Andreia Freire Coelho Medical Oncology Resident, Hospital S. João, Oporto - Portugal

Preceptorship on Prostate Cancer16th-17th October, Lugano - Switzerland

A (Re)challenging Case

Identification:

Male

66 years-old

Retired factory worker

ECOG PS 1

Clinical background:Atrial fibrillationDiabetes mellitus type 2Arterial hypertensionHabits:- Tobacco: ex-smoker- Alcohol: marked ingestion

No allergies

Usual medication:Sulphonylurea 60 mg, 2/dayLosartan 50 mg + HCTZ 12,5 mg, 1/dayCarvedilol 6.25 mg, 2/dayAcetilsalicilic acid 150 mg, 1/dayTramadol 100 mg, 2/dayMetamizole 575 mg, 1/day

Familiar background:No history of cancer cases

May – September 2007:

Hip pain with walking claudication

Bone scan (08.07): diffuse bone metastization

PSA ↑: 801 ng/mL

DRE: enlarged heteregenous prostate, stiff nodules

Prostate biopsy: adenocarcinoma, Gleason 7 (3+4)

TAC-CT (09.07): bone metastasis only

cT4NxM1, stage cIV - mPC

66 years old, ECOG PS 1 (bone pain)

Bone metastasis only

Gleason 7

Baseline:

PSA: 801 ng/mL

LDH: 272 U/L

ALP: 332 UI/L

Hb: 11,4 gr/dL

2

Sep.07

PSA

val

ue

(ng/

mL)

Goserelin 10.8 µg sc, 12/12 weeks

Bone pain resolution

No walking limitation

Dec.08

Moderate-severe bone pain

Marked walking limitation

Bone scan and TAP CT: ↑ bone metastasis

Feb.09

0,2

18,551,5

83,2>100

801,4

59,1

PFS: 18 months

Jan.08

Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Goserelin 10.8 µg sc, 12/12 weeks

Bicalutamide 50 mg po, 1/day

May.09

Met

asti

cca

stra

tio

nre

sist

ant

pro

stat

eca

nce

r…

Dec.07

14,2

Nov.08

ECOG PS 0

Mar.09

ECOG PS 2

3

Docetaxel 75 mg/m2 iv, 21/21 days + Prednisolone 5 mg po, 2/dayEnzalutamide 160

mg/day, 28/28 days

Jun.09 - 1st Treatment

9 cycles, G1 diarrhea

Feb.11 - 1st Rechallenge

11 Cycles, G1 asthenia

Oct.12 – 2nd Rechallenge

7 Cycles, G1 neuropathy

Sep.13 - 3rd Rechallenge,

6 cycles, G2 neuropathy

Jan.14 - Treatment begins

6 cycles, G1 myalgias

Bone pain ↓↓

Minor walking limitation

ECOG PS 1

No bone pain

Minor walking limitation

ECOG PS 1

No bone pain

Minor walking limitation

ECOG PS 1

No bone pain

Minor walking limitation

ECOG PS 1

No bone pain

Minor walking limitation

ECOG PS 1

Zoledronic ac. 4 mg iv, 21/21 days Zoledronic ac. 4 mg iv, 3/3 months

Aug.12 - Bone scan: ↑

bone metastasis

Sep.13 - TC and

Bone scan: ↑ bone

metastasis

Dec.13 - Bone scan: ↑ vsflare of bone metastasis?

Fungal right cornea ulcerby foreign object

An

talg

icR

th, 3

0 G

y, 1

2 f

rP

SA v

alu

e(n

g/m

L)

>100

<0,050,81

13,552,52

4338

70257

386

905

Jun.09 Sep.10 Oct.12 May.13 Sep.13 Jan.14

Metastatic Castration Resistant Prostate Cancer (mCRPC)

Dec.09 Feb.11 Sep.11

7,39

Sep.12 Mar.13 Oct.13 Dec.13

700

32.8

May.14

1,13

Aug.14

Mar.13 - TC and Bone

scan: stable bone

metastasis

3

PFS: 20 months PFS: 19 months PFS: 11 months PFS: 3 months PFS: 8 months

Elder patient

ECOG PS 0-1

2007: mPC (bone metastasis only, Gleason 7)

OS: 7 years

mHSPC

AD (LHRH Ag +/- AA)

PSA ↓ 50%

PFS: 18 months

mCRPC

Docetaxel Rechallenges:

Progresion ≥ 6 months after stopping Docetaxel

1st, 2nd: PSA ↓, stable disease

3rd: PSA ↑ (3 months) - progresion (docetaxelresistance)?

Minor toxicity

Serious infection intercurrence

PFS: 20 » 19 » 11 » 3 months

Enzalutamide

Still good response

PSA ↓ 50%

PFS: 8 months

4

Rechallenge:

- Progresion ≥ 6 months after stopping Docetaxel

- 50% responders

- Posible preditive factors:

. Time from previous cycle to progresion

. Time slope-log PSA

- Benefit on OS?: unclear

- Cabazitaxel

Benefit on OS after Docetaxel treatment

5

Drug sequence may affect response to subsequent therapies

Lack of prospective trials

Decisions driven by clinical and biological parameters and drugs availibility

Discu

sion

Top

ics

Cth with Docetaxel: standard of care in mCRPC

Progresion after 1st line Docetaxel: what’s next?

Cross resistance: AR targeted pathway agents ↔ Taxanes

mCRPC treatment: Which is the best sequencing therapy and when

to switch? We don´t all do the same…

Abiraterone, enzalutamide

- Benefit on OS after Docetaxel treatment

Thank you for your attention