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 ● ● ● ● Ovarian cancer new cases and deaths ● Cervical cancer: new cases and 4210 deaths

● In Australia endometrial cancer affects 1 in 69 women before the age of 75. ● In 2010, 2100 women were diagnosed. 6 /day ● 370 expected deaths a year ● The incidence is increasing

[TITLE] Obesity significantly increases the risk of developing cancers including endometrial cancer

[TITLE] In 2020, more than 70% of the population of Australia will be overweight

[TITLE] 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 K- ras alterations playing an earlier important role. P53 mutations a late event

[TITLE] Carcinogenesis model of type II endometrial cancer: P53 mutation an early event

Molecular alterations differ in Type 1 vs type 2 endometrial cancers ● Endometrioid adenocarcinoma (Type 1 ) – PTEN loss of function (up to 60%) – PI3KCA mutation (30%) – K ras mutation (10- 20%) – FGFR2 mutations (12- 16%) – Microsatelalite instability (20 – 45%) – Nuclear accumulation of b- cadherin (18 – 47%) ● Papillary Serous (Type 2) – P53 mutations (90%)

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MANAGEMENT

Survival improves in the hands of a trained Gynae-oncologist

Hormonal therapy of endometrial cancer AgentTumour grade NumberRR % Medroxyprogesterone 800 mg/d Podratz Tamoxifen 40 mg/d alternating with medroxyprogesterone 200mg/d Whitney Medroxyprogesterone 160 mg/d x 3 weeks then Tamoxifen 40 mg /d x 3 weeks Fiorica

Response rates and survival to single agent chemotherapy AGENTPrior treatment NumberRR%Prob PFS (>6 mo) OS months Etoposide PaclitaxelNo Caelyx Topotecan Oxaliplatin52130, Docetaxel77% prior Rx Pemetrexed Ixabepilone94% prior Rx

Biological agents: response rate and PFS Agent NRR % Prob (PFS> 6 mo) Clinical Benefit Ratio (CR + PR +SD) Duration of stability (median months) TKI and VEGF inhibitors Gefitinib Lapatinib Bevacizumab MTOR inhibitors Temsirolimus Temsirolimus Deferolimus45733<4 Everolimus

LET’S LOOK AT THE DATA:

GOG 30 Adryamicin in advanced / recurrent endometrial cancer ● Adryamicin 60 mg/m2 ● N = 43 ● CR= 26 % + PR= 12% = 37% ● Better survival for responders, p<.05 ● Active agent

GOG 34 Phase III, surgery + radiotherapy +- Doxorubicin in stage IC, II and IIIA EC ● Doxo 60 mg/m2 q 3 /52 up to 500 mg ● No G 3 – 4 cardio toxicity ● Survival 60 vs 66%, p= NS ● “Unable to determine effect” ● 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 ● Doxo CDDP 50 mg/m2 q 3/52 ● N= 281 ● 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

● Adverse events were more common with AP ● At 24 mo: p<0.01: – 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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