CTX Cycles Research Articles

A United Kingdom prospective, multicentre, observational cohort study investigating tolerance of anti-cancer systemic therapy in the elderly: The TOASTIE study.

1521 Background: Older adults have a higher risk of developing chemotherapy (CTx) related toxicity. The Cancer Aging Research Group (CARG) score was developed and validated in the USA to predict risk of severe CTx induced toxicity in older adults; subsequent validation studies have had varying results. The TOASTIE study sought to evaluate the CARG score prospectively in a United Kingdom (UK) population. Methods: This multicentre, prospective, observational study recruited patients aged ≥65 years commencing first-line neo-adjuvant, adjuvant or palliative CTx for any solid organ malignancy. Those receiving non-CTx agents were excluded. Baseline demographics and established frailty measures were recorded, including Eastern Cooperative Oncology Group performance status (ECOG PS), Rockwood Clinical Frailty Scale (CFS), Geriatric-8 (G8) score and Charlson Co-morbidity Index (CCI). CARG score was calculated after initial Oncology consultation. Follow-up data including CTCAEv5 toxicity and hospital admissions were collected retrospectively. Results: 19 centres recruited 330 patients between Nov 2019 - Dec 2022. Median age was 73 years (range 65-92) and 51.9% were male. 54.9% had a primary tumour of gastrointestinal origin, 48.7% received CTx with palliative intent and 70.8% received doublet therapy. At baseline, 85% patients had an ECOG PS 0 or 1, with median CFS 3 (range 0-8), G8 score 12 (range 6-16) and CCI 6 (range 2-12). Follow-up data was available for 314 (92.6%) patients; the median CTx cycles received was 4 (range 1-16) with 124 (39%) patients dose reduced at cycle one. Treatment delays occurred in 83 (26.4%) patients and 123 (39.2%) stopped treatment early, with 60 (48.8%) cases due to treatment-related toxicity. 69(22.3%) patients experienced a CTCAE grade ≥3 toxicity and 84 (27%) requiring hospital admission. CARG score was available for 313 patients; 107 (34.2%) low risk, 167 (53.4%) medium risk and 39 (12.5%) high risk. Increasing CARG risk groups had increased toxicity rates (low 19.6%, medium 22.2%, high 28.2%) however this was non-significant with no evidence of robust predictive performance (Table). The performance of CFS and ECOG PS was superior to CARG. Conclusions: In this UK older patient population, baseline frailty was prevalent. CARG score was unable to robustly discriminate or predict risk of high-grade toxicity. ECOG showed superior, albeit limited, ability to predict and discriminate toxicity risk. This study highlights the need for development of further tools predictive of toxicity in this population. [Table: see text]

Postoperative hepatic arterial chemotherapy after resection of colorectal liver metastases in patients at high risk of hepatic recurrence: A multicenter randomized phase II trial (PRODIGE 43 - PACHA-01).

3515 Background: Hepatic arterial infusion (HAI) of chemotherapy (CTx) has been proposed as a potential treatment to decrease the risk of hepatic recurrence after resection of colorectal liver metastases (CRLM). Randomized controlled trials (RCTs) led to controversial results and meta-analyses are inconclusive. We conducted a comparative phase II RCT to assess the efficacy of adjuvant HAI oxaliplatin with concomitant intravenous (IV) CTx in pts at high risk of hepatic recurrence (≥4 resected CRLM). Methods: Pts who underwent curative-intent surgery of at least 4 CRLM after preoperative IV CTx were randomly assigned (1:1) to receive adjuvant IV fluorouracil/leucovorin (LV5FU2) combined with oxaliplatin (85mg/m2) by HAI (HAI-IV arm) or IV route (IV arm) every 2 weeks, for at least 3 months to achieve a minimal duration of perioperative CTx of 6 months. The primary endpoint was the hepatic recurrence free survival (h-RFS). Secondary endpoints included the feasibility of delivering at least 4 CTx cycles, toxicity (NCI-CTCAE 4.0) including HAI catheter-related complications, RFS, overall survival (OS) and recurrence pattern. 108 randomized pts were required to detect a gain in 18-month h-RFS from 30% to 50% with a one-sided α risk of 10% and 95% power. The primary endpoint was analyzed with a Cox regression model, with adjustment for stratification factors (tumor response to preoperative CTx and number of resected CRLM). The study was prematurely stopped after randomization of 99 pts due to recruitment issues and HAI catheters market withdrawal. Results: Between Jun 2015 and Dec 2020, 99 pts (median age, 62; median number of CRLM, 5) were randomly assigned in HAI-IV arm (50 pts) or IV arm (49 pts). After a median follow-up of 56 months, the intent-to-treat analysis showed a significantly longer h-RFS in the HAI-IV arm compared to the IV arm (median 25 [16-37] vs 12 months [8-21]; HR 0.598 [95%CI 0.379-0.944], p = 0.027). 5-year h-RFS was 32% [19-45] in the HAI-IV arm vs 13% [4-27] in the IV arm, respectively. Median and 5-year OS were 74 months [51-74] and 60% [43-74] in the HAI-IV arm vs 54 months [37-69] and 46% [29-61] in the IV arm (HR 0.551 [0.299-1.015], p = 0.056). The median number of postoperative CTx cycles was 6 in both groups with 86% and 78% of patients having received at least 4 cycles in HAI-IV and IV arms (p = 0.7), respectively. Grade 3-4 toxicity rate was 58% in the HAI-IV arm vs 31% in the IV arm (p = 0.01). Overall, nine pts (18%) experienced HAI-related complications. No toxic death occurred in both arms. Conclusions: Despite a higher but acceptable toxicity, combination of HAI oxaliplatin with IV LV5FU2 significantly improved h-RFS after curative resection of CRLM in high-risk patients. This combined treatment should be considered as a valid option for these patients. Clinical trial information: NCT02494973 .

Perioperative or adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer: Quality of life results of the randomized phase II AIO-NEONAX trial.

694 Background: Perioperative chemotherapy (CTX) in resectable pancreatic adenocarcinoma (rPDAC) is still not considered SoC and data regarding efficacy but also quality of life (QoL) are limited. NEONAX is a prospective, randomized phase II trial in patients with rPDAC with two independent experimental arms examining perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m2) and nab-P (125mg/m2) on days 1,8,15 of a 28-day cycle. The primary endpoint DFS at 18 mo. as well as DFS, OS and safety have already been reported. Here we present the QoL data of the NEONAX trial. Methods: QoL was evaluated by EORTC QLQ-C30, EORTC QLQ-PAN26 and HADS-D questionnaires at baseline, at the beginning of each CTX cycle (neoadj. and adj. in arm A, only adj. in arm B), after neoadj. treatment in arm A as well as prior and post resection and after 6 cycles of CTX. Results: Global health status score (GHS-score) (QLQ-C30) showed no difference between baseline (t1) and the timepoint after 6 cycles of CTX (t2) in the perioperative arm A (66.7/100 at both timepoints). Here patients experienced the lowest GHS-score pre- and postoperatively (50/100 in both cases). Adjuvant arm B showed a deterioration in the GHS-score of 12.5 points from timepoint 1 to 2 (62.5/100 to 50.0/100). Here the lowest GHS-score was observed within 4 weeks post-surgery (41.7/100). Physical function score (QLQ-C30) was decreased by 6.7 points (86.7/100 to 80/100) in perioperative arm A and by 26.7 points (86.7/100 to 60/100) in arm B between both timepoints. Role function (QLQ-C30) was reduced by 16.7 points (83.3/100 to 66.7/100) in arm A and by 33.3 points (83.3/100 to 50/100) in arm B between both timepoints. In the remaining subscales of the used questionnaires the two arms of the trial showed comparable median scores over the whole study period. The number of submitted questionnaires at each timepoint varied but was at large comparable in both arms. Conclusions: QoL was largely preserved in the perioperative as well as the adjuvant arm of the NEONAX trial. GHS-score was lower pre-and postoperatively in arm A. The lowest GHS-score was observed postoperatively in the adjuvant arm B. QoL was restored at the end of the treatment period in the perioperative arm A and remained slightly reduced in arm B suggesting that QoL is not substantially impaired by perioperative treatment in rPDAC. Clinical trial information: NCT02047513 . [Table: see text]

Survival prediction using radiomic signatures in metastatic gastric and esophageal adenocarcinoma (GEA).

357 Background: Radiomic characterisation of tumour phenotypes can generate image-driven biomarkers that potentially aid in clinical decision-making. We sought to identify radiomic features in metastatic GEA that may be predictive for survival outcomes. Methods: A retrospective analysis between 2009-20 identified patients (pts) with metastatic GEA. All pts received chemotherapy (CTx), with a ‘baseline’ and 8-12 week ‘on-treatment’ contrast-enhanced CT chest/abdomen/pelvis performed. Radiomic analysis was performed with LIFEx (livexsoft.org). Population demographics and clinical outcomes were recorded. Univariable Cox proportional hazards model (UVA) assessed clinical variables (n=26) predictive of overall survival (OS) and progression-free survival (PFS) with p=0.05 indicating significance. Multivariable Cox model (MVA) was used to assess radiomic features (n=78) in the presence of clinical variables. Concordance index (C-index) was calculated to assess model performance (≥0.7 = high predictive accuracy). A ‘validation’ cohort analysis was performed to validate the model. Results: 166 pts were identified (primary cohort n=143; validation cohort n=23). 123 had de-novo metastatic disease, 43 recurrence following curative-intent therapy. In the primary cohort the median age was 58.1y, 101 (71%) were male, 120 (84%) were non-Asian and 131 (92%) were ECOG 0-1. Similar demographics were observed in the validation cohort. Both ‘baseline’ and ‘on-treatment’ scans UVA identified Her2 status, ethnicity, and the number of CTx cycles as predictive of PFS, while ECOG, brain metastases, neutrophil count (ANC), albumin and number of CTx cycles were predictive of OS. ‘Baseline’ model analysis for PFS and OS identified consistent radiomic features (HUskewness; HUpeakSphere), with an observed C-index 0.6 and 0.657 respectively. No radiomic features were identified on ‘on-treatment’ PFS analysis. ‘On-treatment’ OS analysis is shown in the table with 3 radiomic features (SHAPE Surface; SHAPE Compacity; PARAMS ZSpatial-Resampling) predictive for OS. The C-index is 0.76. Analysis of the validation cohort supported the model (C-index 0.815) for ‘on-treatment’ OS. Conclusions: Radiomic analysis identified a number of features associated with PFS and OS. The features specifically identified on ‘on-treatment’ scans were highly predictive for OS. Our analysis suggests radiomic features in addition to clinical variables can be predictive of outcome in patients with metastatic GEA receiving CTx.[Table: see text]

Evaluation of febrile neutropenia and myelosuppression in patients receiving FOLFOX/FOLFIRI in gastrointestinal cancer treated with same-day (SD) pegfilgrastim/pegfilgrastim-CBQV (PFG).

311 Background: The National Comprehensive Cancer Network (NCCN) guidelines and the manufacturers of PFG recommend administration at least 24 hours after chemotherapy (CTX). Administering SD PFG carries the potential risk for exacerbation of neutropenia based on analyses in lymphoma and breast cancer regimens; however, little data exists on infusional fluorouracil and SD PFG administration. The availability of biosimilar PFG and increased utilization of growth factors during the COVID-19 pandemic has led to changes in practice for SD PFG administration. This study explored the incidence of febrile neutropenia (FN) and myelosuppression with FOLFOX and FOLFIRI regimens in Gastrointestinal malignancies (GI) to address the safety of SD utilization of PFG. Methods: Patient data was extracted through electronic health records search of ICD-9 and ICD-10 codes for GI malignancies and treated with FOLFOX or FOLFIRI-based regimens from November 2013 to May 2021. SD administration was defined as administration of PFG within 15 minutes after fluorouracil pump disconnect. The primary endpoint of our study was to evaluate the incidence of FN across all CTX cycles for up to four cycles, in SD PFG administration. Secondary outcomes included chemotherapy induced neutropenia (CIN), hospitalizations, and CTX dose reduction or delay. Results: Three hundred and thirty-nine patient charts were reviewed with 55 patients meeting the inclusion criteria. In our study cohort, 72.7% received FOLFOX and 27.2% received FOLFIRI-based regimens. Out of all 194 CTX cycles, 136 (70.1%) cycles received pegfilgrastim and 58 cycles received pegfilgrastim-cbqv (29.9%). Two patients had grade 3/4 CIN (1%), with both cases resulting in FN (1%). Both FN cases resulted in hospitalizations, and dose delays or reductions. Investigation of FN incidences revealed that both patients received CTX with active infections, one case with a urinary tract infection and the other with a chronic gangrene infection. Conclusions: Our study results suggest that SD administration of PFG can be as a safe and effective alternative to 24-hour post-chemotherapy administration in patients receiving FOLFOX or FOLFIRI-based regimens. The incidence of FN was noted to be minimal in our study. Furthermore, no noted increase in myelosuppression was seen in our analysis, as compared to previous studies in breast cancer and lymphoma-based regimens. SD administration not only minimizes travel burdens on long-distance patients but also has allowed for reduction in infusion appointments and therefore possible exposure to the SARS-COV2 virus during the 2020-2021 pandemic. Future prospective studies are warranted in order to elucidate the risk of FN and myelosuppression in patients undergoing chemotherapy for GI malignancies with SD PFG administration.

Institutional chart review on same-day pegfilgrastim administration in small cell lung cancer (SCLC) patients receiving myelotoxic chemotherapy.

71 Background: Pegfilgrastim administration is recommended at least 24 hours after the end of chemotherapy (CTX) treatment for prevention of chemotherapy-induced (febrile) neutropenia (CIN/FN). Published studies have found no differences in the risk of FN between same-day and next-day pegfilgrastim administrations in certain cancers. To evaluate the efficacy and safety of same-day compared to next-day pegfilgrastim administration in SCLC patients, we evaluated our own institutional data. Methods: Using ICD-9 and ICD-10 codes for SCLC, electronic health records were reviewed retrospectivey for the period 11/1/2013-8/31/2018 at the University of Arizona Cancer Center (UACC). Inclusion criteria were age 18 or older, biopsy confirmed SCLC diagnosis, treated at UACC, and pegfilgrastim administration on the same day as CTX. Outcomes collected in the first cycle and all cycles of CTX were: FN incidence, CIN grade 3/4, and treatment delay or hospitalizations due to CIN/FN. Results: Out of 1,181 patient records, 34 patients met inclusion criteria. The median age was 67.5 years, 23.5% of patients had stage 3 or 4 SCLC while 50% had 0-1 ECOG status. 44.1% of patients had a risk based on the type of CTX. Average baseline absolute neutrophil count was 5.55x109cells/L (SD=1.27x109cells/L). A total of 104 CTX cycles were given. Outcomes are summarized in the Table below. After the first cycle, the incidence rate of CIN grade 3/4 was 5.88%, but 0% for all other outcomes. Conclusions: After the first cycle, there were s of FN and no patients experienced treatment delays or hospitalizations related to CIN/FN; only two cases for CIN grade 3/4 were observed. Across all cycles, CIN grade 3/4 was observed in 17 cycles. In only two cycles, treatment was delayed or patient was hospitalized due to CIN/FN, not involving same patients. FN was observed in only 3/104 cycles. All observed rate were comparable or lower than known rates for next-day pegfilgrastim administration. Future studies including randomized trials should be further evaluated.[Table: see text]

Quality of Life and Patient Reported Outcome (PRO) in Patients Receiving High and Moderate Emetogenic Chemotherapy (Ctx) - Results of a German Non-Interventional Study with NEPA - a Netupitant/Palonosetron Fixed Dose Combination

Introduction: NEPA is a fixed dose combination of the NK1-receptor antagonist (RA) netupitant and the 5-HT3-RA palonosetron and approved for prevention of chemotherapy-induced nausea and vomiting (CINV) in pts receiving cisplatin-based highly emetogenic (HEC) or moderately emetogenic Ctx (MEC). Data from one of the pivotal studies demonstrates the safety and efficacy of NEPA in antrazyklin (A)-cyclophosphamid based Ctx, a regime recently reclassified as HEC. Both drugs are frequently used in regimens for hematology pts. A German non-interventional study investigated NEPA's efficacy and impact on quality of life in adult cancer pts by patient-related outcomes (PRO) and physicians' personal assessment under real life conditions. Primary objective was the evaluation of quality of life (QoL) in adults receiving NEPA for CINV prevention. Secondary endpoints were efficacy and safety of NEPA.Methods: Open label, non-interventional, prospective, national, multicenter study that evaluates CINV prevention and patients' QoL with NEPA in pts receiving either HEC or MEC on up to 2 consecutive Ctx days for at least consecutive 3 cycles. QoL was evaluated by the validated FLIE questionnaires at the end of each Ctx cycle. Efficacy was documented by the treating physicians and via patient diaries for 3 Ctx cycles within 24 hours after and additional 4 days after chemotherapy. Safety, additional medication and physicians' overall satisfaction was reported via eCRF.Results: Between June 2015 and May 2017 a total of 1959 pts were enrolled with 1883 pts being eligible. 1846 pts were included in the efficacy analysis in the 1st, 1711 pts in the 2nd and 1600 pts in the 3rd cycle. Median age was 57 (range of 28-89). 55% received anthracyclin-based and 31% platinum based Ctx. Efficacy, evaluated by physicians' personal assessment on a 4-point scale, was rated very good or good for 1656 (89.7%), 1540 (90.0%) and 1469 (91.8%) patients in cycle 1, 2 and 3, respectively. At this stage, PRO with complete response was analyzed based on 293 completed diaries. Here, 83.9% reported no emesis and no rescue medication in the acute phase (0-24h post chemotherapy), while 78.5% and 74.0% reported complete response in the delayed (>24-120h post chemotherapy) and overall phase (0-120h post chemotherapy). A high percentage of patients did not suffer from any emesis (94%, 94% and 90% in the acute, delayed and overall phase, respectively). Over 90% of pts reported no impact on daily QoL due to vomiting in all 3 cycles with HEC or MEC.Conclusions: NEPA proved to be highly effective for prevention of CINV. Patient reported outcome was rated very good or good in more than 90% of patients in all three reported Ctx cycles in the acute as the delayed phase of highly and moderately emetogenic Ctx including platinum or anthracyclin based therapy. The physicians evaluation was concordant to PRO. DisclosuresKarthaus:HELSINN: Honoraria, Other: Travel grant; Riemser: Honoraria, Other: Travel grant. Schilling:Riemser: Honoraria, Other: Travel grant.

Evaluation of same day pegfilgrastim (PFG) or PFG-cbqv prophylaxis of chemotherapy induced (Febrile) neutropenia (CIN/FN) in bendamustine plus rituximab (BR) and CHOP+/-R regimens in patients with lymphoma and chronic lymphocytic leukemia (CLL): Real-world, single-center experience.

e19541 Background: BR and CHOP+/-R regimens are considered an intermediate FN risk (10-20%) per guidelines. Patients (pts) receiving these regimens need to be assessed for FN prophylaxis using specific risk factors. Current guidelines suggest waiting 24 hours post chemotherapy (CTX) to administer PFG due to an increased FN risk. Studies have shown equivocal outcomes between same day (D1) and next day (D2) administration. We evaluated real-world outcomes associated with D1 and D2 PFG administration in pts with lymphoma and CLL treated with these two regimens. Methods: Retrospective chart review of lymphoma or CLL pts treated with CHOP+/-R or BR and PFG or a biosimilar from 11/2013 through 11/2020 at the University of Arizona Cancer Center was conducted. Two pt cohorts were analyzed based on D1 vs D2 PFG administration timing. Outcomes of interest were the incidence of FN across all CTX cycles and after cycle 1, CIN grade 3/4, hospitalizations, antibiotics administration, and CTX dose reduction or delay. A secondary analysis compared the incidence of FN in pts receiving CHOP+/-R in our study with published studies (Burris et al, 2010 and Cheng et al, 2014) of D1 PFG in lymphoma pts. Results: Of the 116 pts meeting inclusion criteria, 103 received PFG on D1 and 13 on D2 of CTX. As shown in the Table, the incidence of 1st cycle FN was 6% vs 8% (P>0.05), FN across all cycles was 4% vs 5% (P>0.05), CIN grade 3/4, hospitalization, anti-biotic administration and dose delays/reductions incidences were 11% vs 16% (P>0.05), 8% vs 11% (P>0.05), 6% vs 32% (P=0.001), 11% vs 5% (P>0.05) for D1 vs D2, respectively. The incidence of 1st cycle FN in D1 cohort was 6% vs 19% (P=0.15) and 11% (P=0.67) in our study vs Burris et al and Cheng et al, respectively. While the incidence of FN across all cycles in D1 group was 5% vs 9% (P=0.03) and 17% (P=0.001) in our study vs Burris et al and Cheng et al, respectively. Conclusions: This data provides evidence that D1 PFG/PFG-cbqv does not increase FN or delayed engraftment risk as compared to previously published studies in lymphoma and may be safe to use after CTX has been administered.[Table: see text]

Cost-efficiency analysis of conversion from reference pegfilgrastim to its biosimilar (pegfilgrastim-jmdb) and expanded access to food and transportation support for Medicare/Medicaid patients within the CMS Oncology Care Model.

e18837 Background: The CMS Oncology Care Model (OCM) aims to improve quality of care and health outcomes in cancer centers at the same or lower cost. We performed cost-efficiency analyses of converting selected cancer patients (pts) from reference pegfilgrastim (PFG) to its biosimilar (PFG-jmdb); and simulated re-allocating savings to provide nutrition and transportation support to CMS beneficiaries within OCM. Methods: Incidence rates for breast, ovarian, lung, colorectal cancers and non-Hodgkin lymphoma were extracted from SEER, further stratified by age <65 (commercial insurance) or >65 (Medicare) adjusted for Medicare/Medicaid mix. Chemotherapy (CTX) rates were matched to tumor type; of these 19.4% were assumed to require PFG prophylaxis (PPX). Two models compared respectively prefilled syringe (PFS) and on-body injector (OBI) reference PFG to PFS PFG-jmdb. Cost inputs included Average Sales Price (ASP) 3Q20 for Medicare and National Average Drug Acquisition Cost (NADAC, estimated by wholesale acquisition cost (WAC)-3.9%) for Medicaid pts plus medication administration. Cost savings across various biosimilar conversion rates for CTX cycles 1-6 were translated into $100 units of healthy food or medical transportation. Results: In 2020, biosimilar conversion for the estimated 31,210 Medicare and 1,722 Medicaid pts in the 5 tumor types needing PFG PPX yielded savings of up to ̃$19M (Medicare) and ̃$20M (Medicaid). These savings could have provided a monthly $100 food or transportation check to at least 24,716 Medicare or 33,630 Medicaid pts for 6 months. Conclusions: Savings from biosimilar conversion can be re-allocated on a budget neutral basis to food and transportation support to pts with such needs. This achieves the dual OCM aim of reducing drug budgets while enhancing patient-centric support services.[Table: see text]

An institutional evaluation of the safety and efficacy of same-day administration of pegfilgrastim in patients receiving chemotherapy for lung cancer.

e18591 Background: Pegfilgrastim is recommended to be administered 24 hours after myelosuppressive chemotherapy (CTX) as prophylaxis for chemotherapy-induced (febrile) neutropenia (CIN/FN). Recent studies have yielded equivocal data on same day versus next day administration of pegfilgrastim. There has been limited real world evidence addressing lung cancer (LC) patients and the use of same day pegfilgrastim. We evaluated our own institutional data on the safety of same day pegfilgrastim administration in LC patients. Methods: A retrospective chart review was performed by searching electronic health records using ICD-9 and ICD-10 codes corresponding with a lung cancer diagnosis between November 1, 2013 and August 31, 2018 at The University of Arizona Cancer Center (UACC). Patients included in the study were 18 years of age or older, diagnosed with biopsy-confirmed lung cancer, treated at UACC, and receiving chemotherapy and pegfilgrastim on the same day. The outcomes of interest included FN incidence after the first cycle and across all cycles of CTX, CIN grade 3/4 and CTX dose delays or hospitalizations due to CIN/FN after first cycle and across all cycles of CTX. Results: 1,181 patient records were reviewed and 114 patients met the inclusion criteria; 87 (76%) patients had non-small cell LC and 27 (24%) patients had small cell LC. The median age was 68 years, 52% of patients had cancer stage of 3 to 4, and 63% of patients had 0-1 ECOG status. The FN risk assessment was mild in 72% of patients. The mean (SD) of baseline absolute neutrophil count was 5.68 (3.09). In total 384 CTX cycles were received. The table shows the results of all intended outcomes. One patient experienced FN after the first cycle of CTX of irinotecan and 5 patients developed 6 FN episodes across all cycles; 2 patients were on carboplatin etoposide; 1 patient on cisplatin etoposide; 1 patient on vinorelbine and 1 patient was on pemetrexed and then on irinotecan CTX when the two FN episodes were developed. Conclusions: This study showing that same day administration of pegfilgrastim was as effective as next day administration in LC patients, without warranting any concerns for febrile neutropenia or delayed engraftment. Utilization of same day pegfilgrastim, in light of biosimilars and COVID, provides a unique opportunity for cancer care without concerns for FN as stated in previous studies.[Table: see text]

Patient, nurse, and physician preferences: final results of the CONVENIENCE study evaluating pegfilgrastim prophylaxis via pre-filled syringe or on-body injector in cancer patients

PurposeThe on-body injector (OBI) automatically delivers pegfilgrastim the day after chemotherapy (CTx), thus eliminating the need of return visits to the medical office for guideline-compliant pegfilgrastim administration. The CONVENIENCE study aimed to evaluate patient, nurse, and physician preferences as well as health economics for pegfilgrastim administration either with OBI or manually using a pre-filled syringe (PS).MethodsPatients with early breast cancer, receiving two or three weekly anthracycline/cyclophosphamide or three weekly taxane-based CTx, and patients with Non-Hodgkin lymphoma (NHL) receiving first-line R-CHOP-14 or -21 were randomized 1:1 to receive both pegfilgrastim application forms for four consecutive CTx cycles in an alternating sequence starting either with OBI or PS. Primary endpoint was patient preference, assessed by questionnaires.ResultsA total of 308 patients were evaluable in the per-protocol analysis. Patients slightly preferred OBI over PS (OBI, n = 133, 43.2%; vs. PS, n = 111, 36.0%; p-value = 0.159), while study nurses slightly preferred PS (n = 19, 46.3%) over OBI (n = 18, 43.9%) and physicians clearly preferred PS (n = 24, 58.8%) over OBI (n = 15, 36.6%). Among patients with preference for OBI, saving of time was their major reason for preference (53.4%). Pegfilgrastim was administered 24–72 h after each CTx cycle in 97.6% of OBI and 63.1% of PS applications.ConclusionThe OBI was slightly preferred by patients and saving time was the major reason for their preference. PS was physicians’ most preferable choice and slightly preferred by nurses. Using OBI, pegfilgrastim was almost always administered within the time period recommended by current guidelines, while it was often not applied as specified using PS.Trial registrationNo: ClinicalTrials.gov No. NCT03619993. Registered on June 25, 2018

Analysis of Quality-of-Life (QoL) in Patients Receiving NEPA for Prevention of Chemotherapy-Induced Nausea (CINV) and Vomiting

Introduction: Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect that has a detrimental impact on QoL. For pts receiving highly emetogenic chemotherapy (HEC), which includes those on anthracycline-cyclophosphamide (AC)-based regimens, a triple combination of a neurokinin-1 receptor antagonist (NK1 RA), a 5-hydroxytryptamine-3 (5-HT3) RA and dexamethasone is recommended by the NCCN and MASCC/ESMO. The complexity of the NK1 RA-based schedules may be a reason for the low adherence to antiemetic guidelines and a not sufficient control of CINV in pts receiving HEC and MEC. NEPA is the only available fixed-combination antiemetic. It is composed of an NK1 RA, netupitant (300 mg) and a 5-HT3 RA, palonosetron (0.50 mg); thus, it acts by blocking two main emetic pathways in a single dose and eases compliance to guidelines. Methods: Prospective, non-interventional study at 162 sites in Germany from 09/2015 to 03/2018. The aim was to determine QoL of adult cancer pts receiving NEPA for the prevention of nausea and vomiting associated with 1 or 2 day HEC or MEC in daily clinical practice. The primary outcome was measured via the Functional Living Index-Emesis (FLIE) questionnaire. FLIE questionnaires were analyzed according to the FLIE scoring and administration manual v12; higher scores correlated to better performance on daily life activities due to the lower occurrence of nausea and vomiting. 'No impact on daily life (NIDL) activities' for individual nausea and vomiting domains was defined as a FLIE score higher than 53.8; NIDL for the combined domains of nausea and vomiting was defined as a FLIE score higher than 108. Secondary objectives included evaluating effectiveness, as determined by measuring the rate of complete response (CR) and rescue medication, as well as safety outcomes. Efficacy was documented by the treating physicians and via patient diaries for 3 Ctx cycles within 24 hrs and on 4 additional d after Ctx. Safety, additional medication and physicians' overall satisfaction was reported via eCRF. Results: A total of 2429 pts were enrolled, 2405 of whom were assessed for eligibility; of these, 2173 were included in the final analysis and constitute the full analysis set population (FAS). Evaluable FLIE questionnaires were collected from 1886 (88%) pts in cycle 1, 1795 (88%) pts in cycle 2 and 1698 (86%) pts in cycle 3. A total of 1389 pts received HEC and 764 MEC in cycle 1. The majority of pts (91%) were scheduled to receive 1-day ctx at study entry. More than half of the pts (1230, 56%) received anthracycline/cyclophosphamide-(AC), 19% carboplatin-, 8% cisplatin-, 7% oxaliplatin- and 9% other CTs. NIDL due to vomiting during cycle 1 was reported by 84% of pts in the HEC group and 82% in the MEC group. These frequencies were maintained in cycles 2 and 3. NIDL due to nausea increased from 54% in cycle 1 to 58% in cycle 3 for pts receiving HEC, and from 59% in cycle 1 to 66% in cycle 3 for pts in the MEC group. The rates for the combined domain of NIDL due to nausea and vomiting were consistent across cycle 1 (64%) and in cycles 2 and 3 (66% in each cycle) for pts in the HEC group, while the rates increased from 67% in cycle 1 to 73 and 74% in cycles 2 and 3, respectively, for pts receiving MEC. The CR rate (no emesis and no use of rescue medication) was 89% in the acute phase (0-24 h), 87% in the delayed phase (25-120 h) and 83% in the overall period (0-120 h) in cycle 1. The no significant nausea (NSN) rate was 79 % in the acute, 75 % in the delayed and 67 % in the overall phase in cycle. The majority of physicians (≥89%) and pts (≥86%) rated the effectiveness of NEPA prophylaxis as 'very good' or 'good' during all three ctx cycles. The most common NEPA-related AEs, which occurred in >1% of pts in the overall study period, were fatigue (3%), constipation (3%), nausea (2%) and insomnia (2%). There were no reports of NEPA-related deaths. Conclusions: Real-life data show that NEPA was effective in the prevention of chemotherapy-induced nausea and vomiting in cancer patients. NEPA had beneficial effects on the quality of life and was highly effective in the acute and delayed phase of HEC and MEC. NEPA antiemetic effectiveness was rated highly both by patients and physicians. Disclosures Karthaus: RIEMSER: Consultancy, Honoraria. Schilling:Riemser: Honoraria.

Stable Symptom Clusters and Evolving Symptom Networks in Relation to Chemotherapy Cycles

ContextThe existence of stable symptom clusters with variations or changes in cluster membership and the merging of symptom clusters over time urge us to investigate how symptom relationships change over time. ObjectivesTo identify stable symptom clusters and understand networks among symptoms using longitudinal data. MethodsSecondary data analysis was conducted using data from a nonblinded randomized clinical trial, which evaluated the effect and feasibility of the developed cancer symptom management system. For the present study, data from all participants of the original trial were analyzed (N = 249). The severity of 20 symptoms was measured before the start of chemotherapy (CTx) and during the initial four cycles of CTx. Symptom clusters were identified using principal component and hierarchical cluster analyses, and network analysis was used to explore the relationships among symptoms. ResultsThree common symptom clusters were identified. The first cluster consisted of anxiety, depression, sleep disturbance, pain, and dyspnea. Fatigue, difficulty concentrating, and drowsiness formed a second stable cluster throughout the CTx cycles. The third cluster comprised loss of appetite, taste change, nausea, and vomiting. In terms of the symptom networks, close relationships were recognized, irrespective of symptom severity level, between anxiety and depression, fatigue and drowsiness, and loss of appetite and taste change. Fatigue was the most central symptom with the highest strength. Edge thickening after starting CTx demonstrated evolving symptom networks in relation to CTx cycles. ConclusionStable symptom clusters and evolving networks were identified. The most central symptom was fatigue; however, the paucity of studies that investigated symptom networks and central symptoms calls for further investigations on these phenomena. Identification of central symptoms and underlying mechanisms will guide efficient symptom management. Future studies will need to focus on developing comprehensive interventions for managing symptom clusters or targeting central symptoms.

PCN192 INCIDENCE OF FEBRILE NEUTROPENIA AND ENVIRONMENTAL FACTORS OBSERVED WITH OPTIMAL RECEIPT OF PEGFILGRASTIM VIA ON-BODY INJECTOR OR PRE-FILLED SYRINGE AFTER CHEMOTHERAPY

Febrile neutropenia (FN) can be a serious complication of chemotherapy (CTX), but FN risk is reduced with pegfilgrastim, optimally administered the day after CTX. An on-body injector (OBI) supports optimal timing of pegfilgrastim receipt by eliminating a return visit for administration via pre-filled syringe (PFS). The aim was to compare CTX cycles including pegfilgrastim administered via OBI or PFS. CTX cycles including pegfilgrastim 1/1/2017-5/31/2018 were identified using healthcare claims in the IBM® MarketScan® Research Databases. FN incidence was measured in each cycle, up to six cycles. Driving time and distance were calculated from the centroid of the patient zip code to the provider address. Weather following CTX was captured using the IBM MarketScan Weather Database. Among 433,657 cycles, 36,421 included pegfilgrastim, and 73.9% were PFS. OBI was primarily on CTX end date (“timely”; 98.5%). PFS was on CTX end date (“early”; 58.4%), day after (“timely”; 27.3%), and 2-5 days after (“late”; 14.3%). FN incidence was lower among OBI vs. PFS cycles (1.4% vs. 1.7%, p=0.01). More early and late PFS cycles completed CTX before holidays/weekends vs. timely PFS (22.9% vs. 7.1%, p<0.001). Extreme heat and precipitation (>90th percentile) occurred more during late vs. timely PFS cycles (heat: 18.1% vs. 9.3%; precipitation: 24.9% vs. 10.7%; p<0.001). Driving distance and time were greater among early and late vs. timely PFS cycles (distance: 25.6, 24.0 vs. 22.1 miles; time: 34.4, 33.6 vs. 31.5 minutes; p<0.001). Timing of pegfilgrastim receipt was optimal for almost all OBI cycles, and suboptimal for most PFS cycles. CTX before holidays/weekends, adverse weather, and longer drive times may prevent patients from receiving pegfilgrastim the day after CTX. Use of OBI can possibly remove barriers to timely pegfilgrastim receipt and reduce incidence of FN among appropriate patients.

Abstract P2-12-02: Quality of life data of breast cancer patients receiving a fixed combination of netupitant/palonosetron (NEPA) for prevention of chemotherapy-induced nausea and vomiting - A real life study

Abstract Background: NEPA, an oral fixed dose combination of netupitant at 300 mg and palonosetron at 500 mg has been approved for the prevention of acute and delayed chemotherapy (Ctx)-induced nausea and vomiting (CINV) in cancer patients (pts) receiving highly (HEC) or moderately emetogenic chemotherapy (MEC). The primary objective of the prospective, non-interventional study (NIS) AkyPRO was the evaluation of quality of life (QoL) in adults receiving NEPA as primary prophylaxis for CINV associated with MEC or HEC. Secondary endpoints were efficacy and safety of NEPA. Here, we present an interim analysis in the subgroup of breast cancer (BC) pts, who represent the largest subpopulation (66%) enrolled in the AkyPRO. Since September 2015, 2427 pts have been recruited, of whom 986 suffered from BC. Methods: This NIS has been designed to evaluate NEPA in 2,500 cancer pts receiving single day or two day MEC or HEC. QoL was recorded by FLIE questionnaires. Efficacy of NEPA as indicated by complete response (CR: no vomiting, no rescue medication), additional medication, and adverse events were recorded in patient diaries over three consecutive Ctx cycles. Patients and physicians documented overall antiemetic efficacy on a 4-point scale (very good, good, satisfactory, poor). Results: At the cut-off date November 11, 2017, 2427 pts had been enrolled in the study. For the interim analysis, 986 BC pts were evaluated who had been completely documented in the eCRF at the cut-off date. 80% of pts received HEC, mostly (79%) anthracycline/cyclophosphamide (AC) combinations. Of the women receiving MEC, the majority were treated with carboplatin-based regimens (9%). 7% of patients received other MEC regimens. More than 84% of pts reported no impact on daily life due to vomiting in all analysed cycles. The percentage of pts with no impact on daily life due to nausea ranged from 51-56%. More than 93% of pts reported no emesis and more than 81% reported CR during the 5 days post-chemotherapy during all 3 cycles. Nausea was more difficult to control, 37% of pts documented to have suffered from nausea one or more times during the 5 days following chemotherapy. Effectiveness, evaluated by physicians’ assessment, was rated very good/good for 89 -91% of the pts in cycle 1, 2, and 3. Comparison of patients’ and physicians’ perception of antiemetic treatment effectiveness showed that patients judged the effectiveness equally well. NEPA was well tolerated. Low-grade constipation (2.2%) and insomnia (1.4%) were the most frequent treatment-related adverse events. Conclusion: In this real-life study, NEPA was effective in the prevention of CINV in the subgroup of breast cancer pts receiving HEC or MEC. Together with its convenient administration attributes of one single dose per ctx cycle, NEPA might facilitate adherence to antiemetic guidelines and ultimately may improve CINV control. Citation Format: Jörg Schilling, Steffi Busch, Andrea Stefek, Eberhard Müller, Jürgen Schwickerath, Falk Altmann, Martin Holländer, Meinolf Karthaus. Quality of life data of breast cancer patients receiving a fixed combination of netupitant/palonosetron (NEPA) for prevention of chemotherapy-induced nausea and vomiting - A real life study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-02.

2392. Identifying Associations Between Clostridium difficile Infection Incidence and Cancer Patients Receiving Chemotherapy

Background Clostridium difficile infection (CDI) is a known major financial burden. In the cancer population, CDI, was identified to have a peak incidence of 17.2 per 1000 patients with increased morbidity, mortality and hospital length of stay. The need to further elucidate chemotherapy (CTX) with vs. without ABX usage as risk factors among other variables in cancer patients arises since this population is already baseline immunocompromised.MethodsA retrospective case–control study (total of 1989 cancer patients who received CTX and had diarrhea at UTMB through 1/2016–1/2018) was completed. Subjects were screened using extensive inclusion and exclusion criteria, and assigned as CASES (with symptomatic (s) diarrhea from proven CDI) and as CONTROLS (had diarrhea but not attributed to CDI). A 1:1 subject matching using age, sex and past medical histories was completed and a total of 46 patients: 23 cases and 23 controls were compared and analyzed. McNemar’s and independent t test of equal variance were used for association and comparing means/medians, respectively. Two-sided P value ≤ 0.05 was considered significant.ResultsThe use of ABX (OR = 16, P = 0.0007) and having any degree of neutropenia at the time of diarrhea (OR = 12, P = 0.0055) among CTX patients had significant associations with having sCDI. Although no significant association between sCDI and # of days post CTX exposure (≥7 days (P = 0.1138) and ≥14 days post CTX (P = 0.1489) was identified, a mean of 12.83 ± 7.69 days passed before sCDI diagnosis in cases, compared with diarrhea diagnosis (7.46 ± 6.1 days) in controls (P = 0.0119). Meanwhile, receiving >1 CTX cycle (P = 1.000) and particular CTX types (P = ~ 0.0771–1.000) had no significant associations with sCDI diagnosis.ConclusionAny ABX usage post CTX exposure heavily predisposes to sCDI among cancer patients likely due to elimination of gut flora on an already predisposed population. Having any degree of neutropenia was also associated with having sCDI likely due to significant immunosuppression on top of being baseline cancer patients receiving CTX, and may have predictability benefits. The other variables may have not been significant due to expected limited cases because of low CDI incidence. Disclosures All authors: No reported disclosures.

1816P - Prophylaxis with lipegfilgrastim in patients with primary breast cancer receiving dose dense chemotherapy: Results from the German NIS NADENS

BackgroundOnly limited data are available on the impact of primary prophylactic use of G-CSF in high risk breast cancer (BC) patients (pts) treated with dose dense (dd) chemotherapy (CTx) protocols in standard clinical practice. Lipegfilgrastim (LF) is a glyco-pegylated long-acting G-CSF indicated to reduce the duration of neutropenia and the incidence of febrile neutropenia (FN). MethodsNADENS was a multi-center, prospective, non-interventional study (NIS) in Germany on the primary prophylactic LF administration for BC pts treated with dd two-weekly CTx. 328 pts were enrolled at 68 sites (27 hospitals with 143 pts, 41 private practices with 185 pts, Safety Set (SAF)). Due to protocol violations 46 pts were excluded from analysis set (282 pts). ResultsSevere neutropenia (SN, grade 3/4) occurred in 131 pts (46.5%) at least once during max. 4 observed cycles. Incidences in cycles 1/2/3/4 were 33.3%/22.1%/22.9%/19.8%, respectively. 6 pts (2.1%) experienced a FN, (incidence per cycle 1.1%/0.4%/1.4%/0.4%). Altogether 275 SN and 9 FN events were documented for the 1,121 observed CTx cycles. CTx had to be modified in 74 pts (26.2%). 96 pts (34.0%) received anti-infectives. 35 pts were hospitalized (12.4%) with 51 single hospitalizations. Reasons included FN (4 events), other neutropenic complications (5) and infections (7). No stay on ICU was reported. AEs were observed for 119 pts (36.3% of SAF, 342 events) and SAEs for 23 pts (7.0%, 30 events). No AE was fatal, 12 AEs (3.6%) were rated as grade 4. 89 AEs (in 61 pts) were classified as probable or possible drug related. For 280 pts (99.3%) treatment with LF was rated as ‘beneficial’ by the treating physician. Tolerability of LF treatment was assessed mostly as ’very good’ (152 pts, 53.9%) or ’good’ (120 pts, 42.6%), ’moderate’ was documented for 8 pts (2.8%), ’bad’ for 2 pts (0.7%). ConclusionsNADENS provides a realistic picture about the use and efficacy of LF for this defined patient group in daily clinical care in Germany. LF was found to be effective and safe and results fall in the range of those observed in RCTs. No new safety signal was detected. The known limitations of non-interventional studies have to be considered. Clinical trial identificationXM22-ONC-40115 (BfArM NIS No 7038). Legal entity responsible for the studyTeva GmbH, Ulm, Germany. FundingTeva GmbH, Ulm, Germany. DisclosureM. Kiechle: Advisory / Consultancy: Teva GmbH. C. Schem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Teva GmbH. D. Lüftner: Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Teva GmbH; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Amgen; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: AstraZeneca; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Celgene; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Lilly; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Loreal; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: MSD; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Mundipharma; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Mylan; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Novartis; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Pfizer; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Roche; Non-remunerated activity/ies, Honoraria for Advisory Board activities and/or oral presentations: Tesaro. X. Hamann: Full / Part-time employment: Teva GmbH. R. Jünemann: Full / Part-time employment: Teva GmbH. M. Tölg: Honoraria (institution), CRO for reported study: Teva GmbH. U. Köhler: Advisory / Consultancy: Teva GmbH.

Development and evaluation of the Cancer Symptom Management System: Symptom Management Improves your LifE (SMILE)-a randomized controlled trial.

To develop a Cancer Symptom Management System: Symptom Management Improves your LifE (SMILE) and evaluate the effect and feasibility of the system in cancer symptom management. The Cancer Symptom Management System: SMILE was developed, and a nonblinded, randomized controlled trial was conducted. Cancer patients starting adjuvant or palliative chemotherapy (CTx) were enrolled and randomized to control (symptom monitoring), experimental 1 (Exp 1; symptom monitoring + report), or experimental 2 (Exp 2; symptom monitoring + report + Oncology Nursing Society putting evidence into practice (ONS PEP)-guided evidence-based symptom management education) groups in a 1:2:2 ratio (N = 249). To evaluate whether symptom management education provided additional benefit to continuous symptom monitoring, the Exp 1 and Exp 2 groups were compared utilizing Mann-Whitney U test and generalized estimating equations (n = 199). Symptom severity (symptom total score) at each measurement point was not different among the three groups (p > .05). Fatigue and sleep disturbance changes were different between Exp 1 and Exp 2 among patients receiving adjuvant CTx (p = .042 and p = .008). Fatigue gradually decreased after a peak at the 1st CTx cycle in Exp 2, whereas Exp 1 experienced increasing fatigue until the 3rd CTx cycle. A gradual decrease in sleep disturbance was observed in Exp 2 after the 2nd CTx cycle, whereas Exp 1 experienced a steady increase in the symptom. Participants were willing to participate in symptom monitoring using the cancer symptom management system. Symptom management education was easy to follow and helpful. The application of the Cancer Symptom Management System: SMILE incorporating ONS PEP-guided evidence-based symptom management education effectively managed fatigue and sleep disturbance after adjuvant CTx. The feasibility of the system has been demonstrated. Incorporating the system into electronic medical systems and integrating provider input will be necessary.

Investigation of the efficacy of imidazolyl ethanamide pentandioic acid (IEPA) to reduce chemotherapy-induced myelosuppression (CIM) in breast cancer patients.

e23098 Background: Neutropenia is a major toxicity of myelosuppressive chemotherapy (CTX). Treatment and prophylaxis of CTX-induced neutropenia with granulocyte colony-stimulating factors is mainly recommended in patients with high risk of febrile neutropenia. IEPA, a hemoprotective small molecule for oral use, may constitute a safe alternative. The main objective of the study was to assess the efficacy of IEPA in reducing CIM in breast cancer patients. Methods: Randomized, double-blind, placebo-controlled, parallel group study in female adults diagnosed with invasive breast cancer receiving epirubicin/cyclophosphamide CTX. Patients took one tablet daily of IEPA 100 mg or placebo starting 5 days prior to the first CTX cycle until 3 days prior to the second CTX cycle. Two batches of study medication were used sequentially in the study. Hematologic and other variables were tightly measured during the first CTX cycle. Results: After no significant treatment effect was observed in the total study results, post-hoc analyses revealed a significant batch effect. Treatment with Batch 1 IEPA was superior to placebo in treating CIM (Table). Conclusions: Although the presence of a batch effect precludes final conclusions and calls for a formulation optimization of the compound, the efficacy of Batch 1 IEPA in reducing CIM consistent with prior non-clinical and clinical studies invites further investigation of the hemoprotective properties of IEPA. Area over the curve (AOC) integrates extent and duration of decreased absolute neutrophil counts [(ANC/nL)*days] below thresholds corresponding to grade 1 (ANC &lt; 2.0x10^9/L) and 3 neutropenia (ANC &lt; 1.0x10^9/L); CI: confidence interval; LS: least squares; DN3: duration of grade 3 neutropenia in [days]. Clinical trial information: NCT02692742. [Table: see text]

Induced Myelosuppression and Recommendation for Monitoring of Absolute Neutrophil Counts in Patients Treated with Epirubicin and Cyclophosphamide in Early Breast Cancer: Results from a Phase 2a Collaborative Trial of the AGO-B and CESAR Study Groups

IntroductionDespite much progress in the treatment of patients with malignant disorders, severe neutropenia and infections are frequent adverse events associated with standard chemotherapy regimens.Due to the low frequency of neutrophil monitoring in most clinical studies, limited insights exist about the time of the nadir, the lowest absolute neutrophil counts (ANCs), and the adequate timing of complete blood counts (CBCs) in clinical practice.ObjectiveTo analyze the trajectory of ANCs in a patient population undergoing anthracycline and cyclophosphamide treatment with the aim of producing a recommendation for the optimal time to monitor the ANCs.MethodsThe MyeloConcept Study is a randomized, double-blind, placebo-controlled, multi-centre phase 2a study, in which patients received adjuvant or neoadjuvant chemotherapy for the treatment of breast cancer. Patients were either randomized into a placebo group or an imidazolyl ethanamide pentandioic acid (IEPA, Myelo001) treatment group. The study was conducted at 23 sites in Germany between March 2016 and November 2017 (NCT02692742).This abstract reports on the placebo group of 65 patients who received background treatment with epirubicin (E) 90 mg/m2 BSA (body surface area) + cyclophosphamide (C) 600 mg/m2 BSA q21d. Patients' CBCs were measured in a central and/or local laboratory at least 9 times (on average every three days), throughout the first chemotherapy (CTX) cycle with an increased frequency when ANC decreased < 1.0 × 109 cells/L. Linear interpolation was used to obtain a continuous ANC time curve. The first occurrence and presence of grade 4 neutropenia among subjects who developed a grade 4 neutropenia were assessed on each possible monitoring day. The participating study sites provided data in the form of a questionnaire to assess ‘real-life’ ANC monitoring practice.ResultsThe mean age of the 65 female breast cancer patients was 55.7 years (SD 10.66; median 57.0), ECOG was grade 0 in > 95% of patients (Table 1). The mean time after CTX start to the ANC nadir was 13.8 days (SD 1.31; median 14.0). ANC CTCAE severity grades 3 and 4 were reached in 65 (100%) and 53 (81.5%) subjects, respectively, in the first CTX cycle (Table 2). The mean duration of grade 3 and 4 neutropenia was 7.81 days (SD 2.46; median 7.77) and 5.57 days (SD 2.48; median 5.44), respectively.Among subjects who developed a grade 4 neutropenia in this study population, the onset of grade 4 neutropenia occurred between day 10 and day 15, and most prominently on days 11 and 12 (32% and 25% of subjects, respectively (Table 3)). The greatest presence of grade 4 neutropenia (i.e. new onset or already existent neutropenia) occurred on days 13, 14 and 15 (79, 85 and 89% respectively).Based on a questionnaire of the real-life practices of the 23 participating sites, 83% (1 site gave no answer (n.a.)) evaluated CBCs at the beginning of the first cycle of CTX and during the cycle once (26%), twice (48%) or three times (9%), whereas 17% of sites did not monitor CBCs. Blood counts were assessed most frequently on days 7, 8 or 15 and monitoring was commonly (65%, 2 sites n.a.) increased once the neutrophil count fell below a certain ANC threshold, mainly below 0.5 × 109 cells/L.ConclusionsWith all subjects experiencing neutropenia grade ≥ 3 during the first CTX cycle, severe ANC toxicities undergoing q21d anthracycline and cyclophosphamide (EC) treatment were more frequently observed in this study than previously reported (Smith et al., 2006). This finding may be due to the considerably higher frequency ANC monitoring compared to prior clinical studies.In contrast to the existing ‘real-life’ practice reported, in-cycle ANC monitoring may be most informative if measured on day 11 or day 12 to assess the first occurrence (incidence) and on days 13 to 15 for the presence of grade 4 neutropenia (prevalence). A reliable and early detection system for grade 4 neutropenia offers an opportunity for the instigation of preventative measures to mitigate the infection risk for patients. DisclosuresPleimes:Bayer: Consultancy, Equity Ownership; Myelo Therapeutics: Employment, Equity Ownership. Möbus:Teva: Consultancy; Roche: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Myelo Therapeutics: Other: Chair of the Steering Committee of the MyeloConcept Study. Mayer:MSD: Speakers Bureau; Lily: Other: Medical Advisory Board; Myelo Therapeutics: Other: Member of the Steering Committee and Principle Investigator of MyeloConcept Study; BMS: Speakers Bureau; Incyte: Speakers Bureau. Schmidt:Janssen: Honoraria; Sividon: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Pierre-Fabre: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Myriad Genetics: Consultancy, Honoraria; Myelo Therapeutics: Other: Member of the Steering Committee of MyeloConcept Study; Eisai: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria. Asang:Myelo Therapeutics GmbH: Employment. Flunkert:Myelo Therapeutics GmbH: Consultancy, Other: Kathrin Flunkert is a salaried employee of M.A.R.C.O. GmbH & Co. KG. M.A.R.C.O. GmbH & Co. KG. had a master service agreement and received payments by Myelo Therapeutics GmbH to conduct the statistical analysis for Myelo Therapeutics. . Mikus:Myelo Therapeutics: Consultancy, Other: Member of the Data Safety Monitoring Board.