Madrid March 6-7 14th 2015 -...

Anaemia, Neutropenia,

Thrombocytopenia,

Hemostasis and Cancer

14th ANNUAL COURSEMadrid March 6-7

2015

Updated Anaemia Guidelines: ASH NICE ESMO

M. Aapro

COI

Dr Aapro is a consultant for

Amgen, BMS, Celgene, Eisai, Genomic Health, GSK, Helsinn, Hospira, JnJ Novartis, Merck, Merck Serono,

Pfizer, Pierre Fabre, Roche, Sandoz, Teva, Vifor

and has received honoraria for lectures at symposia of

Amgen, Bayer Schering, Cephalon, Eisai, Genomic Health, GSK, Helsinn, Hospira, Ipsen, JnJ

OrthoBiotech, Merck, Merck Serono, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Teva, Vifor

No responsibility accepted for

involuntary errors or omissions.

The list may be incomplete, and does not reflect consultancy for

NGOs, Universities, Governmental agencies, and others

EORTC Guidelines for Erythropoietic

Proteins in Anaemic Patients with Cancer

revisited

Bokemeyer et al. Eur J Cancer. 2007;43:258–270

THIS DRAFT IS BASED ON THE 2014

SLIDE SET

Erythropoiesis-Stimulating

Agents – ESAs:

The 2015 ESMO guidelines

ENTER YOUR NAMEon behalf of

Authors, et al

DRAFT

THIS IS A DRAFT PUT ON TOP OF

THE « OFFICIAL EORTC » SLIDE SET OF 2007 revised 2015


SLIDE SET

Guidelines for Treatment of

Anaemia

in Patients with Cancer

The 2015 ESMO guidelines

ENTER YOUR NAMEon behalf of

Authors, et al

DRAFT

THIS IS A DRAFT PUT ON TOP OF

THE « OFFICIAL EORTC » SLIDE SET OF 2007 revised 2015

From ESMO 2010 GUIDELINES

The European Medicines Agency (EMEA) labels the use of ESAs as follows:

In patients treated with chemotherapy and an Hb level of <10 g/dl, treatment with ESAs might be considered to increase Hb to < 12 g/dl or to prevent further decline in Hb [II, A].

In patients treated with curative intent, ESAs should be used with caution [D].

Treatment recommendations according to label can be followed if there is no suspicion of functional iron deficiency (ferritin >100 ng/ml and TFS saturation <20%).

Guidelines for Treatment

of Anaemia in Patients with Cancer

“We confirm that QoL can be significantly

improved in anaemic cancer patients following

treatment of anaemia”

The two major goals of anaemia therapy are

prevention of transfusions and improvement

of QoL (grade A).

Cochrane meta-analysis on EPOs and QOL

Guidelines for Treatment of Anaemia in Patients with

Cancer

• Additional causes of anaemia should be

corrected prior to erythropoietic protein

therapy

• ……… iron deficiency ( absolute or

functional ) , bleeding, vitamin B12 or

folate deficiency, nutritional defects or

haemolysis


SLIDE SET


Cancer

*Unchanged from 2004 to 2006 to 2007 changed 2012

Guidelines and Recommendations

1. NCCN V.2.2014; 2. Rizzo, Blood 2010; 3. Schrijvers, Ann Oncol 2010; 4. Bokemeyer, EJC 2007;43:258; 5. Aapro, Oncologist 2008

NCCN

(2013/14)1 NEW

ASH/ASCO

(2010)2

ESMO

(2010)3

EORTC /

REVISION

SUGGESTION

T (2007)2,3

Expert opinion

(2012)4

Iron monitoringPrior to ESA

therapy

Baseline and

periodic monitoring

Baseline and

periodic monitoring

Baseline and

prior ESA

therapy

Prior to ESA therapy

and before each

chemotherapy cycle

Iron parameter TSAT, sF TSAT, sF TSAT or sF Not defined TSAT or sF

ID Definition

AID: sF <30 ng/mL,

TSAT <20%

FID: sF 30-800

ng/mL, TSAT 20-

50%

Not defined Not defined

FID: TSAT

<20%; ferritin

≥100* ng/mL

AID: Ferritin

<100* ng/mL;

TSAT <20%

*in high CRP

FID: high hepicidin;

TSAT <20%; ferritin

≥100 ng/mL

AID: low hepicidin;

Ferritin <100 ng/mL;

high hepicidin;

TSAT <20%

Iron supplement

AID: I.V. or oral iron

FID: I.V. iron added

to ESA

In various

scenarios, I.V. iron

mentioned as

preferred route

ID correction

Consider I.V. iron to

reduce ESA need,

but not as standard

of care

In patients with IDA

I.V. iron stated to

increase Hb more

than oral iron

ID correction

AID & FID: I.V.

iron preferred

No response

with oral iron in

patients with

active cancer

and chemo

i.v. iron is superior to

oral iron

I.V. iron dosing

IS: 200mg Q2 - 3W*

FG: 8x 125 mg QW*

LMWID: 100 mg

QW or TDI

(*1000 mg total

dose)

No dosing

recommendation

No dosing

recommendation

When possible

1000 mg

maximum

No dosing

recommendation

1. NCCN V.2.2014; 2. Rizzo, Blood 2010; 3. Schrijvers, Ann Oncol 2010; 4. Bokemeyer, EJC 2007;43:258; 5. Aapro, Oncologist 2008; 6. Aapro M et al. Ann Oncol (2012) .


Cancer

• Patients under chemotherapy whose Hb level is

below 8 g/dL should be evaluated for need of

transfusions, in addition to ESAs ( if chemo ) and

iron

There are no convincing studies

indicating that patients treated in

the curative setting with

chemotherapy should be excluded

from treatment with ESAs as per

label, with any specific pathology

Guidelines for Treatment of Anaemia in Patients with Cancer

MDS will be included in the recommendations


Cancer

• Discussion of Tx risk

• Tx data are not at the level of

registration for any drug


The target Hb concentration (Grade B)

is about 12 g/dl


The target Hb concentration (Grade B)

is about 12 g/dl

NO CHANGE…but point out some meta-analyses

( darbo, epoetin beta ) do not show an increased risk with an absolute

higher level, but actually responding patients do better ( darbo analysis )

This limit is related to lack of data of symptom benefit and

further transfusion avoidance above this Hb level


Cancer

When using erythropoietic proteins to treat

anaemia in cancer patients, the combined

analysis of all study data indicates an

approximately 1.6-fold increased risk of

thromboembolic events (grade A).


Cancer

When using erythropoietic proteins to treat

anaemia in cancer patients, the combined

analysis of all study data indicates an

approximately 1.6-fold increased risk of

thromboembolic events (grade A).

List of risk factors and prevention of

thrombo-embolic events

(LWMH use as per existing ESMO guidelines )


Cancer

USE THE AGENTS ACCORDING TO

LABEL

SPECIFIC SECTION ON BIOSIMILARS

and ALL « EPOs »

THAT ARE APPROVED BY EMA

Recombinant erythropoietins approved in the EU

European Medicines Agency. http://www.ema.europa.eu/ema/. Accessed 16 January 2015

Compound Drug

First generation

Epoetin beta NeoRecormon®

“Biosimilar epoetin alfa”

Epoetin alfa

Hexal®

Abseamed®

Binocrit®

Epoetin delta Dynepo® ??

Epoetin zetaRetacrit®

Silapo®

Epoetin thetaEporatio®

Biopoin®

Second

generation

Darbepoetin alfa Aranesp®

Methoxy polyethylene

glycol-epoetin betaMircera®

http://www.ema.europa.eu/ema/

ESA Treatment Recommendations

Doses of ESAs according to ESMO and/or based on EMA label

Epoetin alpha zeta*1 Epoetin beta1 Darbepoetin alpha1 Epoetin theta2

Initial dose 150 IU/kg sc tiw or

450 IU/kg qw

30,000 IU sc qw 2.25 mg/kg sc qw

500 mg (6.75 mg/kg) sc

q3w

20,000 IU sc qw

Dose

increase

300 IU/kg sc tiw 60,000 IU sc qw Not recommended If Hb rise

<1g/dl/4weeks: 40,000

IU qw

If Hb rise insufficient

after 4weeks: 60,000 IU

qw

Dose

reduction

If result achieved: 25-

50%

If Hb>12g/dl: 25-50%

If Hb rise

>2g/dl/4weeks: 25-

50%


50%

If Hb>12g/dl: 25-50%

If Hb rise

>2g/dl/4weeks: 25-50%


50%

If Hb>12g/dl: 25-50%

If Hb rise

>2g/dl/4weeks: 25-50%

If Hb>12g/dl: 25-50%

If Hb rise

>2g/dl/4weeks: 25-50%

Dose

withholding

If Hb>13 g/dl until

12g/dl

If Hb>13 g/dl until

12g/dl

If Hb>13 g/dl until

12g/dl

If Hb>13 g/dl until

12g/dl

sc, subcutaneous; tiw, thrice weekly; qw, once weekly; q3w, once every 3 weeks.

1. Schrijvers D, et al. Ann Oncol. 2010;21 Suppl 5:v244-v247; *2. European Medicines Agency. Eporatio – Summary of Product Characteristics.

Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001033/WC500043300.pdf

Accessed 09 February 2015

Chemotherapy-induced anaemia

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001033/WC500043300.pdf


Correct causes of anaemia

other than cancer

Consider

ESA/iron

treatment

Consider ESA/iron

treatment according

to individual factors

Including risk of

rapid worsening of

asnemia

Evaluate for

transfusion need

and consider

ESA/iron

treatment

according to

individual factors

Individualise treatment to

maintain target Hb with minimal

amount of treatment

Normal Hb

levels

Symptomatic

Hb 8-10 g/dL*

Asymptomatic

Hb ≤ 11.9 g/dL

Hb <8 g/dL

Treat to target

about 12 g/dL

Prophylactic

treatment

not

recommended

* 8-10: in some cases Tx is needed

ESA only if Hb < 10.0

or per country specific label

A NICE POSITION

AGO ( German )

Guidelines for Treatment of Anaemia in

Patients with Cancer

• Clinical trials have established that– PARENTERAL IRON HAS IMPROVED ESA REPONSE AND

REDUCED ESA DOSE

– IV IRON ALONE has shown Hb response in cancer patients

receiving chemotherapy

– ESAs decrease transfusion needs

– Hb levels are sustained on ESAs, not with intermittent transfusions

– ESAs increase quality of life in patients with symptoms related to

anemia

– ESAs should be used within guidelines

– In pts with CIA there is no convincing evidence for tumour

progression or negative impact on survival

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