Prophylactic Granulocyte Colony-stimulating Factor Research Articles

Abstract PO1-12-06: Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia?

Abstract Background: Febrile neutropenia (FN), a major hematologic adverse event in perioperative chemotherapy for breast cancer, is more prevalent among Asians than in Caucasian populations. Four main guidelines, i.e., ASCO, EORTC, NCCN, and ESMO, provide recommendations regarding the appropriate use of hematopoietic growth factors. These guidelines recommend primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) based on the estimated incidence of FN, primarily defined by the chemotherapy regimen. G-CSF administration is recommended when the incidence of FN is ≥20% or 10–20% with risk(s). However, the incidence of FN varies depending on the trial and design, and patient-specific risk factors for FN remain unclear. We previously performed a multicenter prospective cohort study in Japan, the CSPOR-BC FN study, evaluating the incidence of FN during perioperative chemotherapy for breast cancer. Herein, we conducted an additional analysis to explore thresholds of patient-specific risk factors for FN that could be evaluated before chemotherapy. We analyzed the risk factors for FN and verified the appropriateness of patient selection for prophylactic G-CSF administration. Methods: The previously reported CSPOR-BC FN study (PubMed ID=33631458) consecutively enrolled 1005 patients with stage I–III breast cancer between August 2015 and July 2017. In the current additional analysis, we intended to have 477 patients in the visiting group that evaluated true-FN, defined as ≥37.5℃ and grade 4 neutropenia. Multivariate analysis of risk factors for FN was performed, followed by the determination of cutoff values for age and pretreatment absolute neutrophil count (ANC) as risk factors. Results: Chemotherapy regimens administered were FEC (fluorouracil, epirubicin, and cyclophosphamide) in 170 patients (36%), E(A)C (epirubicin (doxorubicin) + cyclophosphamide) in 165 patients (35%), and TC (docetaxel + cyclophosphamide) in 142 patients (30%). The incidence of FN was 28.7% (N = 137). To evaluate the risk factors for FN, we predefined regimens, age, performance status (PS), stage, chemotherapy or radiotherapy history, infectious wounds, open wounds, ANC, and renal and liver dysfunction as potential risk factors. Multivariate analysis of risk factors for FN identified regimen (TC), age (≥65), low pretreatment ANC, treatment setting, and no primary pegfilgrastim prophylaxis as significant risk factors. Two patient-specific risk factors (age and pretreatment ANC) were analyzed. Logistic regression analysis revealed that age≥65 years was a significant risk factor (odds ratio=2.24, 95% confidence interval: 1.34–3.75). Applying a cutoff of 65 years (age) to predict FN, the sensitivity and specificity were 28.4 and 83.8%, respectively, which were inaccurate. Despite applying a cutoff of 67 years optimized from the receiver operating characteristic (ROC) curve, the sensitivity (22.4%), specificity (90.7%), and area under the curve (0.519) indicated low discrimination for predicting FN. The incidence of FN by age group was as follows: < 45 years, 30.8%; 45–55 years, 26.4%; 55–64 years, 20.9%; ≥65 years, 39.6%. Additionally, applying a cutoff of 2436/µL (pretreatment ANC) optimized from the ROC curve, the observed sensitivity (27.6%) and specificity (83.8%), and area under the curve (0.558) also indicated low discrimination for predicting FN. The incidence of FN by stratum of pretreatment ANC was as follows: < 2000, 33.3%; 2000–3000, 30.7%; 3000–4000, 29.9%; and >4000, 24.6. Accordingly, setting a cutoff value to predict FN incidence using age and/or pretreatment ANC was deemed inappropriate. Conclusion: Selecting patients for primary prophylactic G-CSF based on the existing FN risk can be challenging. Primary prophylactic G-CSF would be considered for every patient undergoing perioperative chemotherapy for breast cancer, especially Asians. ROC curve for FN and age. The AUC was 0.519. ROC curve for FN and neutrophil count. The AUC was 0.558. Citation Format: Kazutaka Narui, Takashi Ishikawa, Ikumi Takashima, Kosuke Kashiwabara, Yukari Uemura, Yuichiro Kikawa, Naruto Taira, Hirofumi Mukai. Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-06.

Abstract PO5-16-11: Novel antibody-drug-conjugates in clinical routine: adherence, efficacy and tolerability - real-world data from German breast centers

Abstract The third-generation antibody-drug conjugates, Trastuzumab-Deruxtecan (T-DXd) and Sacituzumab Govitecan (SG), have been approved for the treatment of metastatic breast carcinoma in various subtypes and therapeutic settings based on compelling Phase III study data. (DESTINY-Breast03 (T-DXd; HER2-positive), DESTINY-Breast04 (T-DXd; HER2-low), ASCENT (SG; triple-negative), and TROPiCS-02 (SG; HR+/HER2-negative). The aim of this retrospective study conducted at two major German Breast centers was to evaluate the tolerability, adherence, and efficacy of both substances in the real-world setting. All patients treated outside of clinical trials with T-DXd or SG at the Department of Gynecology and Obstetrics, Ulm University Hospital and the Department of Women’s Health, Tuebingen University Hospital between November 2020 and May 2023 were included in this retrospective analysis. Seventy-five patients were included [T-DXd: 46; SG: 29]. The mean duration of therapy was 5.4 months [T-DXd: 6.2; SG: 4.2]. The real-world cohort was more heavily pretreated than the corresponding study cohorts, with a mean of 4.2 systemic therapies in the metastatic setting prior to T-DXd therapy and 3.6 systemic therapies prior to SG therapy. The administered cumulative dose on average was 87.9% [T-DXd: 94%; SG: 79%] of the theoretical full dose or 95.3% [T-DXd: 98%; SG: 92%] when considering dose reductions that occurred. Hematotoxicities of CTC ≥ 3° occurred in 11% of patients treated with T-DXd and in 41% of patients treated with SG. Neutropenia was the predominant severe hematotoxicity (CTC≥III°) observed during SG therapy, occurring in 38% of patients. The occurrence of neutropenia during SG therapy was reduced with primary prophylactic administration of Granulocyte-Colony Stimulating Factor (GCSF), with a rate of 29% (21/29) of patients experiencing neutropenia ≥CTC-III°, compared to 63% (8/29) without primary prophylactic GCSF. Therapy-associated pneumonitis under T-DXd occurred in 5 out of the 46 included patients and was successfully treated with corticosteroids in all cases (CTC II° in 4 cases, CTC III° in 1 case). The median progression-free survival (PFS) from initial administration was 7.7 months under T-DXd [HER2-positive: 9.0; HER2-low: 6.1], and 4.8 months under SG [TNBC 4.8; HR+/HER2-negative: 2.8]. The median overall survival from initial administration was 27.1 months under T-DXd [HER2-positive: 27.1; HER2-low: not reached], and 11.9 months under SG therapy [TNBC: 11.0, HR+/HER2-negative: not reached]. This analysis provides evidence of the efficacy and tolerability of T-DXd and SG in a heterogeneous and heavily pretreated cohort in a real-world setting. However, a conclusive assessment of progression-free survival (PFS) and overall survival (OS) is not feasible yet, as a substantial number of patients are still under treatment. Updated PFS and OS data, with a specific focus on the therapy indication, will be presented at the meeting. Citation Format: Henning Schäffler, Dominik Dannehl, Kristina Veselinovic, Franziska Mergel, Kerstin Pfister, Brigitte Rack, Visnja Fink, Elena Leinert, Lea Volmer, Tobias Engler, Sara Brucker, Wolfgang Janni, Andreas Hartkopf. Novel antibody-drug-conjugates in clinical routine: adherence, efficacy and tolerability - real-world data from German breast centers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-11.

Abstract PO2-18-02: Utilization of Granulocyte Colony-Stimulating Factor (GCSF) in the Management of Patients (pts) on Sacituzumab Govitecan-hziy (SG) and Impact on Duration of Therapy (DOT)

Abstract Background: An examination was conducted to understand the prevalence of neutropenia in pts managed with SG in the real-world setting, as the ASCENT trial demonstrated a 63% rate of neutropenia in those pts treated with SG1. In addition, an assessment was performed to see whether pts who developed neutropenia on SG received a GCSF and how GCSF use impacted pt DOT on SG. Methods: This assessment utilized the Integra Connect PrecisionQ real-world de-identified database of over 2 million cancer pts across 500 sites of care to evaluate the prevalence of neutropenia (< 1500 neutrophils) among those who were treated with SG, GCSF utilization among those with neutropenia, and the difference in DOT between neutropenic pts who received a GCSF and those who did not. In analyzing the DOT, pts were required to have had a follow-up of 12 months or greater. The SG pts data utilized reflects treatments through May 31, 2023. Comparisons of median DOT were conducted using a Wilcoxon Rank Sum test. Descriptive analyses were used to summarize pt demographic statistics. Results: 447 pts treated with SG were identified with an average age at treatment start of 58.5 (median of 60); 15% identified as Black or African American and 69% identified as White or Caucasian. Of the 447 pts treated with SG, 98% (N = 438) developed neutropenia while on therapy. Among those 438 pts who developed neutropenia, 61% received a GCSF and 39% did not. Of the 330 pts with at least 12 months of follow-up, the median DOT was 119.5 days. Among the 204 pts who received a GCSF, the median DOT was 147 days, compared to a median DOT of 97 days for the 126 pts who did not receive a GCSF (p < 0.001). Conclusion: The DOT for pts treated with SG who received a GCSF was longer than those who did not receive a GCSF while treated with SG. This assessment revealed that approximately 40% of SG treated pts who developed neutropenia did not receive a GCSF. Thus, increasing utilization of GCSFs presents an opportunity to improve management of pts who develop neutropenia while on SG to extend the time on therapy and potentially delay disease progression. These findings warrant further research on the use of prophylactic GCSFs for managing pts who receive SG and suggest further clinical guidance may be needed to provide best practices for managing pts on SG. [1] Rugo, H.S., Tolaney, S.M., Loirat, D. et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. npj Breast Cancer 8, 98 (2022). https://doi.org/10.1038/s41523-022-00467-1 Citation Format: Vikram Gorantla, Erin Alwon, Mike Gart, John Li, Simon Blanc, Dawn Brenneman, Emma Genser, Prateesh Varughese, Justin Scott, Harvey Katzen. Utilization of Granulocyte Colony-Stimulating Factor (GCSF) in the Management of Patients (pts) on Sacituzumab Govitecan-hziy (SG) and Impact on Duration of Therapy (DOT) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-18-02.

Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony-stimulating factor following chemotherapy: Triangulation of evidence using population-based cohort and Mendelian randomization analyses.

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

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.

Safety and efficacy of nanosomal docetaxel lipid suspension (NDLS) in patients with advanced gastric adenocarcinoma.

348 Background: Nanosomal docetaxel lipid suspension (NDLS) was developed to overcome toxicity issues associated with conventional docetaxel. Docetaxel, cisplatin, 5-fluorouracil (5-FU; DCF) or modified DCF (mDCF) is one of the recommended first-line regimens for patients with metastatic gastric adenocarcinoma (GAC). However, majority of the patients experienced grade 3/4 toxicities with DCF regimen using conventional docetaxel. The present study evaluated the safety and efficacy of NDLS-based mDCF/DCF regimens in patients with metastatic GAC. Methods: In this multicentric, open-label, clinical trial, patients with previously untreated metastatic GAC were enrolled. Patients received either mDCF [NDLS 40 mg/m2 on day 1 (D1), C 40 mg/m2 on D2 or D3, 5-FU 400 mg/m2 bolus on D1, leucovorin 400 mg/m2 on D1, 5-FU 1000 mg/m2/day continuous infusion D1 & 2; q2w] for 9 cycles, or DCF [NDLS 75 mg/m2 on D1, C 75 mg/m2 on D1, 5-FU 750 mg/m2/day for 5 days given as continuous infusion; q3w] for 6 cycles. Prophylactic GCSF (Granulocyte Colony Stimulating Factor)/Peg-GCSF support was allowed in all patients. The primary endpoint was overall response rate (ORR) at week 18. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety outcomes. Patients were followed up to 1 year. Results: Fifty-two patients were enrolled, with mean (±SD) age of 52 (±9.6) years & male:female ratio of 32:20. Thirty-eight patients qualified for modified intent-to-treat (mITT) analysis for efficacy evaluation (mDCF: 33; DCF:5). At week 18, ORR was 57.9% & DCR was 81.6% in mITT population. In the per-protocol population (n=26), ORR was 61.5% at 18 weeks (mDCF:63.6%; DCF:50%). Safety set included all 52 patients. Any grade adverse events (AEs) were reported in 90.4% (n=47) of the patients; with 40.4% experiencing grade 3/4 AEs. All-grade AEs reported in ≥10% of the patients included anemia, neutropenia, abdominal pain, diarrhea, nausea, vomiting, fatigue, mucositis, decreased appetite, peripheral neuropathy; with majority of AEs being grade 1/2. Most common grade 3/4 AE was neutropenia; observed in 17.3% (n=9) patients (mDCF: 14%; DCF: 33.3%). Conclusions: NDLS-based regimens demonstrated efficacy & improved safety profile in the treatment of metastatic GAC. Clinical trial information: CTRI/2018/01/011450 . [Table: see text]

Whole-Brain Radiotherapy Alone vs Preceded by Bevacizumab, Etoposide, and Cisplatin for Untreated Brain Metastases From Breast Cancer

The incidence of brain metastasis is increasing in patients with metastatic breast cancer. Treatments to extend the control of brain metastasis are urgently required. To investigate whether the addition of an induction treatment of bevacizumab, etoposide, and cisplatin (BEEP) improves brain-specific progression-free survival (PFS) after whole-brain radiotherapy (WBRT). This open-label, randomized, multicenter clinical trial assessed patients with brain metastases from breast cancer (BMBC) in Taiwan from September 9, 2014, to December 24, 2018, with survival follow-up until December 31, 2021. Key inclusion criteria included metastatic brain tumors not suitable for focal treatment, WBRT naivety, age 20 to 75 years, and at least 1 measurable brain metastatic lesion. The primary end point was brain-specific PFS, with an expected hazard ratio of 0.60, a 2-sided α ≤ .20, and power of 0.8. Eligible patients were randomly assigned at a ratio of 2:1 to the experimental arm, which involved 3 cycles of BEEP followed by WBRT, or the control arm, which involved WBRT alone. The primary end point was the determination of brain-specific PFS by local investigators according to the Response Evaluation Criteria in Solid Tumors, version 1.1, the initiation of other brain-directed treatment after WBRT, or death. Other key end points included brain-specific objective response rate after 8 weeks of BEEP treatment or WBRT and 8-month brain-specific PFS rate, PFS, and overall survival. A total of 118 patients with BMBC were randomized, with the intention-to-treat cohort comprising 112 patients. The median age was 56 years (range, 34-71 years), and 61 patients (54.5%) had ERBB2 (formerly HER2 or HER2/neu)-positive disease. The median (range) brain-specific PFS was 8.1 (0.3-29.5) vs 6.5 (0.9-25.5) months in the experimental and control arms, respectively (hazard ratio, 0.71; 95% CI, 0.44-1.13; P = .15; significant at predefined α ≤ .20). The brain-specific objective response rate at 2 months was not significantly different (BEEP treatment vs WBRT, 41.9% vs 52.6%), but the 8-month brain-specific PFS rate was significantly higher in the experimental group (48.7% vs 26.3%; P = .03). Adverse events were generally manageable with prophylactic granulocyte colony-stimulating factor treatment. The findings show that induction BEEP before WBRT may improve the control of BMBC compared with using upfront WBRT, which could address an unmet need for an effective systemic treatment for intractable brain and extracranial metastases from metastatic breast cancer. ClinicalTrials.gov Identifier: NCT02185352.

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.

A Prospective, Exploratory, Phase II Study of the Xpo-1 Inhibitor Selinexor in Combination with RCHOP in Double/Triple-Hit Large B-Cell Lymphoma

Background Double-hit (DH) lymphoma or triple-hit (TH) lymphoma, according to 2016 WHO Classification Criteria, is recognized as a distinct subset of non-Hodgkin lymphoma. The optimal treatment for DH/TH lymphoma remains unclear, although outcomes are inadequate with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) alone. Selinexor is a first-in-class, oral therapeutic that forms a slowly reversible covalent bond with cytoplasm by exportin 1 (XPO1/CRM1), leading to its inactivation. The U.S. Food and Drug Administration has approved selinexor monotherapy for relapsed/refractory DLBCL. Previous studies also suggested that selinexor was used to treat 5 patients with relapsed/refractory DH lymphoma, and 1 patient achieved CR and 2 achieved PR. Here, we report on the efficacy and safety of selinexor in combination with RCHOP as first-line treatment in patients with DH or TH lymphoma. Methods This prospective, phase 2, exploratory study was conducted in Zhejiang Cancer Hospital. The primary endpoint of the study was to evaluate the objective response rate (ORR), including complete remission (CR) rate and partial remission (PR) rate. In addition, diagnostic tumor tissue was prepared to conduct NGS analysis, and dynamic peripheral blood samples were collected before treatment, after 4 cycles when achieving CR from first-line chemotherapy, and progression of disease, to conduct ctDNA analysis. The initial dose of each drug in this regimen is as follows (repeat every 21 days, 6 cycles in total): rituximab: 375mg/m 2, d0; vindesine 4mg, d1; epirubicin 75mg/m 2, d1 (or liposomal doxubicin 35mg/m 2, d1); cyclophosphamide: 750mg/m 2, d1; prednisone: 100mg, d1-5; selinexor 60mg orally once a week. AEs were assessed according to the National Cancer Institute Common Terminology Criteria (CTCAE, version 4.0). Results From May, 2022, 8 patients were enrolled in the study, including 5 females and 3 males. All patients had received at least 2 cycles of selinexor with RCHOP. A full summary of patient baseline characteristics and response to chemotherapy was shown in Table 1. Four patients have completed full cycles of chemotherapy, while 2 patients are still undergoing treatment, and 2 patients suspended subsequent chemotherapy due to rejection of antitumor treatment. A total of 34 cycles of chemotherapy have been completed. Best responses after induction as assessed by positron emission tomography/CT were 5 CRs and 3 PRs. Two patients received ASCT as consolidation therapy after achieving CR. CNS prophylaxis with intrathecal methotrexate was administered to all patients for 2-6 cycles. No patient experienced disease progression, and no patient had CNS involvement during follow-up period (Figure 1A). All patients were assessable for toxicity. All patients in the study received prophylactic granulocyte colony-stimulating factor after each cycle of chemotherapy. The most common hematologic toxicities included anemia (15/34, 44.1%), neutropenia (20/34, 58.8%), thrombocytopenia (13/34, 38.2%), leukopenia (10/34, 29.4%). Other nonhematologic toxicities included fever (6/34, 17.6%), nausea (16/34, 47.1%), vomiting (13/34, 38.2%), fatigue (20/34, 58.9%), and infection (5/34, 14.7%). NGS was conducted successfully in 3 patients, while another 5 patients could not provide NGS data due to insufficient tumor tissue. 139 somatic alterations were detected in 3 patients, with a median of 30 mutations per sample. BCL6/IGLL5/TMSB4X were the most frequently mutated gene in 100% of patients followed by 66.7% who had BTG2/ETS1/EZH2/MYC/NFKBIE/OSBPL10/SOCS1/TNFRSF14 mutations. TP53 mutations were detected in 33.3% of the patient (Figure 1B). In 71.4% (5/7) of the cases, we were able to detect a total of 143 variants in the ctDNA from pretreatment serum samples. 80 variants were detected in both tumor tissue and peripheral blood samples. 4 variants were detected only in the ctDNA, and 59 were detected only in the tissue biopsy. Serial ctDNA monitoring results showed that 100% (8/8) reduction to zero in ctDNA after 4 cycles of chemotherapy. Conclusions Selinexor combined with RCHOP may be an effective first-line regimen for patients with DH/TH lymphoma. Dynamic testing of ctDNA demonstrated deep remission to chemotherapy. Based on the encouraging results of the current study, a large scale, multicenter trial is needed to further investigate this promising regimen.

Detection of factors related to treatment reduction in docetaxel and ramucirumab for non-small cell lung cancer treatment

Treatment using docetaxel (DOC) and ramucirumab (RAM) is an effective regimen in second or later line advanced non-small cell lung carcinoma (NSCLC) treatment. However, it induces severe adverse effects, resulting in treatment reduction such as dose reduction and/or discontinuation. This study aimed to reveal the factor(s) associated with treatment reduction in DOC + RAM. We retrospectively evaluated patients with advanced NSCLC (n = 155). Treatment reduction of the second course due to severe adverse effects was conducted in 25.8% of the participants, and relative dose intensity at the second course was 95.7 ± 8.4% for DOC and 91.9 ± 24.8% for RAM. Multivariate logistic regression analyses identified that baseline anemia and prophylactic granulocyte colony-stimulating factor (G-CSF) administration are preventive factors for the reduction (adjusted odds ratio, 0.29; 95% confidence interval, 0.12–0.66; P = 0.004 for baseline anemia, 0.18; 0.08–0.42; P < 0.0001 for prophylactic G-CSF administration). The primary cause of the reduction was febrile neutropenia, and the same factors were identified. Our study revealed that patients with baseline anemia and prophylactic G-CSF administration have less risk for treatment reduction in DOC + RAM for NSCLC treatment.

Assessment of hospitalizations and cytopenia events among patients with extensive stage small cell lung cancer (ES-SCLC) receiving chemotherapy with trilaciclib.

531 Background: Prior studies have reported that that nearly 75% of patients receiving chemotherapy for small cell lung cancer present a hospitalization associated with myelosuppression. Trilaciclib is a myeloprotective agent indicated for use prior to chemotherapy in ES-SCLC. Given the relative recency in trilaciclib approval (2/12/2021), this study assessed real-world outcomes associated with trilaciclib among patients with ES-SCLC. Methods: This study was a retrospective analysis of adult ES-SCLC patients diagnosed between 2020 and 2023 using the 100% Medicare Fee-for-Service and MORE2 Registry claims databases. Eligible patients met literature-based criteria for ES-SCLC using International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes, received platinum/etoposide- or topotecan-based chemotherapy regimens after diagnosis, and were continuously enrolled ≥ 30 days preceding and following chemotherapy initiation. Patients were categorized into 2 mutually exclusive cohorts: 1) trilaciclib administered at chemotherapy initiation and with no granulocyte colony stimulating factor (G-CSF) received during chemotherapy, and 2) no trilaciclib administered during chemotherapy. Chi-square tests and student’s t-tests were used to assess statistically significant differences between groups on cytopenia events (based on the appearance of an ICD-10 diagnosis code) and all-cause hospitalizations during the post-index period. Data use agreements prohibit reporting of categorical outcomes of &lt; 11 patients. Results: 132 trilaciclib (mean age 70.6, male 50.8%) and 12,305 non-trilaciclib patients (age 68.0, male 48.2%) were eligible for the study; median follow-up was 202 days. Compared to the non-trilaciclib cohort, patients receiving trilaciclib had a lower rate of hospitalizations per patient per month during follow-up (0.14±0.25 vs. 0.19±0.27; p &lt;0.001). Within 90 days post-chemotherapy initiation, trilaciclib was associated with lower rates of hospitalization (21.2% vs. 32.4%; p &lt;0.01) and febrile neutropenia (&lt; 3% vs. 5.7%, p=0.01). Anemia (44.7% vs. 52.6%, p=0.07), neutropenia (9.1% vs. 14.9%, p=0.06) and thrombocytopenia (5.3% vs. 8.4%, p=0.2) were numerically lower for trilaciclib patients in the 90-day post-index period. Results were similar when the non-trilaciclib group was stratified by prophylactic G-CSF usage. Conclusions: This real-world study demonstrated that receiving trilaciclib prior to chemotherapy treatment was associated with a lower rates of hospitalizations and cytopenia events, suggesting trilaciclib may prevent adverse events associated with treatment for ES-SCLC.

Predictors of the development of febrile neutropenia in chemotherapy for advanced germ cell tumors.

To identify the predictive factors for the development of febrile neutropenia (FN) in the course of chemotherapy for patients with germ cell tumors. From January 2005 to December 2018, 80 patients were treated with induction chemotherapy for advanced germ cell tumors at Kanagawa Cancer Center Hospital, Japan. Of these, we retrospectively analyzed 267 cycles of chemotherapy. The incidence of FN was used as the objective variable. As predictive factors, we analyzed age, international germ cell consensus classification (IGCCC), laboratory data at the start of chemotherapy in each cycle, length of the largest metastatic lesion, number of cycles, and prophylactic use of granulocyte colony stimulating factor (G-CSF). We finally analyzed 267 cycles in 78 patients. The median age was 36 years (15-64). There was a total of 267 cycles. FN occurred in 40 cycles (15%) in 31 patients (40%). The first cycle was accompanied by a significantly higher FN than the subsequent cycles (p < 0.001). The univariate analysis identified age ≧36 years (p = 0.001), creatinine clearance (CCr) <70 (p < 0.001), serum albumin <3.3 (p = 0.002), maximum tumor diameter ≧60 mm (p = 0.036), and first cycle as significant risk factors. The multivariate analysis identified age, CCr, and first cycle as independent predictive factors of FN development. We identified older age, renal dysfunction, and first cycle of chemotherapy as predictive factors for FN. No statistically significant difference was shown in the usage of prophylactic G-CSF. Special attention should be given to FN in patients with high-risk factors.

Biweekly vs Triweekly Cabazitaxel in Older Patients With Metastatic Castration-Resistant Prostate Cancer

Many patients 65 years or older with metastatic castration-resistant prostate cancer (mCRPC) are denied taxane chemotherapy because this treatment is considered unsuitable. To determine whether biweekly cabazitaxel (CBZ), 16 mg/m2 (biweekly CBZ16), plus prophylactic granulocyte colony-stimulating factor (G-CSF) at each cycle reduces the risk of grade 3 or higher neutropenia and/or neutropenic complications (eg, febrile neutropenia, neutropenic infection, or sepsis) compared with triweekly CBZ, 25 mg/m2 (triweekly CBZ25), plus G-CSF (standard regimen). A total of 196 patients 65 years or older with progressive mCRPC were enrolled in this prospective phase 3 randomized clinical trial conducted in France (18 centers) and Germany (7 centers) between May 5, 2017, and January 7, 2021. All patients had received docetaxel and at least 1 novel androgen receptor-targeted agent. Patients were randomly assigned 1:1 to receive biweekly CBZ16 plus G-CSF and daily prednisolone (experimental group) or triweekly CBZ25 plus G-CSF and daily prednisolone (control group). The primary end point was the occurrence of grade 3 or higher neutropenia measured at nadir and/or neutropenic complications. Among 196 patients (97 in the triweekly CBZ25 group and 99 in the biweekly CBZ16 group), the median (IQR) age was 74.6 (70.4-79.3) years, and 181 (92.3%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median (IQR) follow-up duration was 31.3 (22.5-37.5) months. Relative dose intensities were comparable between groups (median [IQR], 92.7% [83.7%-98.9%] in the triweekly CBZ25 group vs 92.8% [87.0%-98.9%] in the biweekly CBZ16 group). The rate of grade 3 or higher neutropenia and/or neutropenic complications was significantly higher with triweekly CBZ25 vs biweekly CBZ16 (60 of 96 [62.5%] vs 5 of 98 [5.1%]; odds ratio, 0.03; 95% CI, 0.01-0.08; P < .001). Grade 3 or higher adverse events were more common with triweekly CBZ25 (70 of 96 [72.9%]) vs biweekly CBZ16 (55 of 98 [56.1%]). One patient (triweekly CBZ25 group) died of a neutropenic complication. In this randomized clinical trial, compared with the standard regimen, biweekly CBZ16 plus G-CSF significantly reduced by 12-fold the occurrence of grade 3 or higher neutropenia and/or neutropenic complications, with comparable clinical outcomes. The findings suggest that biweekly CBZ16 regimen should be offered to patients 65 years or older with mCRPC for whom the standard regimen is unsuitable. ClinicalTrials.gov Identifier: NCT02961257.

A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC Neutropenia, Infection, and Myelosuppression Study Group initiative

PurposeLimited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10–20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice.MethodsThis prospective, real-world, observational, multinational, multicenter study (December 2016–October 2019) recruited patients with solid tumors or Hodgkin’s/non-Hodgkin’s lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration).ResultsIn total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2–3, and 1% in cycles 4–6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia.ConclusionsOverall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician’s judgement.

Tenosynovial giant cell tumor: a case report

BackgroundThis case reports the synchronous diagnosis of two rare unrelated diseases; leiomyosarcoma and tenosynovial giant cell tumor of the knee. It focuses on the challenges of diagnosing tenosynovial giant cell tumor, including cognitive biases in clinical medicine that delay diagnosis. It also demonstrates the pathogenic etiology of tenosynovial giant cell tumor, evidenced by the transient deterioration of the patients’ knee symptoms following the administration of prophylactic granulocyte colony-stimulating factor given as part of the chemotherapeutic regime for leiomyosarcoma.Case presentationA 37-year-old Caucasian man presented with a left groin lump and left knee pain with swelling and locking. Investigations including positron emission tomography-computed tomography and biopsy revealed leiomyosarcoma in a lymph node likely related to the spermatic cord, with high-grade uptake in the left knee that was presumed to be the primary site. His knee symptoms temporarily worsened each time granulocyte colony-stimulating factor was administered with each cycle of chemotherapy for leiomyosarcoma to help combat myelosuppressive toxicity. Subsequent magnetic resonance imaging and biopsy of the knee confirmed a tenosynovial giant cell tumor. His knee symptoms relating to the tenosynovial giant cell tumor improved following the completion of his leiomyosarcoma treatment.ConclusionsTenosynovial giant cell tumor remains a diagnostic challenge. We discuss the key clinical features and investigations that aid prompt diagnosis. The National Comprehensive Cancer Network clinical practice guidelines for soft tissue sarcoma have recently been updated to include the pharmacological management of tenosynovial giant cell tumor. Our case discussion provides an up-to-date review of the evidence for optimal management of patients with tenosynovial giant cell tumor, with a particular focus on novel pharmacological options that exploit underlying pathogenesis.

The Effect of Granulocyte Colony-Stimulating Factor (G-CSF) on Early Complications and Graft-Versus-Host Disease (GVHD) in Allogeneic Stem Cell Transplantation (ASCT) Recipients.

Objectives Granulocyte colony-stimulating factor (G-CSF) is commonly used to accelerate neutrophil recovery after allogeneic stem cell transplantation (ASCT) in most transplant centers. There was no consensus on the optimal use of G-CSF after ASCT. Although we useG-CSF to minimize morbidity and mortality, G-CSF can increase the risk of graft-versus-host disease (GVHD). In our study, we want to show the effect of prophylactic G-CSF on infection frequency, neutrophil and platelet engraftment, the duration of neutropenia, the development of GVHD, hospitalization time, and transplant-related mortality (TRM) after ASCT. Materials and methods One hundred (71 males and 29 females) patients who did not receive G-CSF and 100 (58 males and 42 females) patients who received prophylactic G-CSF were included in the study. Results Age, diagnosis, the time between diagnosis and transplantation, preparation regimen, donor type, and the number of infused cluster of differentiation (CD) 34+ cells were not different in both groups (p>0.05). The frequency of female patients was higher in the group receiving G-CSF. Febrile neutropeniawas more frequent in patients who did not receive G-CSF. Neutrophil engraftment and platelet engraftment were detected longer in patients not receiving G-CSF. The frequency of veno-occlusive disease (VOD) and hyperacute, chronic, andacute GVHD was not different in both groups (p>0.05). One hundred-day TRMand five-year overall survival (OS) were similar in the two groups (p>0.05). Conclusions Our study supports that G-CSF usage does not cause an increase in the frequency of GVHD and has a positive effect on the process by accelerating myeloid engraftment. In light of the data in our study, we can say that the use of G-CSF should be investigated in a randomized controlled clinical trial.

Impact of treatment experience on patient knowledge of colony-stimulating factors among patients receiving cancer chemotherapy: evidence from S1415CD-a large pragmatic trial.

Primary prophylactic granulocyte colony-stimulating factors (PP-CSFs) are prescribed alongside chemotherapy regimens that carry a significant risk of febrile neutropenia (FN). As part of S1415CD, a prospective, pragmatic trial evaluating the impact of automated orders to improve PP-CSF prescribing, we evaluated patients' baseline knowledge of PP-CSF and whether that knowledge improved following the first cycle of chemotherapy. Adult patients with breast, colorectal, or non-small-cell lung cancer initiating chemotherapy were enrolled in S1415CD between January 2016 and April 2020. Eight questions assessing knowledge of CSF indications, risks, benefits, and out-of-pocket costs were included in a baseline survey and in a follow-up survey at the end of the first cycle of chemotherapy. Responses were stratified by the trial arm and whether chemotherapy was low, intermediate, or high FN risk. Of the 3605 eligible patients, 3580 (99.3%) completed the baseline survey, and 3420 (95.5%) completed the follow-up survey. At baseline, 803 (22.4%) patients responded "Don't know" to all 8 questions, and all patients averaged 2.75 correct questions. At follow-up, knowledge increased by 0.34 in the high-FN-risk group (p < 0.001) but declined for the other FN-risk groups. In multivariate analysis, receiving a high-FN-risk regimen and younger age were significantly associated with knowledge improvement. Chemotherapy patients had poor knowledge of PP-CSF that improved only modestly among recipients of high-FN-risk chemotherapy. Further efforts to inform patients about the risks, benefits, and costs of PP-CSF may be warranted, particularly for those in whom prophylaxis is indicated. NCT02728596, April 6, 2016.

Real-World Impact of Prophylactic Growth Factor Use on Timing of Febrile Neutropenia and Infection After High-Risk Chemotherapy.

Prophylactic growth-factor therapy with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients with breast cancer initiating myelosuppressive chemotherapy. However, little is known about the protective benefit early in the chemotherapy cycle. To assess the relationship between G-CSF prophylaxis and incidence of FN/infection in week 1 versus beyond week 1 of the first chemotherapy cycle, a retrospective study was conducted using Medicare claims from 2005 through 2020 among patients with breast cancer initiating high-risk chemotherapy. Two cohorts were compared based on G-CSF prophylaxis within 3 days following chemotherapy initiation. The primary outcome was FN or infection, defined as hospitalization with neutropenia, fever, or infection diagnosis. Secondary outcomes were a stricter definition of FN and infection-related hospitalization. Unadjusted and regression-adjusted proportions of patients experiencing each outcome during week 1 versus beyond week 1 of the first chemotherapy cycle were compared. Of 78,810 patients meeting all inclusion criteria (>98% female; mean age, 69 years), 79% initiated TC (docetaxel/cyclophosphamide), 14% TCH (docetaxel/carboplatin/trastuzumab), and 7% TAC (docetaxel/doxorubicin/cyclophosphamide). Among patients receiving G-CSF (74%), incidence of first-cycle FN/infection was lower compared with patients not receiving G-CSF (overall, 6% vs 13%; TAC, 12% vs 19%; TC, 6% vs 12%; TCH, 5% vs 15%). However, patients who received G-CSF were generally more likely to experience FN/infection in week 1 (adjusted odds ratio [aOR], 1.24 for all; 1.73 for TAC; 1.35 for TC; and 0.76 for TCH). Results were similar for strictly defined FN (overall aOR, 1.29 for week 1 and 0.12 for beyond week 1) and infection-related hospitalization (overall aOR, 1.33 for week 1 and 0.27 for beyond week 1). Overall, the rates of chemotherapy-related FN and infection in week 1 of the first chemotherapy cycle are similar for patients receiving and not receiving G-CSF, suggesting continued risk in week 1 despite prophylactic G-CSF.

The effect of smoking on the immediate effectiveness of induction chemotherapy in the combined treatment of HPV-associated oropharyngeal cancer

Purpose. Evaluation of the effect of smoking on the immediate effectiveness (achievement of objective response – OR) of induction chemotherapy in patients receiving combined treatment for locally advanced HPV-positive squamous cell carcinoma of the oropharynx.Patients and methods. Sixty-eight patients (51 men and 17 women) with locally advanced squamous cell cancer of the oropharynx associated with papillomavirus were included in the study, which was carried out from 2021 to 2023 at the P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation and the Municipal Clinical Oncological Hospital № 1 of the Department of Health of Moscow. The patients were divided into 2 equal groups, fully comparable in terms of the main characteristics (smoking history, stage, histological type, and degree of tumour differentiation). At the first stage, patients of the 1st (main) group received de-escalated induction chemotherapy: three 21-day courses according to the TR scheme (docetaxel in the dose of 75 mg/m2 + cisplatin 75 mg/m2); patients of the 2nd (control) group were treated with standard scheme (docetaxel 75 mg/m2 + cisplatin 75 mg/m2 + 5-fluorouracil 1000 mg/m2). Patients in both groups received prophylactic granulocyte colony-stimulating factor. At the second stage, standard chemoradiotherapy was carried out against the background of drug radiomodification with carboplatin. Correlation analysis was performed by calculating the Spearman coefficient with Bonferroni correction. Differences were considered reliable at p &lt; 0.05.Results. When evaluating the objective response to treatment, it was revealed that disease control was achieved in 33 (97 %) patients from group 1 and in all 34 (100 %) patients from group 2. Complete response was observed in 3 (8.8 %) patients from group 1 and 4 (11.8 %) from group 2; partial regression in 22 (64.7 %) and 24 (70.6 %); stabilisation of the tumour process in 8 (23.5 %) and 6 (17.6 %) respectively. Further analysis showed that there was no direct or inverse correlation between smoking and differentiated level of response (primary lesion, altered lymph nodes); all patients (smokers and those who had never smoked) responded equally effectively to the first stage of combined treatment, regardless of the ICT regimen.Conclusion. In our study, no statistically significant effect of smoking on the immediate effectiveness of induction chemotherapy in the combined treatment of locally advanced HPV-associated squamous cell carcinoma of the oropharynx regardless of the induction regimen was found. However, a longer follow-up period is needed to evaluate the effect of smoking on long-term oncological outcomes.

Poor Renal Function and a High Modified Glasgow Prognostic Score Are Predictive Factors for Nedaplatin/5-Fluorouracil Combination Therapy-induced Febrile Neutropenia.

Nedaplatin (NDP)/5-fluorouracil (5-FU) combination therapy frequently causes severe neutropenia and febrile neutropenia (FN). However, there is no consensus on the risk factors for FN caused by NDP/5-FU combination therapy. Mouse models of cancer cachexia are known to be susceptible to infections. Conversely, the modified Glasgow prognostic score (mGPS) is believed to reflect cancer cachexia. We hypothesized that mGPS is a predictive factor for FN caused by NDP/5-FU combination therapy. We analyzed the relationship between mGPS and FN in patients who received NDP/5-FU combination therapy at Nagasaki University Hospital using multivariate logistic analysis. In total, 157 patients were studied, 20 of whom developed FN (12.7%). Multivariate analysis revealed that mGPS 1-2 [odds ratio (OR)=4.13, 95% confidence interval (CI)=1.42-12.02, p=0.009] and creatinine clearance <54.4 ml/min (OR=5.81, 95% CI=1.81-18.59, p=0.003) were significantly associated with the development of FN. Several guidelines suggest that patients receiving chemotherapy with an FN rate 10-20% should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF), depending on the individual patient's risk of developing FN. When NDP/5-FU combination therapy is administered to patients with risk factors identified in this study, prophylactic administration of G-CSF should be considered. In addition, the neutrophil count and axillary temperature should be monitored more frequently.