OsteosarcomaOsteosarcoma: :

EuramosEuramos StudyStudy

Mark BernsteinMark Bernstein

ChiefChief, Division of , Division of PediatricPediatric OncologyOncology//HematologyHematology

IWK Health Center, Halifax, CanadaIWK Health Center, Halifax, Canada

Trial Management Group Chair, Trial Management Group Chair, EuramosEuramos I I

OsteosarcomaOsteosarcoma: :

EpidemiologyEpidemiology

�� Most Most frequentfrequent primaryprimary tumortumor of of bonebone

�� 5% of 5% of malignantmalignant diseasedisease in in

adolescenceadolescence

�� Male:FemaleMale:Female 3:23:2

�� 450 450 –– 550 cases in 550 cases in NorthNorth AmericaAmerica per per

yearyear underunder 19 19 yearsyears

�� 150150--200 cases in 200 cases in thosethose 2020--29 29 yearsyears of of

ageage

�Similar

RegimensMAP- MAPI

�Similar Results

�Progress Slow

�� SimilarSimilar

RegimensRegimensMAPMAP-- MAPIMAPI

�� SimilarSimilar ResultsResults

�� Progress Progress SlowSlow

OsteosarcomaOsteosarcoma::International StudiesInternational Studies

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Osteosarcoma: 5-year survivalrates

Salvage of Salvage of poor poor

responders ?responders ?

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Osteosarcoma: Response & Survival

good (n=734)

73.4% (SE 2%)

47.2% (SE 3%)

poor (n=586)

p<.0001COSS:Bielacket al 2002

3 year EFS: good ≈≈≈≈ 70%poor ≈≈≈≈ 45%

Significance 5%Power 80%45% ⇒⇒⇒⇒ 55%

Salvage-Question Statistics

SalvageSalvage--Question Question StatisticsStatistics

Osteosarco

ma

Osteosarco

ma

EURAMOSEURAMOS

3 year EFS: good ≈≈≈≈ 70%poor ≈≈≈≈ 45%

Significance 5%Power 80%45% ⇒⇒⇒⇒ 55%

needed: ± 700 poor responders⇒ ±±±± 1400 patients

Salvage-Question Statistics

SalvageSalvage--Question Question StatisticsStatistics

Osteosarco

ma

Osteosarco

ma

EURAMOSEURAMOS

Outcome ImprovementOutcome Improvement

��Good respondersGood responders

�� 70 to 80%70 to 80%

�� Around 600 randomized Around 600 randomized

patientspatients

EuramosEuramos: Study design : Study design

�� Should postShould post--operative therapy be operative therapy be altered based on histological altered based on histological response?response?

�� Choice influenced by toxicity profile of Choice influenced by toxicity profile of medications:medications:

–– IfosfamideIfosfamide, , etoposideetoposide: bone marrow : bone marrow suppression, fever, sterility, induced suppression, fever, sterility, induced leukemia, renal dysfunctionleukemia, renal dysfunction

–– Interferon: fluInterferon: flu--like syndrome; spasticity in like syndrome; spasticity in young children, mainly infants: those less young children, mainly infants: those less than 5 years of age excludedthan 5 years of age excluded

Cisp-Dox-MTX

surgery

Good: CDM

CDM +

pegintron

CDMIE

POOR

R

A

N

D

O

M

I

Z

E

CDM: cisplatin, doxorubicin, high-dose methotrexate

POOR >10% viable tumor

OsteosarcomaOsteosarcoma, , EuramosEuramos

CDMR

A

N

D

O

M

I

Z

E

EURAMOS: Treatment SchemaEURAMOS: Treatment Schema

EURAMOS Recruitment as of August 31,

2008

EURAMOSEURAMOS Recruitment Recruitment as of August 31, as of August 31,

20082008

Courtesy of EURAMOS-CDC,

MRC London

EURAMOS Randomisation as of August

31, 2008

EURAMOSEURAMOS RandomisationRandomisation as of August as of August

31, 200831, 2008

Courtesy of EURAMOS-CDC,

MRC London

EuramosEuramos: Study problems: Study problems

�� Good responder rate higher than Good responder rate higher than predictedpredicted

�� Randomization rate lower than Randomization rate lower than predictedpredicted–– 6565--70%, not 8570%, not 85--90%90%

–– Late, at week 15Late, at week 15--1616

�� Accrual likely to be extended (to June, Accrual likely to be extended (to June, 2010)2010)

FAQsFAQs

�� Is it okay to proceed with my institutional Is it okay to proceed with my institutional

pathologist'sassessmentpathologist'sassessment or do I have to wait or do I have to wait

for Dr. for Dr. TeotTeot??

Answer: It is okay to proceed with your Answer: It is okay to proceed with your

institutional pathologistinstitutional pathologist’’s assessment. S/he s assessment. S/he

is the pathologist of record. Note: is the pathologist of record. Note:

disagreement is relatively uncommondisagreement is relatively uncommon

FAQsFAQs

�� Is it necessary to send specimens to Is it necessary to send specimens to

the BPC for Dr. the BPC for Dr. Teot'sTeot's review if we review if we

decide to proceed with our own decide to proceed with our own

institutional pathologist's assessment?institutional pathologist's assessment?

�� Answer: yesAnswer: yes