Approche multidisciplinaire dans le traitement du cancer

du rein métastatique

Approche multidisciplinaire dans le traitement du cancer

du rein métastatique

Pierre I. Karakiewicz, MD, MPHUrologic Oncologist,

Associate Professor andSenior Research Scientist,

Director, Cancer Prognostics and Health Outcomes UnitUniversity of Montreal Health Center (CHUM)

Pierre I. Karakiewicz, MD, MPHUrologic Oncologist,

Associate Professor andSenior Research Scientist,

Director, Cancer Prognostics and Health Outcomes UnitUniversity of Montreal Health Center (CHUM)

Canadian cancer facts and figures 2007

Canadian cancer facts and figures 2007

Cancer incidence and mortality 2007 Cancer incidence and mortality 2007

Incidence

Mortality

6th

10th

Five year cancer survivalFive year cancer survival

RCC Stage vs. prognosisRCC Stage vs. prognosis

Cohen HT, McGovern FJ. N Engl J Med. 2005;353:2477-2490.

Stage I

Tumor < 7 cm in greatest dimension and limited to kidney; 5-year survival, 95%

Stage II

Tumor > 7 cm in greatest dimension and limited to kidney; 5-year survival, 88%

Stage III

Tumor in major veins or adrenal gland, tumor within Gerota’s fascia, or 1 regional lymph node involved; 5-year survival, 59%

Stage IV

Tumor beyond Gerota’s fascia or > 1 regional lymph node involved; 5-year survival, 20%

Histology Type % Prognosis Gene

Clear cell 85 Poor VHL

Papillary Type I Papillary Type 2

55

Good Poor

MET, FH, TFE3

Chromophobe 3 Good BHD

Oncocytoma 4 Good BHD

Collecting duct < 1 Poor None known

Sarcomatoid / Other 1–2 Poor None known

Tumor histology vs. prognosisTumor histology vs. prognosis

1. Cohen HT, McGovern FJ. N Engl J Med. 2005;353:2477-2490.2. Cangiano T, Liao J, Naitoh J, et al. J Clin Oncol. 1999;17:523-528.

3. Nelson EC, Evans CP, Lara PN Jr. Cancer Treat Rev. 2007;33:299-313.

Caucasian 85%

Other 15%

SEER RCC demographicsSEER RCC demographicsFemale 38%

Male 62%

Temporal distribution of new RCC diagnoses – all stages SEER

Temporal distribution of new RCC diagnoses – all stages SEER

N=43143

RN 66% PN 7%

No Sx 25%LTD 1%

Rx type

T1-2,N0,M059%

T3-4,N0-2,M019%

M1 22%

Stage

FG 1 20%

FG 2 46%

FG 3 26%

FG 4 8%Grade

Clear cell RCC 85%

Other Histology

SEER Rx by stageSEER Rx by stage

RN 80%

PN 12%No Sx 7%LTD 1%

T1-2, N0, M0

RN 89%

PN 3%No Sx 8%LTD <1%

T3-4, N0-2, M0

RN 28%

PN 1% No Sx 71%

LTD <1%M1

Modes of presentation: locally advanced RCC

Modes of presentation: locally advanced RCC

Nephrectomy rate T3-4, N0-2, M0 RCCNephrectomy rate

T3-4, N0-2, M0 RCC

N=7068n= 6786Range 96.2- 95.7%Χ2 trend p=0.2

Matched:HR 5.1 p<0.001CRR p<0.001

84 months

11 vs. 8 months

17 vs. 7 months

Cohen HT, McGovern FJ. N Engl J Med. 2005;353:2477-2490.

Overall survival RCC specific survival10

months

10 months

n=5372SEER 9: 1988-2004

MVA HR 2.4 p<0.001

CRR p<0.001

Cohen HT, McGovern FJ. N Engl J Med. 2005;353:2477-2490.

Temporal trendsCytoreductive nephrectomy - SEER

Temporal trendsCytoreductive nephrectomy - SEER

N=5372n= 2925Range 56.4- 51.1%Χ2 trend p=0.8

N=2530 N=1377

31

Final Overall SurvivalFinal Overall Survival

0 3 6 9 12 15 18 21 24 27 30 33 36Time (months)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Ove

rall

Surv

ival

Pro

babi

lity

Sunitinib (n=375) Median: 26.4 months (95% CI: 23.0 - 32.9)IFN-α (n=375)

Median: 21.8 months (95% CI: 17.9 - 26.9)

Hazard Ratio = 0.821(95% CI: 0.673 - 1.001)p =0.051 (Log-rank)

375 44 / 326 38 / 283 48 / 229 42 / 180 14 / 61 4 / 2nDeath/nRisk Sunit375 61 / 295 46 / 242 52 / 187 25 / 149 15 / 53 1 / 1nDeath/nRisk IFN-α

Total DeathSunitinib 190IFN-α 200

Total DeathSunitinib 190IFN-α 200

0

20

40

60

80

100

0 2 4 6 8 10 12 14Months

Prob

abili

ty, %

Everolimus (n = 277)Placebo (n = 139)

Hazard ratio = 0.3395 % CI [0.25, 0.43]

Median PFSEverolimus: 4.90 moPlacebo: 1.87 mo

Log rank P value = <0.001

Patients at riskEverolimusPlacebo

277 192 115 51 26 10 1 0139 47 15 6 2 0 0 0

> 25 %

3 mos

Baseline Month 17

Stable Disease to Everolimus Therapy

Stable Disease to Everolimus Therapy

Modes of presentation: metastatic RCCModes of presentation: metastatic RCC

Sequential therapy: PFS projections

• Surgery: 10 months• Sunitinib: 8 months• Sorafenib: 3 months• Avastin: 5 months• Torisel: 3 months• Evorolimus: 3 months

• Total: 32 months

• Overall survival: 32++ months

Sequential therapy: PFS projections

• Surgery: 10 months• Sunitinib: 8 months• Sorafenib: 3 months• Avastin: 5 months• Torisel: 3 months• Evorolimus: 3 months

• Total: 32 months

• Overall survival: 32++ months

40