Transcript Diapositiva 1

ASCO Update: Italy
Thomas J. Herzog, MD
Professor & Director, Division
Gynecologic Oncology
Columbia University
June, 2010
What’s New in Gyn Oncology?

Ovarian Cancer
– Screening update
– GOG 218
– Developmental therapeutics
 New chemotherapy
 New biologics
ASCO 2010: Lu (#5003)



Triage algorithm
based on age and
serial changes in
CA125 among healthy
women
Single arm,
prospective
multicenter trial
N=3252, 8 years

Patients:
–
–
–

ROCA = Risk of Ovarian Cancer Algorithm
Menopausal
Age: 50-74, with at
least 1 ovary
No significant family
history of breast of
ovarian cancer
Testing:
–
–
Annual CA125
ROCA
ASCO 2010: Lu (#5003)
ROCA (n=3238)
6.8% annual referral
0.9% annual referral
Low-Risk Intermediate-Risk High-Risk
Annual CA125
Repeat CA125
in 3 mos
ROCA = Risk of Ovarian Cancer Algorithm
TVS and Gyn Onc
Referral
Surgery?
ASCO 2010: Lu (#5003)
ROCA (n=3238)
Cumulatively 85 women (2.6%) were referred 0.9% annual referral
for TVS
and saw a Gyn Oncologist
• 8 women went to surgery (9.4% of referrals)
• 3 invasive cancers (Stage IC (2), Stage IIB)
• 2 LMP
• 3 benign
TVS and Gyn Onc
• PPV: 37.5% (95% CI: 8.5-75.5%)
Referral
• Specificity of ROCA: 99.7% (99.5-99.5%)
• All 3 cancers had serial CA125 which were
Surgery?
stable before rising (incident cases)
High-Risk
ROCA studies are very consistent

UKCTOCS
–
–
–

Sensitivity: 89.4%
Specificity: 99.8
Positive predictive value (PPV): 35.1
US, Lu
–
–
Specificity: 99.8%
PPV 37.5%
ROCA = Risk of Ovarian Cancer Algorithm
Bevacizumab: GOG-0218- Schema
Arm
Carboplatin (C) AUC 6
Front-line:
Epithelial OV, PP
or FT cancer
• Stage III optimal
(macroscopic)
• Stage III
suboptimal
• Stage IV
n=1800 (planned)
Paclitaxel (P) 175 mg/m2
R
A
N
D
O
M
I
Z
E
I
Placebo
Carboplatin (C) AUC 6
1:1:1
Paclitaxel (P) 175 mg/m2
BEV 15 mg/kg
II
Placebo
Carboplatin (C) AUC 6
Stratification variables:
• GOG performance status
(PS)
• Stage/debulking status
Paclitaxel (P) 175 mg/m2
III
BEV 15 mg/kg
Cytotoxic
(6 cycles)
Maintenance
(16 cycles)
15 months
GOG-0218: Statistical Design for
Primary Endpoint

Planned sample size of 1800
–
Based on 90% power to detect PFS hazard ratio (HR)
0.77


Median PFS shift: 14.0 months (historical)  18.2 months
Primary analyses- Compare investigatorassessed PFS for each BEV arm vs control

Protocol defined: RECIST, global clinical deterioration, or CA125 (Gynecologic Cancer Intergroup criteria1)

Per regulatory mandate: RECIST or global clinical
deterioration, censoring for CA-125 (Gynecologic Cancer
Intergroup criteria)
1. Rustin et al. J Natl Cancer Inst 2004
2. Burger RA ASCO 2010 LBA1
8
GOG-0218: Study Conduct

1873 patients enrolled from 336 sites in four countries
(US, Canada, South Korea, Japan), October 2005–June 2009

Key protocol amendments
–
Inclusion of optimally debulked (macroscopic residual disease) patients
(August 2007; 478 patients enrolled)
–
Primary endpoint changed to PFS (October 2008; 1298 patients enrolled)

Final data analysis triggered by pre-specified number of events in the
control arm (data locked February 5, 2010)

Analyses

–
Efficacy population: n=1873 (intent to treat, all randomized patients)
–
Safety population: n=1816 (all randomized patients who received any study
treatment during cycle 2 or later)
Median follow-up: 17.4 months (range 0.0–50.7 months)
Burger RA, ASCO 2010 LBA1
GOG-0218: Baseline Surgical–
Pathologic Characteristics
Arm I
CP
(n=625)
Arm II
CP + BEV
(n=625)
Arm III
CP + BEV  BEV
(n=623)
III optimal (macroscopic)
218 (35)
205 (33)
216 (35)
III suboptimal
254 (41)
256 (41)
242 (39)
IV
153 (25)
164 (26)
165 (27)
543 (87)
523 (84)
525 (84)
Endometrioid
20 (3)
15 (2)
25 (4)
Clear cell
11 (2)
23 (4)
18 (3)
Mucinous
8 (1)
Characteristic, n (%)
Stage/residual size
Histology
Serous
5 (<1)
8 (1)
Tumor grade
3a
412 (66)
435 (70)
430 (69)
2
94 (15)
77 (12)
92 (15)
1
33 (5)
28 (4)
16 (3)
Not specified/pending
86 (14)
85 (14)
85 (14)
Percentages may not total 100% due to rounding
aGr. 3 includes all clear cell
GOG-0218: Patient Disposition
Characteristic
Median (range) number BEV/placebo cycles
Patients on study treatment at time of data
lock (Feb 5, 2010), n (%)
Arm I
CP
(n=625)
Arm II
CP + BEV
(n=625)
Arm III
CP + BEV  BEV
(n=623)
11 (0–22a)
12 (0–22a)
14 (0–21)
86 (14)
82 (13)
117 (19)
100 (16)
104 (17)
148 (24)
299 (48)
264 (42)
164 (26)
Adverse events
69 (11)
86 (14)
94 (15)
Cycles 1–6
57 (9)
73 (12)
59 (9)
Cycle ≥7
12 (2)
13 (2)
35 (6)
8 (1)
7 (1)
13 (2)
Patient refusal
44 (7)
55 (9)
50 (8)
Other
19 (3)
27 (4)
37 (6)
Completed regimen, n (%)
Discontinued study treatment, n (%)
Disease progression
Deaths
Burger RA, ASCO 2010 LBA1
GOG-0218: Adverse Events
Onset between cycle 2 and 30 days after date of last treatment
Adverse event (grade when limited), n (%)
GI eventsa (grade ≥2)
Hypertension (grade ≥3)
Proteinuria (grade ≥3)
Pain (grade ≥3)
Neutropenia (grade ≥4)
Arm I
CP
(n=601)
Arm II
CP + BEV
(n=607)
Arm III
CP + BEV  BEV
(n=608)
7 (1.2)
17 (2.8)
16 (2.6)
10 (1.7)b
36 (5.9)b
63 (10.4)b
4 (0.7)
4 (0.7)
55 (9.2)b
73 (12.0)b
10 (1.6)
83 (13.7)b
347 (57.7)
384 (63.3)
385 (63.3)
Febrile neutropenia
21 (3.5)
30 (4.9)
26 (4.3)
Venous thromboembolic event
35 (5.8)
32 (5.3)
41 (6.7)
Arterial thromboembolic event
5 (0.8)
4 (0.7)
4 (0.7)
CNS bleeding
0
0
2 (0.3)
Non-CNS bleeding (grade ≥3)
5 (0.8)
8 (1.3)
13 (2.1)
RPLS
0
1 (0.2)
1 (0.2)
Burger RA, ASCO 2010 LBA1
GOG-0218: Select Adverse Events by
Treatment Arm
Arm I
CP
Select adverse events, n
(grade when limited)
Arm II
CP + BEV
Arm III
CP + BEV  BEV
Patients, n
(n=601)
(n=483)
(n=607)
(n=457)
(n=608)
(n=464)
Cycles, n
2906
4059
2911
4204
2891
4677
Treatment phasea
Cytotoxic Maintenance( Cytotoxic Maintenance Cytotoxic Maintenance
(cycles 2–6) cycles ≥7) (cycles 2–6) (cycles ≥7) (cycles 2–6) (cycles ≥7)
GI eventsb (grade ≥2)
6
1
16
1
15
1
Hypertension (grade ≥3)
3
7
24
12
25
38
Proteinuria (grade ≥3)
2
2
4
0
0
10
28
23
42
31
46
37
345
2
382
2
385
0
Febrile neutropenia
21
0
30
0
26
0
Venous thromboembolic event
26
9
27
5
27
14
Arterial thromboembolic event
4
1
1
3
3
1
CNS bleeding
0
0
0
0
0
2
Non-CNS bleeding (grade ≥3)
3
2
8
0
10
3
RPLS
0
0
1
0
0
1
Pain (grade ≥3)
Neutropenia (grade ≥4)
Burger RA, ASCO 2010 LBA1
GOG-0218: Investigator-Assessed PFS
Proportion surviving progression free
1.0
0.9
Patients with event, n (%)
0.8
Median PFS, months
0.7
Arm I
CP
(n=625)
Arm II
CP + BEV
(n=625)
Arm III
CP + BEV  BEV
(n=623)
423
(67.7)
418
(66.9)
360
(57.8)
10.3
11.2
14.1
0.908
(0.759–1.040)
0.717
(0.625–0.824)
0.080*
<0.0001*
Stratified analysis HR
(95% CI)
0.6
One-sided p-value (log rank)
0.5
0.4
0.3
0.2
CP (Arm I)
+ BEV (Arm II)
0.1
+ BEV → BEV maintenance (Arm III)
0
0
12
24
Months since randomization
36
*p-value boundary = 0.0116
GOG-0218: Subgroup Analyses of PFS
CP + BEV  BEV (Arm III) vs CP (Arm I)
Hazard ratio
Stage 3 optimal (n=434)
0.618
Stage 3 suboptimal (n=496)
0.763
Stage 4 (n=318)
0.698
PS 0 (n=616)
0.710
PS 1/2 (n=632)
0.690
Age <60 years (n=629)
0.680
Age 60–69 years (n=409)
0.763
Age 70 years (n=210)
0.678
Experimental arm
(CP + BEV  BEV;
Arm III) better
0.33
Control arm
(CP; Arm I) better
0.5 0.67
1.0
1.5 2.0
Treatment hazard ratio
3.0
GOG-0218: Mean Patient-Reported
TOI Score During Chemotherapy
Mean TOI score
112
100
90
80
70
60
50
40
30
20
10
0
CP (Arm I)
Randomization
CP + BEV  BEV (Arm III)
Pre-cycle 4
Pre-cycle 7
TOI = Trial Outcome Index of the Functional Assessment of Cancer
Therapy-Ovary (FACT-O TOI): FACT-G [Physical Well-Being (7 items),
Functional Well-Being (7 items)] &Ov Cancer Subscale (12 item)
GOG-0218: Overall Survival Analysis
At time of final PFS analysis (January 2010)
Proportion surviving
Patients with events, n (%)
1.0
Median OS, months
0.9
Stratified analysis
HR (95% CI)
Arm I
CP
(n=625)
Arm II
CP + BEV
(n=625)
Arm III
CP + BEV 
BEV
(n=623)
156 (25.0)
150 (24.0)
138 (22.2)
39.3
38.7
39.7
One-sided p-value
0.8
1.036
0.915
(0.827–1.297) (0.727–1.152)
0.361
0.252
0.7
0.6
0.5
0.4
0.3
0.2
CP (Arm I)
+ BEV (Arm II)
0.1
+ BEV → BEV maintenance (Arm III)
0
0
12
24
36
Months since randomization
48
Burger RA, ASCO 2010 LBA1
GOG-0218: Conclusions

GOG-0218 met the primary objective in the front-line treatment of
advanced ovarian (epithelial OV, PP and FT) cancer
–
PFS with CP + BEV (Arm II) not statistically superior to CP (Arm I) alone
–
PFS with CP + BEV  BEV maintenance (Arm III) statistically superior to
CP (Arm I) alone

Interpretation of survival analysis limited

Treatment regimen was generally well tolerated; adverse events (including
GI perforation) similar to previous BEV studies

No decrement in quality of life during chemotherapy phase

BEV - first molecular targeted and first anti-angiogenic agent to
demonstrate benefit in this population
–
CP + BEV  BEV maintenance can be considered as a standard option
Burger RA, ASCO 2010 LBA1
ICON7: Study Design
Carboplatin
AUC 6*
Paclitaxel 175
mg/m2
Front-line
EOC, PP or
FT cancer
• Stage I-IIA (Gr 3
or CC)
• Stage IIB/C
• Stage III
• Stage IV
n=1520 (planned)
Stratification variables:
• Stage/surgery
• Time since surgery
• GCIG group
**
Carboplatin
AUC 6*
Paclitaxel 175
mg/m2
Bevacizumab 7.5 mg/kg
Primary
endpoints:
PFS
Secondary
endpoints: OS,
RR, safety,
QOL,
costeffectiveness,
translational
No IRC present
12 months
*Might vary based on GCIG group
**Omit cycle 1 bevacizumab if <4 wks from surgery
Key Differences Between
GOG-0218 and ICON7
Trial
GOG-0218
ICON7
Setting/
design
•
•
•
•
Patient
population
• Stage III (suboptimal)
• Stage III (optimal, visual/palpable)
• Stage IV
• Stage I or IIA (grade 3 or
clear cell histology)
• Stages IIB-IV (all)
Additional
endpoint
• OS analysis (formal testing
at time of PFS)
• IRC
• Defined final OS analysis
(end 2012)
• No IRC
Double-blinded, placebo-controlled
Three-arm study
Bev for 15 months
Bev dose: 5 mg/kg/wk
•
•
•
•
Open-label
Two-arm study
Bev for 12 months
Bev dose: 2.5 mg/kg/wk
GOG 213
Platinumsensitive,
recurrent
OC, PP, FTC
Prior bev
allowed
Carboplatin
AUC 5
Paclitaxel 175
mg/m2
Surgical
candidate
?
No
Yes
R
n=660
Surgery
No
Surgery
Stratification
variable:
• Time to recurrence
R
Carboplatin
AUC 5
Paclitaxel 175
mg/m2
Bevacizumab 15 mg/kg to progression
Primary endpoints: OS (secondary
cytoreduction), OS (bevacizumab)
Secondary endpoints: PFS,
hypersensitivity, QOL, translational
No IRC present
ASCO 2010: Developmental
Therapeutics

Phase III updates
–
–
–
–
MITO-2
TCON
OVA-301
CALYPSO


NKTR-102
Folate:
–

Angiogenesis:
–

EC-145
AMG-386
PARP
Phase III Study: MITO-2
Ovarian cancer
- Stage IC-IV
- Age ≤ 75
- PS: 0-2
- Iº Endpoint: PFS
R
A
N
D
O
M
I
Z
E
Paclitaxel 175 mg/m2
Carboplatin AUC 5
Every 3 weeks
Relapse
PLD 30 mg/m2
Carboplatin AUC 5
Every 4 weeks
Opened: 1/2003
Closed: 11/2007
N = 820 (needed 632 events for HR: 0.8, b=0.2)
Pignata, ASCO 2009, LBA5508
Phase III Study: MITO-2
Characteristic
P
Paclitaxel/Carbo
PLD/Carbo
≥ 6 cycles of therapy
86%
80%
ORR (measurable)
N = 290
59%
57%
0.70
CR (non-target only)
N = 182
33%
29%
0.64
Normalization (CA-125
only)
N = 168
83%
86%
0.56
Pignata, ASCO 2009, LBA5508
Phase III Study: MITO-2
Characteristic
Paclitaxel/Carbo
PLD/Carbo
P
Anemia (All Grades)
59%
68%
<0.05
Thrombocytopenia (All Gr)
19%
48%
<0.05
Alopecia
63%
14%
<0.05
PPE (All Grades)
6%
20%
<0.05
PPE (Gr 3-4)
0%
2%
<0.05
Stomatitis
9%
20%
<0.05
Diarrhea
13%
16%
<0.05
Neurotoxicity (All Grades)
47%
15%
<0.05
Pignata, ASCO 2009, LBA5508
MITO-2: PLD/Carbo vs. Pac/Carbo
0.8
Cut-off for analysis: 12/09
Median PFS
Patients
Events
Months (95% CI)
Standard
410
282
16.8 (15.2 - 19.4)
Experimental
410
274
19.0 (16.3 - 24.0)
0.2
0.4
0.6
Hazard Ratio 0.95 (0.81 – 1.13)
Log-rank test p = 0.58
0.0
Probability of progression-free survival
1.0
Progression-free survival
0
6
12
18
24
30
36
42
48
54
60
66
72
Months
Pignata ASCO 2010 LBA5033
Phase III trial of induction
gemcitabine (G) or paclitaxel (T)
plus carboplatin (C) followed by
elective T consolidation in
advanced ovarian cancer (OC):
Final safety and efficacy report TCON trial.
M.G. Teneriello, et al. ASCO 2010LBA 5008
Patient Disposition– TCON
Enrolled
(N = 919)
Patients randomly assigned
(n = 916)
Excluded
(n = 3)
Not meeting inclusion criteria
(NA)
Other
(NA)
Excluded (clerical errors)
Allocated to GC
Received GC
Withdrew
Allocated to TC (n = 414)
Received TC(n = 409)
Withdrew
(n = 5)
(n = 417)
(n = 411)
(n = 6)
Discontinued
(n = 148)
Patient request
(n =
39)
Toxicity
(n = 37)
Physician request
(n = 11)
Death
(n = 8)
>5 week therapy delay
(n = 7)
Progressive disease
(n = 6)
Other
(n = 19)
Unknown
(n = 6)
Discontinued
(n = 165)
Patient request
(n =
58)
Toxicity
(n = 26)
Physician request
(n = 20)
Death
(n = 6)
>5 week therapy delay
(n = 5)
Progressive disease
(n = 5)
Other
(n = 33)
Unknown
(n = 12)
Received CO-T (n = 77)
Received Tcon
Received Tcon
(n = 85)
(n = 183)
Received CO-G
(n = 169)
M.G. Teneriello, et al. ASCO 2010LBA 5008
(n = 78)
Progression-Free Survival
1.0
Survival Probability
0.9
PFS
 GC (N=417)
 TC (N=414)
Patients censored, n (%)
122 (29.3)
134 (32.4)
Median, months (95% CI)
20.0 (17.9, 22.2)
22.2 (19.0, 25.7)
P-value
0.8
0.7
0.199
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
5
10
15 20
25 30
35 40 45
50 55
60 65
70 75 80
Survival Time (months)
M.G. Teneriello, et al. ASCO 2010LBA 5008
Phase 2 Study of NKTR-102 in PlatResistant Ovarian Cancer
Platinum
resistant/
refractory
ovarian
cancer
(N=70)
NKTR-102
145 mg/m2 q14d
NKTR-102
145 mg/m2
q21d
Stage 1
N=20 /
regimen
Stage 2
N=15 /
regimen
Primary Endpoint:
Objective Response
Rate
(RECIST evaluation
every 6 weeks)
Statistical Hypotheses: 2-stage design (with power of 0.85 for a RR of
20% and with alpha of 0.03 for RR of 5%
Stage 1: If ≥ 1 pt responds, then proceed to next stage
Stage 2: An additional 15 are patients enrolled
If ≥ 5 patients respond out of 35 patients (Stage 1 and Stage 2 combined),
the drug has met the efficacy threshold.
Ignace Vergote et al J Clin Oncol 28:7s, 2010 (suppl; abstr 5013)
Objective Response Rates
(Platinum Resistant / Refractory Patients)
NKTR-102
145 mg/m2 q14d
NKTR-102
145 mg/m2 q21d
Confirmed + Unconfirmed
Confirmed
33
8 (24%)
7 (21%)
31
9 (29%)
7 (23%)
Confirmed + Unconfirmed
Confirmed
34
14 (41%)
10 (29%)
34
14 (41%)
13 (38%)
Confirmed
29
11 (38%)
29
11 (38%)
33
17 (52%)
31
14 (45%)
RECIST
N (evaluable)
GCIG
N (evaluable)
CA-125
N (evaluable)
Clinical Benefit (CR+PR+[SD≥3 months])
N (evaluable)
Confirmed RECIST
Ignace Vergote et al J Clin Oncol 28:7s, 2010 (suppl; abstr 5013)
Maximum Decline by RECIST or CA-125
Platinum Resistant / Refractory Patients
q14d and q21d patients combined
20% Increase
(RECIST)
30% Decrease
(RECIST)
q14d and q21d patients combined
50% Increase
(CA125)
50% Decrease
(CA125)
Ignace Vergote et al J Clin Oncol 28:7s, 2010 (suppl; abstr 5013)
NKTR-102 Safety Profile
Most Common* Drugrelated Grade 3 and 4 AEs
*>5% overall
NKTR-102
145 mg/m2 q14d
(N = 36)
NKTR-102
145 mg/m2 q21d
(N = 35)
Grade 3
Grade 4
Grade 3
Grade 4
Diarrhea
25%
0%
14%
0%
Dehydration
22%
0%
6%
0%
Hypokalemia
17%
3%
9%
0%
Fatigue
6%
0%
14%
0%
Nausea
14%
0%
3%
0%
Vomiting
11%
0%
3%
0%
Abdominal pain
6%
0%
6%
0%
Hyponatremia
8%
0%
3%
0%
Neutropenia
6%
0%
6%
3%
Two NKTR-102 related deaths:
q14d: acute renal failure
q21d: neutropenic sepsis
Utilizing the Folate
Receptor: EC145


Folate-Vinca
conjugate
Relevant for imaging
targeting and
therapy
Reddy JA, et al. Cancer Res. 2007;67:4434-4442.
EC145: Novel Folate Receptor
Targeted Therapeutic


Randomized Phase II, Platinum-resistant ovarian
No more than 2 priors
–

PLD 50 q 4wk vs. PLD 50 mg/m2 IBW q 28 days + EC145 2.5 mg weeks 1
& 3 (cycle: 28 days)
Toxicity similar in both arms: total AEs, SAEs, TETs
Arm
PFS
HR
P
PLD
11.7 wks
-
-
PLD+EC145
24.0 wks
0.497
0.014
Naumann W, et al. ASCO 2010. Abstract LBA5012b.
EC145 Survival Outcomes
Naumann W, et al. ASCO 2010. Abstract LBA5012b.
J Clin Oncol 28:7s, 2010 (suppl; abstr 5000)
J Clin Oncol 28:7s, 2010 (suppl; abstr 5000)
Poly (ADP-Ribose) Polymerase (PARP)
If PARP is inhibited, SSB repair prevented, leading to increased double
strand DNA breaks
PARP inhibitors in clinical trials
Agent
Company
Strategy
Administration
AG014699
Pfizer
Combination
KU59436
AstraZenecaKudos
Single
Oral
ABT-888
Abbott
Single
Oral
BSI-201
BiPar
Single
IV
IV
Combinations
INO-1001
InotekCombination
Roche/Genente
ch
IV
MK
Merck
Single agent
combination
Oral
GPI 21016
MGI Pharma
Combination
Oral
Adapted Ratnam K, Low JA Clin Cancer Res 2007;13: 1383-1388
Response to chemotherapy after PARP
inhibitor - Olaparib
Previous chemotherapies
3 lines
Platinum/taxane resistance
>60%
Median time from start olaparib to chemotherapy
8.7 months
Patients treated with chemotherapy post olaparib
23
RECIST/GCIC ORR with platinum/taxane reinduction
54%
ONLY PTS RECEIVING PLATINUM OR TAXANE RESPONDED
AGAIN
Ang J et al ASCO 2010 Abstract 5041
What is BRCAness?
Molecular Definition:
• BRCA1/2 deleterious mutation or somatic mutation
• Epigenetic silencing BRCA1/2 (5-31%)
• FANCF methylation (~20%) or LoF of other HR genes
• EMSY amplification
• p53 mutation
• c-myc amplification
• Genomic instability
Turner, Tutt, Ashworth NatRevCancer 2004
Weberpals, Clark-Knowles, Vanderhyden JCO 2008
Tan et al, JCO 2008
What is BRCAness?
Phenotypic Definition:
• High ORR rates to platinum-based treatments
• Long progression free intervals between treatments
• Improved OS
• Predominantly serous histology
• Homologous recombination defect
Turner, Tutt, Ashworth NatRevCancer 2004
Weberpals, Clark-Knowles, Vanderhyden JCO 2008
Tan et al, JCO 2008
Objective Response Rate (ORR)
Actual BRCA Mutation Status
Evaluable for RECIST Response
BRCA
Non-BRCA
ORR %
(x/n)
95%
confidence
interval* (%)
ORR %
(x/n)
95%
confidence
interval (%)
Ovarian
(Serous)
41%
(7/17)
21.6, 64.0
24%
(11/46)
13.9, 37.9
Breast
0
(0/8)
0, 32.4
0
(0/15)
0, 20.4
(Triple Neg)
Gelmon K et al J Clin Oncol 28:7s, 2010 (suppl; abstr 3002)
First in Human: PARP Inhibitor MK-4827
in Advanced Cancer Patients with Antitumor Activity in BRCA-Deficient &
Sporadic Ovarian Cancers





MK4827 PO q day
Ovarian (2 BRCA1, 1 BRCA2) = 26 of 56
enrolled patients
MTD = 300mg QD continuously
Thrombocytopenia was dose limiting
7 responders by GCIC criteria (27%) (3 by
RECIST, seen at the highest doses)
Sandhu SK et al J Clin Oncol 28:7s, 2010 (suppl; abstr 3001)
Conclusions:
Gynecologic Cancers ASCO 2010



Most provocative data was from GOG 218 with
front-line Bevacizumab positive trial
Maturation of GOG 218 and ICON-7 data
needed to better understand role of
Bevacizumab in front line therapy
Multiple interesting novel agents including:
–
–

EC 145
AMG 386
PARP inhibitors of significant interest
–
Need to define target population
Grazie!