vCost-effectiveness analysis of bevacizumab and cetuximabin advanced colorectal cancer

University of CampinasCentre for Evidences in Oncology

ADRIANA CAMARGO DE CARVALHOANDRÉ DEEKE SASSE

Colorectal Cancer as a Global Problem

Third most commonly diagnosed cancer globally

Incidence

Mortality

Metastatic Colorectal Cancer

INCURABLE DISEASE25% of newly diagnosed patients50% of patients with presumable local disease

PALLIATIVE CHEMOTHERAPY PLAYS A MAJOR ROLEProlonging survivalImproving cancer-related symptoms

Historical Evolution

1990s

5FU2000s

OxaliplatinIrinotecan

2010s

BevacizumabCetuximabPanitumumab

6 month survival 12

month survival 20

month survival

Costs and Values

Sustaining the unsustainable

The high prices of cancer drugs is a big problem

All of us need to urgently engage in active, open, constructive discussions to find fair, practical, sustainable solutions

Brazil Specificities

Public Sector80%

Private Health Plans20%

Fee for service –‘packages’ (APAC)

Reimbursement

Brazil Specificities

ADOPTION OF

NEW TECHNOLOGIES

Based mostly on efficacy and effectiveness

Cost-effectiveness evaluation still in beginnings

Budgetary impact

Objective

To assess the cost-effectiveness of the combinations and sequences of chemotherapy combined with cetuximab and/or bevacizumabfor patients with advanced colorectal cancer in the Brazilian public health care setting

Methods

Software TreeAge Pro

Markov model

Compare costs and clinical outcomes

Hypothetical cohorts of mCRC patients

Life-time period

3-month cycles

Brazilian Public Health system perspective

Three different palliative treatment sequences

Chemotherapy Regimens Sequences

Strategy First Line Second Line Third Line

1 FOLFOX FOLFIRI BSC

2FOLFIRI + Cetuximab (RAS wt) or

FOLFIRI + Bevacizumab (RAS mt)

FOLFOXBSC

3 FOLFIRI + Bevacizumab

FOLFOX +/-

BevacizumabIrinotecan + Cetuximab (KRAS wt)

or BSC (KRAS mt)

FOLFOX = infusional 5-fluorouracil, leucovorin and oxaliplatinFOLFIRI = infusional 5-fluorouracil, leucovorin and irinotecanBSC = Best Supportive Care

Markov Model

Chemoterapy1st line

Chemoterapy2nd line

Chemoterapy3rd line

BSC Death

MetastaticColorrectal

Cancer

Efficacy DataHAZARD RATIO

Parameter PFS OS SourceFOLFIRI + cet vs FOLFIRI (1st line-RASwt) 0.56

(0,41-0,76)

0.69(0,54-0,88)

Crystal ASCO 2014

FOLFOX + bev vs FOLFOX (2nd Line TML) 0.68(0,59-0,78)

0.81(0,69-0,94)

Bennouna2013

Irinotecan + cetuximab vs cetuximab 0.54(0,42-0,71)

0.91(0,68-1,21)

Cunningham 2014

FOLFIRI + bev vs FOLFIRI + cet (wtRAS) 0.96(0,85-1,09)

1,08(0,91-1,28)

Venook2015

TRANSITION PROBABILITIES

Parameter Value SourceBSC to Death 0.26 Madden 2005FOLFOX 1st Line to CT2ndLine 0.0792

Goldberg 2006FOLFOX 1 st Line to BSC 0.0198FOLFOX 1 st Line to Death 0.106FOLFIRI 2ndLine to BSC 0.18

Peeters 2014FOLFIRI 2ndLine to Death 0.16Cetuximab 3rd line to BSC 0.29

Karapetis 2008Cetuximab 3rd line to Death 0.20

Quarterly Costs Estimated

Type of Spending Costs per Cycle

1st Line

FOLFOX 4,731

FOLFIRI + Cetuximab 13,133

FOLFIRI + Bevacizumab 11,346

2nd Line

FOLFOXFOLFIRI

FOLFOX + Bevacizumab

4,734

4,734

11,346

3st Line Irinotecan + Cetuximab 10,869

BSC 0,171

Death 0,122

Results Cost-effectiveness Rankings

STRATEGYCost

(US$)

Effectiveness

(LY)

ICER

(US$/LY)

1 (FOLFOX FOLFIRI) 17,329 1.25 -

3 (FOLFIRI + bev FOLFOX + bev Irinotecan + cet) 49,800 1.50 ext. dom.

2 (FOLFIRI + cet or FOLFIRI + bev FOLFOX) 51,012 1.55 112,549

*LY: Life years

Conclusions

Incorporation of monoclonal antibodies to conventional chemotherapy improves the expected survival of patients with mCRC

Strategies using bevacizumab and cetuximabin first-, second- or third- lines are not cost-effective in the Brazilian Public Health system

ICERs beyond USD 112k / LY

hypothetical Brazilian threshold 3x GDP per capita (US$27,229)

v

Thank youADRIANA CAMARGO DE CARVALHOdricamargo@hotmail.com

ANDRÉ DEEKE SASSE sasse@cevon.com.br