Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®

Phase 3

Completed

Conditions: Neutropenic Complications
Breast Neoplasms
Chemotherapy-induced Neutropenia
Chemotherapeutic Toxicity

Interventions: Drug: Neulasta®
Drug: LA-EP2006

Registration Number: NCT01735175

Lead Sponsor: Sandoz

Brief Summary: The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in breast cancer patients.

Detailed Description: This randomized, double-blind trial compared the proposed biosimilar LA-EP2006 with the reference Neulasta® in women (≥18 years) receiving chemotherapy for breast cancer. Therefore patients were randomized to receive LA-EP2006 (n = 159) or the reference product (n = 157) for ≤6 cycles of (neo)-adjuvant TAC (docetaxel 75mg/m\^2, doxorubicin 50 mg/m\^2, and cyclophosphamide 500mg/m\^2) chemotherapy. The primary end point was the duration of severe neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute neutrophil count \<0.5 × 10\^9/l). The equivalence was confirmed if 95% CIs were within a ±1 day margin. LA-EP2006 was equivalent to the reference product in DSN (difference: 0.07 days; 95% CI \[-0.12, 0.26\]). Further, LA-EP2006 and the reference Neulasta® showed no clinically meaningful differences regarding efficacy and safety.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 316

Inclusion Criteria

histologically proven breast cancer
eligible for six cycles of neoadjuvant or adjuvant chemotherapy

Exclusion Criteria

concurrent or prior chemotherapy for breast cancer
concurrent or prior anti-cancer treatment for breast cancer such as endocrine therapy, immunotherapy, monoclonal antibodies, and/or biological therapy
concurrent prophylactic antibiotics
previous therapy with any G-CSF (granulocyte-colony stimulating factor) product

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Neulasta®	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.
LA-EP2006	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.

Primary Outcome Measures

Name	Time	Method
Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy	21 days (Cycle 1 of chemotherapy treatment)	Mean duration of severe neutropenia, defined as number of consecutive days with ANC \<0.5 × 10\^9 cells/L (grade 4 neutropenia).

Secondary Outcome Measures

Name	Time	Method
Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles	across al cycles (18 weeks)	Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once.
Depth of ANC Nadir in Cycle 1	Cycle 1 (3 weeks)	The depth of ANC nadir was defined as the patient's lowest ANC (10\^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given.
Number of Patients With ANC Nadir Per Day in Cycle 1	Cycle 1 (3 weeks)	Numbers of patients with ANC nadir based per day during Cycle 1 are given.
Time to ANC Recovery in Days in Cycle 1	across Cycle 1 (3 weeks)	Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10\^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10\^9 cells/L are given.
Frequency of Infections by Cycle and Across All Cycles	across all cycles (18 weeks)	The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class "Infections and Infestations".
Mortality Due to Infection	Study course (41 weeks)	Number of patients with death due to infections
Incidence of Febrile Neutropenia (FN)	across all cycles (18 weeks)	FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) \< 0.5 × 10\^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN ("febrile neutropenia", "neutropenic sepsis") were taken into account.