are particularly susceptible to docetaxel-related febrile neutropenia (FN). We evaluated primary granulocyte colony-stimulating factor (GCSF) for preventing FN in Chinese patients with metastatic hormone-sensitive PC (mHSPC) and castration-resistant PC (mCRPC). Data from two cohorts of 377 Chinese patients with mHSPC (100; 26.5%) and mCRPC (277; 73.5%) treated with docetaxel at six public oncology centres were analysed with multivariate regression. Primary GCSF prophylaxis was defined as administration within 5 days of starting docetaxel. The primary outcome was FN within 21 days of the first docetaxel cycle (1st FN). Primary GCSF was given to 71 (18.8%) patients. FN occurred in 61 patients (16.2%) including 37 (9.8%) during the first cycle. Among patients who developed 1st cycle FN (n=37) or not (n=340), 2 and 69 received primary GCSF (5.4vs. 20.3%, P=.03). Primary GCSF was associated with an overall reduced risk of 1st cycle FN (odds ratio [OR]=0.22; 95% confidence interval [CI]: 0.05-0.96, P=.04), and similar trends were observed in the mHSPC (OR=0.36, P=.35) and mCRPC (OR=0.16, P=.08) subgroups. Poor Eastern Cooperative Oncology Group performance status(>1) was associated with an increased risk of 1st FN (OR=3.90; 95% CI: 1.66-9.13, P=.002). To alleviate the risk of docetaxel-related FN, primary GCSF prophylaxis is suggested for Asian mCRPC and mHSPC patients, particularly those with poor performance status.

Abstract PS11-15: Plinabulin and pegfilgrastim (Plin+Peg) versus peg monotherapy (Peg) after TAC: A comparison of efficacy, safety, relative dose intensity (RDI) and bone pain

Abstract Introduction:Prevention of Chemotherapy Induced Neutropenia (CIN) through primary or secondary prophylaxis is indicated in breast cancer (BC) chemotherapy (chemo) which is administered with curative intent. Granulocyte colony stimulating factors (G-CSFs), including Peg are standard of care in this context. In typical every three-week chemo regimens with primary G-CSF prophylaxis, absolute neutrophil count (ANC) nadir occur approximately day (D) 7, which reduces but does not eliminate febrile neutropenia risk in the first week. However, plinabulin (Plin), a novel non-G-CSF agent, protects against the nadir and CIN in the 1st week after chemo (Blayney ASCO 2019). These findings provided the rationale to combine Plin with Peg after chemo with a high febrile neutropenia risk. Both Plin and Peg act on the neutrophil precursor. Both agents mobilize bone marrow-derived CD34+ progenitor stem cells (Blayney ASH 2018). Plin has also anti-cancer efficacy in an animal BC model (Bertelsen, Int J Rad Biol 2011). Here we summarize the efficacy and safety data with combining Peg with Plin in potentially curable BC patients treated with TAC. Methods: In the randomized phase 2 portion of Study 106 (NCT0329457), BC patients were treated with TAC (docetaxel 75, doxorubicin 50 and cyclophosphamide 500 mg/m2) and either 6 mg Peg alone (Peg6; n=22), or Peg 6mg+Plin 20 mg/m2 (Plin+Peg; n=16). Grade (Gr) 3/4 neutropenia frequency, duration of Gr 3 and 4 neutropenia (DSMN), and neutrophil nadir was calculated from absolute neutrophil counts obtained on days 0, 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 15. Bone pain was assessed by a validated questionnaire. Percentage of pts with RDI &amp;lt;85% and adverse event rate (Grades 1-5) was calculated. Results: Gr 3 or 4 neutropenia with Plin/Peg vs Peg was 50% vs 81.1% (p&amp;lt;0.04). Median DSMN with Plin/Peg vs Peg was 0.5 day vs 1 day. ANC nadir [mean (95% CI)] with Plin/Peg vs Peg was 1.15 (0.66;1.65) vs 0.80 (0.37;1.22). In the Plin+Peg vs Peg group, Gr 4 AE frequency was 37.3% vs 54.5%, Gr 3 AE frequency was 18.8% vs 27.3%, Gr 2 AE frequency was 25% vs 9.1% and Gr 1 AE frequency was 18.8% vs 4.5%. No Gr 5 AEs occurred in either group. Bone pain was significantly less (P&amp;lt;0.001) with Plin+Peg vs Peg. Conclusion: Addition of Plin to Peg has superior prevention of CIN, superior safety, superior RDI and superior protection against bone pain compared to standard dose Peg alone in this randomized phase 2 trial. A confirmatory global Phase 3 trial comparing Plin+Peg vs Peg alone is underway. RDI&amp;lt;85%Cycle 1Cycle 2Cycle 3Cycle 4Peg0 %13.6 %19.1 %19.1 %Plin+Peg0 %6.25 %6.25 %6.25 % Citation Format: Douglas W. Blayney, Greg Ginn, Lan Huang, Ramon W. Mohanlal. Plinabulin and pegfilgrastim (Plin+Peg) versus peg monotherapy (Peg) after TAC: A comparison of efficacy, safety, relative dose intensity (RDI) and bone pain [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-15.