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Lenograstim

Cancer patients treated with chemotherapy and who are prescribed commercially available filgrastim biosimilar for primary or secondary prophylaxis for FN.

Sandoz GmBH

This international, prospective, observational, open-label, pharmaco-epidemiologic study observes cancer patients at risk for chemotherapy-induced febrile neutropenia (FN) who are receiving filgrastim biosimilar (EP2006) for primary or secondary FN prophylaxis to better describe the patient population at risk for FN and treated prophylactically in physician's best clinical judgement with filgrastim biosimilar (EP2006), to describe prophylaxis patterns involving filgrastim biosimilar (EP2006), and to evaluate hematology levels and variability in hematological outcomes, impact on chemotherapy delivery, radiotherapy, surgery, and mortality. Additionally the study aims to identify patient cohorts who are vulnerable to poor response to FN prophylaxis and experience break-through episodes of FN, understand the differences between prophylaxis responders and non-responders, and describe the degree to which prophylaxis of FN is in congruence with guideline recommendations.

Multi-level Evaluation of Chemotherapy-induced Febrile Neutropenia Prophylaxis, Outcomes, and Determinants With Granulocyte-colony Stimulating Factor

International, Prospective, Open-label, Multicenter, Pharmacoepidemiological Study to Determine Predictors of Clinical Outcomes in Chemotherapy-treated Cancer Patients at Risk for Febrile Neutropenia and Treated Prophylactically With Filgrastim Biosimilar.

Objective 1: To describe the cancer patients requiring chemotherapy who, in their treating physician's best clinical judgment, are receiving EP2006 for the primary or secondary prophylaxis of FN in terms of demographics, clinical status, medical history, concomitant comorbid conditions and current status of disease, and prior and concomitant medications.

Chemotherapy regimens were classified for FN risk (\<10% risk, 10-20% risk or \>20% risk) according to the published rates in the EORTC Guidelines under consideration of agent(s) and schedules.

ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia;

Objective 1: To describe the cancer patients requiring chemotherapy who, in their treating physician's best clinical judgment, are receiving EP2006 for the primary or secondary prophylaxis of FN in terms of demographics, clinical status, medical history, concomitant comorbid conditions and current status of disease, and prior and concomitant medications.

ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia;

Objective 1: To describe the cancer patients requiring chemotherapy who, in their treating physician's best clinical judgment, are receiving EP2006 for the primary or secondary prophylaxis of FN in terms of demographics, clinical status, medical history, concomitant comorbid conditions and current status of disease, and prior and concomitant medications.

ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia

Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

\* Advanced disease is defined as Stage IV (Stage III or IV if multiple myeloma) AND prior chemotherapy in metastatic setting. The PRS is a quantification of eight individual patient risk factors (EORTC guidelines-2010).

CV: cardiovascular; EORTC: European Organization for Research and Treatment in Cancer; FN: febrile neutropenia; Hb: hemoglobin

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

\* Advanced disease is defined as Stage IV (Stage III or IV if multiple myeloma) AND prior chemotherapy in metastatic setting CV: cardiovascular; EORTC: European Organization for Research and Treatment in Cancer; FN: febrile neutropenia; Hb: hemoglobin

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

Patient risk score (PRS) shows the individual patient risk for FN.The PRS is a sum of eight weighted individual patient risk factors for FN and results in a possible score of 0 to 11 (highest risk for FN). The risk factors were assigned weights based on the level of risk specified by guidelines and SC consensus (age \> 65 years: 3.0; advanced disease: 1.5; history of FN: 3.0; No antibiotic prophylaxis: 0.5; poor performance/nutritional status: 1.5; female gender: 0.5; Hb\<12g/dL: 0.5; Renal, CV or liver disease: 0.5).

Advanced disease: Stage IV or Stage III + prior chemotherapy in metastatic setting; CV: cardiovascular; EORTC: European Organization for Research and Treatment in Cancer; FN: febrile neutropenia

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

FN: Febrile Neutropenia; EORTC: European Organisation for Research and Treatment of Cancer

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

The CRS quantifies whether the decision to initiate EP2006 as either primary or secondary prophylaxis is consistent with the EORTC guideline (2010) recommendation based upon the patient's chemotherapy toxicity (\<10%, 10-20% or \>20% risk of FN) and the PRS. There are three possible results: under-treated, correctly treated, over-treated

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

\^ 168 cycles in which ZARZIO® was initiated on day 4 or later involved regimens deemed by the Study Steering Committee to be suitable for GCSF initiation any day after chemotherapy (day 1 or later), e.g., etoposide; hence, these patients were re-classified as being within guidelines

DLBCL- Diffuse Large B-Cell Lymphoma. Guidelines refers to EORTC 2010 guidelines

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

ANC=Absolute Neutrophil Count; GIS Score 0 (EP2006 initiated on day 0 of chemotherapy or on day 10 or later); GIS Score 0.50 (EP2006 initiated on days 7-9 of chemotherapy); GIS Score 0.75 (EP2006 initiated on days 4-6 of chemotherapy); GIS Score 1.00 (EP2006 initiated per EORTC guidelines (2010) on days 1-3 after chemotherapy)

ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; EORTC=European Organization for Research and Treatment in Cancer; FN=Febrile Neutropenia; GCSF=Granulocyte Colony-Stimulating Factor; GIS=Granulocyte Colony-Stimulating Factor Initiation Score

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

The GPS grades persistence based on the number of cycles in the line of chemotherapy in which EP2006 was administered, D, relative to the number of cycles in which it should have been continued, C. Thus, the GPS = D/C and ranges from 0 to 1.0

ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; EORTC=European Organization for Research and Treatment in Cancer; FN=Febrile Neutropenia; GCSF=Granulocyte Colony-Stimulating Factor

Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

The GCS is computed at the patient level as an overall grade of how congruent actual GCSF treatment is to recommended treatment. The GCS is computed as follows and scores range from 0 to 3: GCS = Σ(CRS + mean GIS over all cycles + GPS), with higher scores indicating higher congruence.

CRS: Chemotherapy Risk Score (0 or 1 with 1 best); FN: febrile neutropenia; GCSF: granulocyte colony-stimulating factor; GIS=GCSF Initiation Score (0 to 1 with 1 best); GPS=GCSF persistence score (0 to 1 with 1 best);

Objective 4: To describe hematological outcomes observed in association with primary and secondary prophylactic use of EP2006 in patients at risk for FN; including break-through episodes of FN.

Objective 4: To describe hematological outcomes observed in association with primary and secondary prophylactic use of EP2006 in patients at risk for FN; including break-through episodes of FN.

CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; Chemotherapy disturbance=dose reduction, delay, and/or cancellation; Composite (any of CIN grade 4, FN, CIN/FN-related hospitalization or CIN/FN-related chemotherapy disturbance)

A patient may fall into more than one or none of the categories displayed.

Objective 4: To describe hematological outcomes observed in association with primary and secondary prophylactic use of EP2006 in patients at risk for FN; including break-through episodes of FN.

Chemotherapy-Induced Neutropenia (CIN); Febrile Neutropenia (FN); Chemotherapy disturbance=dose reduction, delay, and/or cancellation; Composite (any of CIN grade 4, FN, CIN/FN-related hospitalization \[RH\] or CIN/FN-related chemotherapy disturbance \[RCD\])

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents incidences of different outcomes and composite outcome by chemotherapy risk group. \^Composite endpoint includes any of CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance.

CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents incidences of different outcomes and composite outcome by prophylaxis decision (relative to guidelines). \^Composite endpoint includes any of CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance.

CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents incidences of outcomes by day (mean GIS over all visits). \^Composite outcome includes CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance

CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents incidences of outcomes on a cycle level. \^Composite outcome includes CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance

CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents incidences of outcomes on a cycle level by day of study drug initiation. \^Composite outcome includes CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance

CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010). \*Day of EP2006 initiation- Day 0 (during chemotherapy); \*\*Day of EP2006 initiation- Days 1-3 (per guidelines)

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents incidences of outcomes on a cycle level by study drug duration. \^Composite outcome includes CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance

CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia;

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table shows number of patients that died in each group.

CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table shows number of patients who died by any or no CIN/FN related chemotherapy disturbance.

CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents number of patients that had a cancer-related death by any/no grade 4 CIN or FN

CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents number of patients who had a cancer-related death by any/no CIN/FN-related chemotherapy disturbance

CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents number of patients with any CIN/FN-related chemotherapy disturbance by prophylaxis type.

CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia

Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

Table presents number of patients with any CIN/FN-related chemotherapy disturbances by treatment decision.

CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia

Objective 6: To examine the multilevel determinants (patient, center) of hematological outcomes of primary and secondary prophylaxis with EP2006 to better understand the variability in outcomes achieved.

Hierarchical modeling was used to test the relationship of patient- and physician/center-level variables and treatment response in terms of ANC. This analysis was conducted at the cycle level using a 1-cycle lag between treatment patterns and outcomes, that is study drug treatment patterns in one cycle predicted the ANC value at the beginning of the next cycle. Log-transformed ANC values were used.

Table presents predictors for ANC: GCSF decision, study drug dose, tumor type, patient gender, ECOG, Hb

Since log-transformed Absolute Neutrophil Count (ANC) values were used, Exp(beta) can be interpreted in terms of % change in ANC for each unit change in predictor or for each category relative to the referent (for categorical variables); Hb=Hemoglobin

Objective 6: To examine the multilevel determinants (patient, center) of hematological outcomes of primary and secondary prophylaxis with EP2006 to better understand the variability in outcomes achieved.

Mean and standard error estimated from ANCOVA

Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

Table presents number of cycles by day after chemotherapy.

Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery

Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

A two-group solution converged and the groups differentiated on key baseline variables. However, the group sizes were too unevenly distributed for further analysis with the "high risk group" comprised of only 3.0% of the evaluable sample.

ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia

Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

ECOG score is a severity scale from 0 to 5 (highest) to grade toxicity and is defined as follows: 0=none, 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=lethal. ECOG is described in more detail by Oken et al, Am J Clin Oncol (CCT) 5:649-655, 1982.

FN=Febrile Neutropenia; ECOG: European Cooperative Oncology Group

Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

FN=Febrile Neutropenia

Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

CIN=Chemotherapy Induced Neutropenia; FN=Febrile Neutropenia

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006

Only results with a p-value of \<0.05 are added as statistical analyses appendices.

CI: confidence interval; CIN: chemotherapy-induced neutropenia; GCSF: granulocyte colony-stimulating factor; GIS: GCSF Initiation Score

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006

Only results with a p-value of \<0.05 are shown in the statistical appendices.

H/o=History of; CI=confidence interval; CIN=chemotherapy-induced neutropenia

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

Only results with a p-value of \<0.05 are shown in the statistical appendices.

CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia; ECOG: Eastern Cooperative Oncology Group

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006

Only results with a p-value of \<0.05 are shown in the statistical appendices.

CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

Only results with a p-value of \<0.05 are shown in the statistical appendices.

CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia; ECOG: Eastern Cooperative Oncology Group.

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

Only results with a p-value of \<0.05 are shown in the statistical appendices.

CI: confidence interval; CIN: chemotherapy-induced neutropenia; GCSF: granulocyte colony-stimulating factor; GIS: GCSF Initiation Score; Chemotherapy disturbance=dose reduction, delay, and/or cancellation

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

Only results with a p-value of \<0.05 are shown in the statistical appendices.

CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

Only results with a p-value of \<0.05 are shown in the statistical appendices.

CI: confidence interval; CIN: chemotherapy-induced neutropenia; ECOG: Eastern Cooperative Oncology Group; FN: febrile neutropenia; GCSF: granulocyte colony-stimulating factor; GIS: GCSF Initiation Score.

Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

Only results with a p-value of \<0.05 are shown in the statistical appendices.

CI: confidence interval; CIN: chemotherapy-induced neutropenia; ECOG: Eastern Cooperative Oncology Group; FN: febrile neutropenia; GCSF: granulocyte colony-stimulating factor; GIS: GCSF Initiation Score. H/o repeated infections refers at enrollment; H/o: History of

Objective 10: To model patient- and center-level variables between patients who died vs. survived during the course of primary or secondary prophylaxis with EP2006, in all patients and those with break-through FN episodes.

Table presents patient-level predictors for all-cause mortality: history of anemia at enrollment, liver/renal/cardiac comorbidity, poor performance (ECOG \>=2) during study

Objective 10: To model patient- and center-level variables between patients who died vs. survived during the course of primary or secondary prophylaxis with EP2006 in all patients and those with break-through FN episodes.

Table presents patient level predictors for cancer-related mortality: female gender, poor performance (ECOG \>=2) during study.

ECOG score is a severity scale from 0 to 5 (highest) to grade toxicity and is defined as follows: 0=none, 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=lethal. ECOG is described in more detail by Oken et al, Am J Clin Oncol (CCT) 5:649-655, 1982.

Sandoz

The occurrence of adverse drug reactions (ADRs) not including not-related (S)AEs was sought by non-directive questioning of the patient at each visit during the study. Only Adverse events with a suspected relationship to EP2006 were collected.

Cancer patients treated with chemotherapy and who are prescribed commercially available filgrastim biosimilar for primary or secondary prophylaxis for FN. Number 1496 refers to the total number of patients who received at least one dose of study medication EP2006.

EP2006

Cancer patients treated with chemotherapy and who are prescribed commercially available filgrastim biosimilar for primary or secondary prophylaxis for FN. Only patients who had no major protocol violations and have a minimum of enrollment cycle and either one follow-up cycle or study end data with valid outcome data (i.e., ANC or completed CIN/FN data) belong to the evaluable sample and are analyzed.

EP2006, Evaluable Sample

Age, Continuous

Sex: Female, Male

Caucasian

African

Asian

Other

Missing

Race/Ethnicity, Customized

France

Hungary

Czech Republic

Spain

Poland

Belgium

Romania

Austria

Germany

United Kingdom

Switzerland

Italy

Region of Enrollment

Height

Weight

Body-Mass Index (BMI)

Bone pain

Joint pain

Muscle pain

Headache

Epistaxis

GI bleeding

Skin hemorrhage

Medical history for each patient was recorded. A patient can fall into more than one or none of the categories displayed.

Medical history

Hypertension

Anemia

Diabetes Type II

Coronary disease

Allergies

COPD

Comorbidities for each patient were recorded. Only those comorbidities with a relative frequency of 5% or more are displayed in the table. A patient can fall into more than one or none of the categories displayed.

Comorbidities

History of any repeated infection

Type of repeated infection (chronic)

Type of repeated infection (recurrent, acute)

1 infectious episode in past 3 months

2 infectious episodes in past 3 months

3 or more infectious episodes in past 3 months

History of repeated infections for each patient was recoded. A patient can fall into more than one or none of the categories displayed.

History of repeated infections

Breast

Lung

Lymphoma (DLBCL)

Ovarian

Prostate

Multiple myeloma

Bladder

Cancer type

Breast (stage III, n=466)

Breast (stage IV, n=466)

Lung (stage III, n=345)

Lung (stage IV, n=345)

Lymphoma (DLBCL) (stage III, n=245)

Lymphoma (DLBCL) (stage IV, n=245)

Ovarian (stage III, n=140)

Ovarian (stage IV, n=140)

Prostate (stage III, n=102)

Prostate (stage IV, n=102)

Multiple myeloma (stage III, n=85)

Multiple myeloma (stage IV, n=85)

Bladder (stage III, n=64)

Bladder (stage IV, n=64)

Overall, Stage III

Overall, Stage IV

Breast (unknown, n=466)

Lung (unknown, n=345)

Lymphoma (DLBCL) (unknown, n=245)

Multiple myeloma (unknown, N=85)

Overall, unknown

Table presents cancer stage by cancer stage. In addition, table presents cancer stage for all patients.

Cancer stage & type

None

Surgery

Chemotherapy

Radiation therapy

Hormonal therapy

Targeted therapy

Bone marrow transplant

Prior cancer treatments for all patients are recorded. A patient can have more than one prior cancer treatment. In addition, prior chemotherapy is also displayed by adjuvant or metastatic setting for those patients for whom this information was available.

Prior cancer treatments

Baseline characteristics are based on the evaluable sample, e.g. all patients who received at least one dose of the study medication, had no major protocol violation and have a minimum of enrollment cycle and either one follow-up cycle or study end data with valid outcome data (i.e., ANC or completed CIN/FN data).

Spots Global Cancer Trial Database for primary prophylaxis