Prophylaxis of chemotherapy-induced febrile neutropenia with biosimilar fi lgrastim: Description of patients, treatment patterns and

outcomes in the MONITOR-GCSF Study in RomaniaL. Miron1, M. Marinca1, I. Miron2, E. Prisacariu3

1Regional Oncology Institute Iasi, Romania , 2„Sf. Maria” Hospital Iasi, Romania, 3Sandoz Pharma Services, Romania

Introduction• Chemotherapy-induced febrile neutropenia (CIN/FN) is

a frequent and potentially life-threatening complication experienced in patients undergoing cancer treatment. FN can result in hospitalization and can jeopardize antineoplastic treatment through chemotherapy delay or dose reduction1,2 as well as delays and cancellations of surgery. FN is also associated with increased morbidity, mortality, and health care costs.3

• The European Organization for Research and Treatment of Cancer (EORTC), among other clinical organizations, has established evidence-based guidelines for the use of granulocyte colony-stimulating factor (G-CSF) to reduce the incidence of CIN/FN.4

• The primary aims of the MONITOR-GCSF study are to5:

– describe the patient population at risk for FN and treated prophylactically with biosimilar fi lgrastim (Zarzio®, Sandoz)

– describe prophylaxis patterns involving Zarzio® and their congruence with the EORTC guidelines

– identify the multi-level (patient- and centre-level) determinants of patient outcomes in terms of breakthrough episodes of CIN/FN and impact on chemotherapy delivery.

• This current analysis describes the patient characteristics, treatment patterns of Zarzio®, and outcomes in the Romanian sample.

Methods• MONITOR-GCSF is an international, prospective, observational,

open-label, pharmaco-epidemiologic study of cancer patients at risk of CIN/FN who received commercially available Zarzio® for prophylactic purposes.

• Treatment with Zarzio® was per the treating physician’s best clinical judgment. Thus, there was no fi xed protocol for treatment initiation, dose, or duration; data were collected on the actual real-world practice patterns for up to six chemotherapy cycles.

• Treatment with Zarzio® is described relative to the EORTC guideline recommendations.4 The EORTC guideline algorithm is illustrated in Figure 1.

• 64 evaluable patients from 7 centers in Romania (from a total of 1447 patients from 140 centers from 12 European countries) participating in the MONITOR-GCSF study are presented in these analyses which include 300 cycles.

Results• Table 1 lists patient demographic characteristics and Figure 2

presents cancer types. The most common cancers were diffuse large B-cell lymphoma (DLBCL) (33%), breast (23%), and multiple myeloma (19%) with a majority of patients (51.6%) having hematological cancers and 48.4% with solid tumors.

• Figure 3 shows chemotherapy-related risk of FN for all patients and for patients with hematological cancer (hematology) and solid tumors (oncology). A higher percentage of hematology patients (55%) were treated with chemotherapy regimens that have high risk (>20%) of associated FN compared with oncology patients (35%).

• Figure 4 illustrates patient-related risk factors for FN for all patients and for those treated with chemotherapy regimens with medium risk (10–20%) of associated FN.

• Zarzio® prophylaxis initiation (primary vs. secondary) relative to the EORTC guideline recommendations is illustrated in Figure 5. Primary prophylaxis was initiated in 69% of all patients, with 71% of hematology patients and 67% of oncology patients receiving primary prophylaxis. Prophylaxis, either primary or secondary, was correctly initiated per EORTC guideline recommendations (considering CIN/FN risk and patient-related factors) in 34% of patients.

• Table 2 presents Zarzio® treatment patterns. Zarzio® dose of 48 MIU/day was given in the majority (52.2%) of cycles and 30 MIU/day given in 47.8% of cycles. Zarzio® was started on average 1.0 ± 1.9 days after chemotherapy and given for 2.0 ± 1.0 days.

• CIN (any grade) occurred in 2.7% of all cycles and 9.4% of patients had one or more episodes of CIN (any grade); see Table 3. 6.3% of patients had at least one episode of Grade 3 or 4 CIN of which 1.6% were febrile. CIN/FN-related hospitalizations were experienced by 1.6% of patients. CIN/FN-related chemotherapy disturbances (dose reduction, delay or cancellation) occurred in 4.7%.

Conclusions• Real-world variations in practice patterns of

biosimilar G-CSF (Zarzio®) are evident in the Romanian sample in terms of:

– type of prophylaxis– prophylaxis decision (relative to guideline

recommendations)– day of initiation.

• Clinician decision to ‘over treat’ in the low and moderate chemotherapy risk groups may be due to patient-related risk factors, safety profi le of Zarzio®, and/or affordability of biosimilar G-CSF.

• Incidence of FN and CIN/FN-related hospitalizations is low.

• Zarzio® has similar real-world effectiveness as the originator and the G-CSF class in general.

References1. Lalami Y, et al. Support Care Cancer 2004;12:725–30.

2. Lyman GH, et al. Oncologist 2005;10:427–37.

3. Kuderer N, et al. J Clin Oncol 2007;25:3158–67.

4. Aapro MS, et al. Eur J Cancer 2011;47:8–32.

5. Gascón P, et al. Crit Rev Oncol Hematol 2011;77:184–97.

Figure 2. Cancer type

0 20 40 60 80 100

No concomitant antibiotic

Female

Hb <12 g/dL

Age >65

Renal, CV or liver disease

Poor performance/nutrition

Advanced disease

History of FN

All patients

Patients withchemotherapy risk 10–20%

Figure 4. Patient-related risks of FN per EORTC guidelines

Wszyscy pacjenci

48%

Pacjenci hematologiczni Pacjenci onkologiczni

71% 44%48%

44,9%

26% 48%

7,1%

3% 8%

Hematology patients

All patients

Oncology patients

bajo(<10%)medio (10-20%)alto (>20%)

Low (<10%)

Medium (10–20%)

High (≥20%)

All Patients

Figure 3. Chemotherapy-related risk for FN

CIN (any grade) occurred in 2.7% of all cycles and 9.4% of patients

PP SP

PP

PP

SP PP SP

PP SP

<10%17.2%

≥20%45.3%

C31.2%

U14.1% 3.1%

U1.6%

O21.9%

%

0%O

10.9%O

12.5% 0%O

4.7%

10–20%37.5%

Yes

CIN/FNin prior

cycle

No CIN/FNin priorcycle*

CIN/FNin prior

cycle

No CIN/FNin priorcycle*

No

FN risk

Chemotherapy toxicity

(% FN risk)

G-CSFdecision

Primary prophylaxis

SP Secondary prophylaxis

Distribution of the MONITOR-GCSF Romanian sample.

*Secondary prophylaxis started in cycle 2 or later despite no CIN/FN in prior cycle

Patient-related factors that increase overall risk of FN to >20%

CorrectG-CSF

decisionU = under

C = correct

O = over

C C C

Figure 5. Zarzio® initiation relative to the EORTC guidelines

STEP 1Assess frequency of FN associated

with the planned chemotherapy regimen

Prophylactic G-CSF recommended

FN risk ≥20% FN risk <10%FN risk 10–20%

Overall FN risk ≥20%

Overall FN risk<20%

STEP 2Assess factors that increase the frequency/risk of FN

STEP 3 Define the patient’s overall FN risk for planned

chemotherapy regimen

G-CSF prophylaxis not indicated

High risk Age >65 years

Increased risk(level I and II evidence)

Advanced diseaseHistory of prior FNNo antibiotic prophylaxis,no G-CSF use

Other factors(level III and IV evidence)

Poor performance and/or nutritional statusFemale genderHemoglobin <12 g/dLLiver, renal, or cardiovascular disease

Reassessat each

cycle

Figure 1. 2010 updated EORTC guideline algorithm

Table 1. Patient characteristics

GenderMale Female

39.1 % 60.9%

Age (years) Mean ± SD (min, max) 58.0 ± 10.7 (32, 78)

Primary prophylaxis: start G-CSF in fi rst cycle 24–72 hours after end of the fi rst chemotherapy and continue through all cycles (when appropriate as per cycle reassessment).

Secondary prophylaxis: start G-CSF if a neutropenic event was observed in the previous cycle.

0 5 10 15 20

DLBCL

Breast

Multiple myeloma

Ovarian

Lung

Bladder

Prostate

25 30 35

Table 3. CIN/FN Outcomes

Outcome Incidence (%)

CIN any Grade 9.4

CIN Grade 3 or 4 6.3

CIN Grade 4 1.6

FN 1.6

CIN/FN-related hospitalizations 1.6

CIN/FN-related chemotherapy disturbances (dose reduction, delay or cancellation)

4.7

Table 2. Zarzio® treatment patterns

Prophylaxis type Primary

Secondary

68.8%

31.2%

Prophylaxis decision Under treated

Correctly treated

Over treated

15.7%

34.3%

50.0%

Dose 30 MIU/day

48 MIU/day

47.8%

52.2%

Day of initiation During chemotherapy (day 0)

Per guidelines (day 1–3)

Late (day 4 or later)

48.1%

51.2%

0.7%

Duration 1–3 days

4–5 days

6 or more days

92.3%

7.4%

0.3%

Hb = hemoglobin; CV = cardiovascular.

Prophylaxis of chemotherapy-induced febrile neutropenia with biosimilar fi lgrastim: Description of patients, treatment patterns and

outcomes in the MONITOR-GCSF Study in RomaniaL. Miron1, M. Marinca1, I. Miron2, E. Prisacariu3

1Regional Oncology Institute Iasi, Romania , 2„Sf. Maria” Hospital Iasi, Romania, 3Sandoz Pharma Services, Romania

Presented at

CONFER 2014: The Conferences of the Iasi Regional Institute of Oncology

Iasi, Romania

27–30 November 2014