treatment of rare cancers the physician’s...

Treatment of rare cancers

The physician’s perspective

Paolo G. Casalipaolo.casali@istitutotumori.mi.it

Eur J Cancer 2011;47:2493

Casali PG et al, 2012, submitted

Nat Med 2010;9:363

Malakoff D, Science 2011;331:1545

Rare Tumours in Europe

CHALLENGES AND SOLUTIONS6 November 2008 - Brussels

Rare Tumours in Europe

CHALLENGES AND SOLUTIONS

A

B

cure

cure

Uncertainty

=

0-1

0-1

Risk

A

B

cure

cure

N Engl J Med 1987;316:250

risk

probability

subjectiveprobability

objectivefrequency

degree of belief

P[E]

The notion of probability

Evidence from clinical studies…

Mr. Bayes & Mr. Price. Phil Trans 1763;53:370

P[A|B] = P[A] x P[B|A]P[B]

The Bayes theorem…

Mr. Bayes & Mr. Price. Phil Trans 1763;53:370

BMJ 2003;327:47

BMJ 2003;327:47

Posterior

probability distribution

Skeptical / optimistic

sensitivity analysis

The preclinical rationale

Prior probability

� clinical decision-making

� methods to combine evidence

� new study designs

� surrogate end points

� organization of studies

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 3 6 9 12 15 18 21 24

∆∆∆∆

p <0.05

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 3 6 9 12 15 18 21 24

∆∆∆∆

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 3 6 9 12 15 18 21 24

∆∆∆∆

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 3 6 9 12 15 18 21 24

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 3 6 9 12 15 18 21 24

Generalizability…

one size fits all?

Quality of evidence

Surrogate end-points

T activity(cancer outcomes)

efficacy(patient outcomes)

Surrogate end points

Karnofsky DA, 1961;6:709

Booth CM et al. Eur J Cancer 2008;44:25

Collaborative networks

Prospective clinical data bases

/ observational studies

P >0

=

new drug

best supportive care

U >0

Compassionate and off-label

use of drugs

“Orphan drugs”

� 10-year marketing exclusivity� fee reductions and exemptions� protocol assistance� national incentives� EU-funded research

Registration risk

Inequalities in cancer care

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 3 6 9 12

EU regulator National regulator

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 3 6 9 12

New drugs:

approval vs reimbursement

Pharma

Researchers

Pharma

RegulatorsResearchers

Pharma

RegulatorsResearchers

Paolo G. Casalipaolo.casali@istitutotumori.mi.it