Transcript Endometrial Cancer - Gold Coast Cancer Care

ENDOMETRIAL CARCINOMA
UPDATES
Dr Marco Matos
Gold Coast Cancer Care, Gold Coast University
Hospital and Pacific Private Oncology Group
USA. Uterine cancer: new cases and dates
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1990
33000
4000
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2000
36100
6500
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2010
43470
7950
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Ovarian cancer 21880 new cases and 13850 deaths
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Cervical cancer: 12200 new cases and 4210 deaths
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In Australia endometrial cancer
affects 1 in 69 women before the age
of 75.
In 2010, 2100 women were
diagnosed. 6 /day
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370 expected deaths a year
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The incidence is increasing
Obesity significantly
increases the risk of
developing cancers including
endometrial cancer
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In 2020, more than 70% of the population of Australia will be
overweight
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Non endometrioid (serous, clear cell carcinoma) cancers
disproportional contribute to deaths in comparison with endometrioid
histology
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Carcinogenesis model of type I endometrial cancer: PTEN, MSI and Kras alterations playing an earlier important role. P53 mutations a late
event
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Carcinogenesis model of type II endometrial cancer: P53 mutation an
early event
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Molecular alterations differ in Type 1 vs type 2
endometrial cancers
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Endometrioid adenocarcinoma (Type 1)
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PTEN loss of function (up to 60%)
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PI3KCA mutation (30%)
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K ras mutation (10- 20%)
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FGFR2 mutations (12- 16%)
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Microsatelalite instability (20 – 45%)
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Nuclear accumulation of b- cadherin (18 – 47%)
Papillary Serous (Type 2)
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P53 mutations (90%)
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MANAGEMENT
Survival improves in the hands of a trained Gynae-oncologist
Hormonal therapy of endometrial cancer
Agent
Tumour
grade
Number
RR %
Medroxyprogesterone 800 mg/d
Podratz 1985
1
2
3
14
17
27
40
15
2
Tamoxifen 40 mg/d alternating with
medroxyprogesterone 200mg/d
Whitney 2003
1
2
3
15
17
27
33
Medroxyprogesterone 160 mg/d x 3 weeks then
Tamoxifen 40 mg /d x 3 weeks
Fiorica 2003
1
2
3
16
17
22
38
24
22
Response rates and survival to single agent
chemotherapy
AGENT
Prior
treatment
Number
RR%
Prob PFS
(>6 mo)
OS
months
25
0
0.08
8.7
48
25
0.21
8.9
Caelyx
43
9
0.23
8.2
Topotecan
28
7
0.25
9
Oxaliplatin
52
13
0,27
10.9
27
8
0.11
6.4
27
4
0.28
9.4
50
12
0.20
8.7
Etoposide
Paclitaxel
Docetaxel
No
77% prior
Rx
Pemetrexed
Ixabepilone
94% prior
Rx
Biological agents: response rate and PFS
Agent
N
RR
%
Prob
(PFS> 6 mo)
Clinical
Benefit
Ratio (CR +
PR +SD)
Duration of
stability
(median
months)
TKI and VEGF inhibitors
Gefitinib
29
3.8
0.15
Lapatinib
30
3.3
0.10
Bevacizumab
52
13.5
0.40
Temsirolimus
18
25
82
6.7
Temsirolimus
27
7
51
3.8
Deferolimus
45
7
33
<4
Everolimus
35
0
43
4.5
MTOR inhibitors
LET’S LOOK AT THE DATA:
GOG 30
Adryamicin in advanced / recurrent
endometrial cancer
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Adryamicin 60 mg/m2
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N = 43
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CR= 26 % + PR= 12% = 37%
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Better survival for responders, p<.05
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Active agent
GOG 34
Phase III, surgery + radiotherapy +Doxorubicin in stage IC, II and IIIA EC
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Doxo 60 mg/m2 q 3 /52 up to 500 mg
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No G 3 – 4 cardio toxicity
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Survival 60 vs 66%, p= NS
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“Unable to determine effect”
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Morrow et al Gyn Onc 36: 166, 1990
GOG 99
Surgery +- adjuvant
radiotherapy
GOG 107
phase III trial, doxorubicin +- cisplatin in stage
III/ IV EC
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Doxo 60 +- CDDP 50 mg/m2 q 3/52
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N= 281
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G3-4 leucopenia (62 vs 40%), anaemia (22 vs 4%), N/V (13
vs 4%)
Dox; CR 8%+ PR 17%= 25%, PFS 3.9 mo, OS 9 mo
Dox + CDDP; CR 19% + PR 23% = 42%, PFS 5.7 mo , OS
9.2 mo
Adding cisplatin improves RR and PFS but not OS at the
cost of more toxicity
GOG 122
Adjuvant Radiotherapy vs AP
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Adverse events were more common with AP
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At 24 mo: p<0.01:
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DFS: WART 46 vs AP 59%,
OS: WART 59% vs AP 70%
GOG 177
RR: 57 VS 34%, PFS 8.3 vs 5.3, mOS
15.3 vs 12.3mo all in favour of TAP but
at increased neurotoxicity
GOG 184
OTHER UPDATES
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