Sessione platinum series
Best Papers ormonoterapia
G Cartenì
G. Cartenì
Direttore U.O.S.C. di Oncologia Medica A.O.R.N.
A. Cardarelli Napoli
1
Enzalutamide
2
Enzalutamide: PREVAIL‐ Studio di fase III
X
Patients with visceral disease were allowed.
Beer TM, et al. J Clin Oncol 32, 2014 (suppl 4; abstr LBA1^)
3
Enzalutamide: PREVAIL‐ Dati al basale
Beer TM, et al. J Clin Oncol 32, 2014 (suppl 4; abstr LBA1^)
4
Enzalutamide: PREVAIL‐ Overall Survival
32m
30m
X
Patients enrolled for the study generally had a good prognosis.
X
Overall Survival: Enzalutamide Reduced the Risk of Death by 29%
Overall Survival: Enzalutamide Reduced the Risk of Death by 29%.
Beer TM, et al. J Clin Oncol 32, 2014 (suppl 4; abstr LBA1^)
5
Enzalutamide: PREVAIL‐ PFS radiologica
30% of patients in the placebo group progressed at the first assessment. Beer TM, et al. J Clin Oncol 32, 2014 (suppl 4; abstr LBA1^)
6
Enzalutamide: PREVAIL‐ OS nei sottogruppi
Non significativo
X
7
Vantaggio su pazienti con prognosi migliore
Beer TM, et al. J Clin Oncol 32, 2014 (suppl 4; abstr LBA1^)
Enzalutamide: PREVAIL‐ Safety
8
Beer TM, et al. J Clin Oncol 32, 2014 (suppl 4; abstr LBA1^)
PREVAIL Study of Enzalutamide in mCRPC: Conclusions
in mCRPC: Conclusions
•
Treatment with enzalutamide significantly:
–
Reduced risk of death
Reduced risk of death
–
Delayed metastatic progression
–
•
Achieved clinically meaningful response in soft‐
tissue disease
tissue disease
–
Delayed time to cytotoxic chemotherapy
–
Delayed deterioration in quality of life
Enzalutamide well tolerated over prolonged treatment
Beer T, et al. ASCO GU 2014. Abstract 1.
9
Abiraterone
1
Abiraterone: COU‐AA‐302 ‐
b ate o e COU
30
Design
X
Phase 3 multicenter, randomized, double
Phase
3 multicenter, randomized, double‐blind,
blind, placebo
placebo‐controlled
controlled study conducted at study conducted at
151 sites in 12 countries; USA, Europe, Australia, Canada
X
Study permitted patients with ECOG performance status of O or 1; this was stratified b t
between study arms
t d
X
All subjects had previous antiandrogen therapy followed by documented PSA or radiographic progression after discontinuing antiandrogen therapy
Ryan CJ, et al. N Engl J Med 2013;368:138‐48.
1
Abiraterone: COU‐AA‐302 –
Inclusion criteria
l i
i i
Inclusion Criteria for mCRPC
Inclusion Criteria for mCRPC X
Previous anti‐androgen therapy and progression after withdrawal
X
ECOG performance status 0 or 1
ECOG performance status 0 or 1
X
Medical or surgical castration with testosterone < 50 ng/dL
Exclusion Criteria:
X
Prior cytotoxic chemotherapy or biologic therapy for CRPC
X
Prior ketoconazole for prostate cancer
X
Known brain metastasis or visceral organ metastasis
X
Use of opiate analgesics for cancer‐related pain, including codeine and dextropropoxyphene, currently or anytime within 4 weeks of Cycle 1 Day 1
Ryan CJ, et al. N Engl J Med 2013;368:138‐48.
1
Abiraterone: COU‐AA‐302 – Dati al Basale
a.
a.
Patients with BPI‐SF 2 or 3 are not eligible for opioids therapies. For study eligibility, a score of 0‐1 on BPI‐SF Question #3 (worst pain in last 24 hours) will be considered asymptomatic, and a score of 2‐3 will be considered mildly symptomatic.
Consider that In the TAX 327 study :
Ab t 45% f ti t h d i
About 45% of patients had pain, and d
about 40% had measurable soft‐tissue lesions.
a.
Ryan CJ, et al. N Engl J Med 2013;368:138‐48.
1
1
12/15/14
Abiraterone: COU‐AA‐302 – updated analysis results – Overall Survival
1
Abiraterone: COU‐AA‐302 – PFS radiologica
Ryan CJ, et al. N Engl J Med 2013;368:138‐48.
1
Abiraterone: COU‐AA‐302 – Safety
Ryan CJ, et al. N Engl J Med 2013;368:138‐48.
1
O
S
•
r
a
g
g
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t
a
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s
C id
Considerazioni i i
Phase III: Orteronel (TAK‐
700)/Prednisone vs Pl b /P d i
Placebo/Prednisone in mCRPC
i
CRPC
Patients with mCRPC and progression on docetaxel, PSA ≥ 2 ng/mL
(N = 1099)
Orteronel (TAK
Orteronel
(TAK‐700)
700) 400 mg BID +
400 mg BID +
Prednisone 5 mg BID
(n = 734)
Placebo +
Prednisone 5 mg BID
( = 36
(n
365))
ƒ
Primary endpoint: OS
y
p
ƒ
Secondary endpoints: radiographic PFS, PSA response, pain response
Dreicer R, et al. ASCO GU 2014. Abstract 7.
1
Orteronel/Prednisone vs Placebo/ Prednisone in mCRPC: OS
Prednisone in mCRPC: OS
Probability of Pts SSurviving
100
80
60
ƒ
40
Median OS
–
–
20
–
–
0
0
3
Orteronel + Prednisone
Orteronel: 17.0 mos
Orteronel:
17 0 mos
Placebo: 15.2 mos
HR: 0.886 (95% CI: 0.739‐1.062; P = .18976)
Events: 182 with orteronel vs 182 without
h
l
h
6
9
12 15
18
Mos to Death
Mos to Death
Pts at Risk, n
Orteronel +
448 316 217
prednisone 734 665 574
Prednisone 365 336 285
223 151 104
Median follow‐up time: 10.7 mos (range: 0.2‐29.5)
Dreicer R, et al. ASCO GU 2014. Abstract 7.
2
142
59
Prednisone
21
24
27
30
76
33
32
13
1
1
0
0
Prob
bability of Pts Survivving With
hout Diseasse Progression
Orteronel/Prednisone vs Placebo/
Prednisone in mCRPC: Radiographic PFS
100
ƒ
Median PFS
–
80
–
60
–
–
Orteronel: 8.3 mos
Placebo: 5.7 mos
HR: 0.76 (95% CI: 0.653‐0.885; P = .00038)
Events: 262 with orteronel vs 466 without
Events: 262 with orteronel vs 466 without
40
Orteronel + Prednisone
20
Prednisone
0
0
Pts at Risk, n
Orteronel +
Prednisone 734
Prednisone 365
3
6
9
12
15
18
21
Mos to Radiographic PD or Death
Mos to Radiographic PD or Death
553
264
334
138
212
75
130
44
78
29
39
16
17
9
24
27
1
1
0
0
112 (15%) and 74 (20%) pts in the orteronel plus prednisone and prednisone groups, respectively, discontinued before radiographic progression.
Dreicer R, et al. ASCO GU 2014. Abstract 7.
2
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12/15/14
P
r
i
m
a
r
y
•
e
n
d
p
o
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t
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2
O
SDreicer R, et al. ASCO GU 2014. Abstract 7.
Orteronel/Prednisone vs Placebo/
Prednisone in mCRPC: Conclusions
Prednisone in mCRPC: Conclusions
Abstract 21 Response to androgen signaling (AS)‐directed therapy after t t
treatment with abiraterone acetate t ith bi t
t t
(AA) in patients (pts) with metastatic castration‐resistant prostate cancer p
(mCRPC): Post hoc analysis of study COU‐AA‐302. •
Matthew R. Smith et al. 88 pazienti arruolati nello studio COU‐AA‐302 e trattati con abiraterone (pazienti chemo‐
naïve) che hanno ricevuto enzalutamide (33 pazienti) o nuovamente abiraterone (55
pazienti) o nuovamente abiraterone (55 pazienti) dopo l’uscita dallo studio. 2
Abstract 240 Enzalutamide after abiraterone in patients with metastatic castrate‐resistant prostate cancer (mCRPC). Gurprataap Singh Sandhu et al. 23 pazienti Una riduzione del PSA ≥50% è stata descritta solo in 4 pazienti (17%) mentre la mediana di PFS biochimica era di 86 giorni. A 6 mesi, solo 2 pazienti presentavano una stabilità strumentale di malattia. 2
Abstract 159 Clinical activity of enzalutamide against metastatic castration‐resistant prostate cancer (mCRPC) in patients who have progressed on abiraterone acetate: The Princess Margaret experience. Francisco Emilio Vera‐Badillo et al. Sono stati arruolati in totale 26 pazienti, la Sono
stati arruolati in totale 26 pazienti, la
durata mediana del trattamento è stata di 4,4 mesi (range 1,3‐ 9,3 mesi) con interruzione dovuta a: • progressione clinica o biochimica (92%) • comparsa di fatigue di grado ≥3‐4 in 2 pazienti (8%). L’analisi dei dati ha rilevato che in 7 (27%) dei pazienti trattati si è ottenuta una riduzione del PSA ≥50% e in ulteriori 7 (27%) una
del PSA ≥50% e in ulteriori 7 (27%) una riduzione ≥30%. La PFS è stata di 4,9 mesi, in linea con quella riscontrata negli altri studi e migliore rispetto
riscontrata negli altri studi e migliore rispetto a quella ottenuta con abiraterone dopo enzalutamide. 2
Abstract 70 A prognostic score for patients with metastatic castration‐resistant prostate cancer treated with abiraterone p
py
acetate post chemotherapy. •
Arnoud J. Templeton et al. dati clinici e laboratoristici di 185 pazienti seguiti al Royal Marsden di Londra e successivamente valutati attraverso l’analisi di regressione univariata di Cox.
regressione univariata di Cox.
Il modello è stato validato utilizzando come riferimento il trial registrativo COU‐AA 301 2
Stretta correlazione tra sopravvivenza e NLR: i pazienti con NLR≥5 al basale e che mostravano una riduzione del valore ≤5 entro
mostravano una riduzione del valore ≤5 entro le prime 4 settimane di trattamento hanno ottenuto una mOS di 15 mesi, mentre quelli che mantenevano un valore di NLR ≥5 hanno h
t
l
di NLR ≥5 h
ottenuto una mOS di appena 7,6 mesi (HR 0,48; IC 95% 0,25‐0,93; p=0,029). 2
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RESISTANCE
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Second Outline Level
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Third Outline Level
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− Fifth Outline Level
Fifth Outline Level
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− Seventh Outline Level
− Eighth Outline Level
Eighth Outline Level
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2
AR -
AR +
Secondo livello
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Terzo livello
P. Nelson, ASCO GU - 2014
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Natural
history
and
treatment
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progression
i off prostate cancer
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Second Outline Level
−
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Third Outline Level
z Fourth Outline Level
− Fifth Outline Level
Fifth Outline Level
− Sixth Outline Level
− Seventh Outline Level
− Eighth Outline Level
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Ninth Outline LevelFare clic per
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3
Death
Secondo livello
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Terzo livello
Nguyen PL, et al. 2007; 110:1417-1428 - Adapted
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Natural
history
and
treatment
Click to edit the outline text format
progression
i off prostate cancer
z
Second Outline Level
−
•
Third Outline Level
z Fourth Outline Level
− Fifth Outline Level
Fifth Outline Level
− Sixth Outline Level
− Seventh Outline Level
− Eighth Outline Level
Eighth Outline Level
Ninth Outline LevelFare clic per
Ninth Outline LevelFare clic per modificare stili del testo dello schema
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3
Death
Secondo livello
•
Terzo livello
Nguyen PL, et al. 2007; 110:1417-1428 - Adapted