Pegfilgrastim, injection, 6 mg in 0.6 mL single use pre-filled syringe, Neulasta®, November 2008
Public summary document for Pegfilgrastim, injection, 6 mg in 0.6 mL single use pre-filled syringe, Neulasta®, November 2008
Page last updated: 24 March 2009
Public Summary Document
Product: Pegfilgrastim, injection, 6 mg in 0.6 mL
single use pre-filled syringe, Neulasta®
Sponsor: Amgen Australia Pty Ltd
Date of PBAC Consideration: November 2008
1. Purpose of Application
To extend the current Section 100 (Highly Specialised Drug) listing
for pegfilgrastim as primary prophylaxis to include chronic
lymphocytic leukaemia (CLL) patients treated with fludarabine and
cyclophosphamide (FC).
2. Background
At the September 2002 meeting, the PBAC recommended a Section 100
listing for pegfilgrastim for the same indications as filgrastim on
a cost-minimisation basis compared with filgrastim. Single dose
pegfilgrastim 6 mg was considered to be of similar efficacy and
safety to filgrastim 5 micrograms/kg per day (as used on the PBS)
for an average of 11.25 days. Pegfilgrastim was listed effective 1
February 2003.
In July 2008 the PBAC furthermore reaffirmed its previous statement
that it would flow-on any future new PBS-eligible patient
populations recommended for pegfilgrastim to filgrastim because
continuing flexibility in treatment options for the prophylaxis of
chemotherapy induced febrile neutropenia is an important objective.
The Committee acknowledged that the sponsor has no objection to
this.
3. Registration Status
Pegfilgrastim is TGA registered for the following indications:
- Treatment of patients with cancer following chemotherapy, to decrease the duration of severe neutropenia and so reduce the incidence of infection, as manifested by febrile neutropenia.
4. Listing Requested and PBAC’s View
Section 100 Highly Specialised Drugs Program
Private hospital authority required
For use in a patient undergoing induction and consolidation therapy for acute myeloid
leukaemia;
A patient with breast cancer receiving standard dose adjuvant chemotherapy who have
had a prior episode of febrile neutropenia or prolonged severe neutropenia (neutrophil
count of less than 1,000 million cells per litre), and for whom there is clinical
justification for wishing to continue therapy with the same drug combination, dosage
and treatment schedule, and for whom a good response to treatment is anticipated providing
chemotherapy can be delivered as planned;
A patient receiving first-line chemotherapy for Hodgkin's disease who have had a prior
episode of febrile neutropenia or prolonged severe neutropenia (neutrophil count of
less than 1,000 million cells per litre), and for whom there is clinical justification
for wishing to continue therapy with the same drug combination, dosage and treatment
schedule, and for whom a good response to treatment is anticipated providing chemotherapy
can be delivered as planned;
A patient receiving chemotherapy for myeloma who have had a prior episode of febrile
neutropenia, and for whom there is clinical justification for wishing to continue
therapy with the same drug combination, dosage and treatment schedule, and for whom
a good response to treatment is anticipated providing chemotherapy can be delivered
as planned.
Section 100 Highly Specialised Drugs Program
Private hospital authority required
A patient being treated with aggressive chemotherapy with the intention of achieving
a cure or substantial remission in:
a. acute lymphoblastic leukaemia; or
b. breast cancer (adjuvant chemotherapy with docetaxel in combination with an anthracycline and cyclophosphamide); or
c. germ cell tumours; or
d. infants and children with CNS tumours; or
e. neuroblastoma; or
f. non-Hodgkin lymphoma (aggressive grades; or low grade receiving an anthracycline-containing regimen); or
g. relapsed Hodgkin disease; or
h. sarcoma; or
i. chronic lymphocytic leukaemia treated with fludarabine and cyclophosphamide.
For PBAC’s view, see Recommendation and Reasons.
5. Clinical Place for the Proposed Therapy
To provide primary prophylaxis for an aggressive, highly myelotoxic
chemotherapy regimen (FC) intended to achieve a cure or substantial
remission, and thus reduce avoidable toxicity and/or suboptimal
dosing.
6. Comparator
The submission did not nominate a comparator.
7. Clinical Trials
The submission referred to two key randomised controlled trials
using FC in advanced CLL patients; CLL4 (Catovsky, 2007) and US
Intergroup trial (Flinn, 2007) to demonstrate that FC is an
aggressive regimen resulting in substantial remission.
The trials published at the time of submission are as follows:
| Trial/First author | Protocol title/Publication title | Publication citation |
| Catovsky 2007 | Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukemia (the LRF CLL4 Trial) | Catovsky D, Richards S, Matutes E et al. The Lancet 2007; 370; issue 9583: 230-239. |
| Flinn 2007 | Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia | Flinn I, Neuberg D, Grever M et al Journal of Clinical Oncology 2007; 25(7):793-98. |
8. Results of Trials
In CLL4 filgrastim was used as secondary prophylaxis i.e. following
severe neutropenia. There were three septic deaths reported and
febrile episodes occurred in 35 % of patients receiving FC. In the
US Intergroup trial, primary prophylaxis was mandated for all
patients receiving FC. There were no septic deaths reported in the
study and the incidence of neutropenic complications reported was
lower than in CLL4.
The submission claimed that as CLL is closely related to low grade
Non-Hodgkin Lymphoma (NHL) and FC is considered to be at least
myelotoxic as CHOP (Leporrier, 2001). The submission claimed that
the results of the economic model presented to the PBAC when
considering the pegfilgrastim low grade NHL submission (March 2007)
are likely to be comparable to those for FC in CLL.
The submission requested a primary prophylaxis listing for use with
FC in CLL patients on the basis of clinical need and to ensure
equity of access and consistency with current listings.
For PBAC’s view, see Recommendation and
Reasons.
9. Clinical Claim
The submission claimed that without granulocyte-colony stimulating
factor (G-CSF) support, half to two thirds of neutropenic
complications occur in the first cycle of FC, comparable to other
chemotherapy regimens for which G-CSFs are PBS listed as primary
prophylaxis, and that where the risk of febrile neutropenia is
high, the benefits are greatest when primary prophylaxis is
given.
For PBAC’s view, see Recommendation and
Reasons.
10. Economic Analysis
The submission did not present an economic evaluation.
11. Estimated PBS Usage and Financial Implications
The submission used an epidemiological approach to estimate the
financial implications of a PBS listing for pegfilgrastim as
prophylaxis with CLL treated with FC.
The submission stated the incidence rate for CLL had remained
relatively constant over time, and it was estimated that the number
of CLL patients would be less than 10,000 per year from Year 1 of
listing to Year 5 of listing.
The submission predicted that the extent of use of FC in CLL would
vary, with more patients receiving FC with primary prophylaxis
support than with secondary prophylaxis than with no G-CSF support.
It was assumed that a primary prophylaxis listing would result in
75 % of eligible patients receiving FC and with a secondary listing
65 % of eligible patients receiving FC. It was also assumed that 40
% of patients would receive a second course of FC, and that the
average period between courses is 4 years.
The submission stated that from FC trials the average number of FC
cycles per course was 4.6, and thus assumed that for a primary
prophylaxis listing patients would receive 4.6 cycles of
pegfilgrastim per course, and for a secondary prophylaxis listing,
assuming pegfilgrastim commences from cycle 2, 3.6 cycles of
pegfilgrastim.
The submission estimated the cost of pegfilgrastim to the PBS as
primary prophylaxis, assuming an uptake rate of 75% and 4.6 cycles
per patient as less than $10 million in Year 1, increasing to 95%
uptake, 4.6 cycles and less than $10 million in Year 5. The
estimated cost of pegfilgrastim to the PBS as secondary
prophylaxis, assuming an uptake rate of 65% and 3.6 cycles per
patient, as less than $10 million in Year 1 and Year 5 with the
same uptake rate and number of cycles.
The submission claimed that use of primary prophylaxis would result
in cost savings due to the reduction in the number of febrile
neutropenic events compared to no G-CSF. The estimated cost saving
in the submission for primary prophylaxis was less than $10 million
per year, and for secondary prophylaxis a corresponding saving of
less than $10 million yearly.
12. Recommendation and Reasons
The PBAC recommended extending the currently recommended PBS listing for pegfilgrastim
to include the secondary prophylaxis of neutropenia or prolonged severe neutropenia
for patients with chronic lymphocytic leukaemia (CLL) who are being treated with fludarabine
and cyclophosphamide (FC) and that this recommendation should also apply to the current
listing for filgrastim. The PBAC noted it had considered a previous submission to
list fludarabine in combination with cyclophosphamide for the treatment of CLL to
be cost-effective and that the cost-effectiveness analysis of the submission had included
the cost of colony stimulating factors for secondary prophylaxis.
However, the PBAC noted that no data were presented to support use of pegfilgrastim
in the primary prophylaxis setting and therefore the PBAC did not support use in this
setting. The PBAC considered that myelotoxicity from FC was more likely to be cumulative
and that the rate of fever due to neutropenia in cycle 1 with FC was not sufficiently
frequent compared with other chemotherapy regimens like CHOP, used for the treatment
of non-Hodgkin lymphoma, to warrant primary prophylaxis. However, a primary prophylaxis
listing could be considered if data were presented showing that there was a high incidence
of febrile neutropenia in cycle 1 of FC.
Recommendation
PEGFILGRASTIM, injection, 6 mg in 0.6 mL, single use pre-filled syringe, Neulasta®, Amgen Australia. (6.15)
Restriction:
Section 100 (Highly Specialised Drugs Program)
Private Hospital Authority Required
For use in a patient undergoing induction and consolidation therapy for acute myeloid
leukaemia;
A patient with breast cancer receiving standard dose adjuvant chemotherapy who have
had a prior episode of febrile neutropenia or prolonged severe neutropenia (neutrophil
count of less than 1,000 million cells per litre), and for whom there is clinical
justification for wishing to continue therapy with the same drug combination, dosage
and treatment schedule, and for whom a good response to treatment is anticipated providing
chemotherapy can be delivered as planned;
A patient receiving chemotherapy for B-cell chronic lymphocytic leukaemia with fludarabine
and cyclophosphamide who has had a prior episode of febrile neutropenia or prolonged
severe neutropenia (neutrophil count of less than 1,000 million cells per litre),
and for whom there is clinical justification for wishing to continue therapy with
the same drug combination, dosage and treatment schedule, and for whom a good response
to treatment is anticipated providing chemotherapy can be delivered as planned.
A patient receiving first-line chemotherapy for Hodgkin's disease who have had a prior
episode of febrile neutropenia or prolonged severe neutropenia (neutrophil count of
less than 1,000 million cells per litre), and for whom there is clinical justification
for wishing to continue therapy with the same drug combination, dosage and treatment
schedule, and for whom a good response to treatment is anticipated providing chemotherapy
can be delivered as planned;
A patient receiving chemotherapy for myeloma who have had a prior episode of febrile
neutropenia, and for whom there is clinical justification for wishing to continue
therapy with the same drug combination, dosage and treatment schedule, and for whom
a good response to treatment is anticipated providing chemotherapy can be delivered
as planned.
Section 100 Highly Specialised Drugs Program
Private hospital authority required
A patient being treated with aggressive chemotherapy with the intention of achieving
a cure or substantial remission in:
a. acute lymphoblastic leukaemia; or
b. breast cancer (adjuvant chemotherapy with docetaxel in combination with an anthracycline and cyclophosphamide); or
c. germ cell tumours; or
d. infants and children with CNS tumours; or
e. neuroblastoma; or
f. non-Hodgkin lymphoma (aggressive grades; or low grade receiving an anthracycline-containing regimen); or
g. relapsed Hodgkin disease; or
h. sarcoma.
Pack size: 1
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be
subsidised in Australia. It considers submissions in this context.
A PBAC decision not to recommend listing or not to recommend
changing a listing does not represent a final PBAC view about the
merits of the medicine. A company can resubmit to the PBAC or seek
independent review of the PBAC decision.
14. Sponsor’s Comment
The sponsor had no comment.
