1. Joan L. Walker, M.D. Stephenson Cancer Center University of Oklahoma
A phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube and primary peritoneal carcinoma NCI-supplied agent(s): bevacizumab (NSC #704865, IND #7921) NCT a GOG/NRG Trial
Joan L. Walker, M.D. Stephenson Cancer Center University of Oklahoma

2. Co-Authors
Mark F Brady; Paul A DiSilvestro; Keiichi Fujiwara; David Alberts,Wenxin Zheng; Krishnansu Tewari; David E Cohn; Matthew Powell; Linda van Le; Stephen Rubin; ,Susan A Davidson ; Heidi J Gray; Steven Waggoner; Tashanna Myers; Carol Aghajanian; Angeles Alvarez Secord; Robert S Mannel

3. Verbal Disclosure
Dr. Walker has not personally received funding for this trial
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517),
NRG Oncology Operations U10CA
NRG Oncology SDMC U10SDMC grant
NCORP grant UG1CA189867

4. GOG #172 Armstrong et.al. N Engl J Med 2006;354:34-43
Paclitaxel 135 mg/m2/24h
Cisplatin 75 mg/m2
q 21 days x 6 R A N D O M I Z E
Ovarian cancer
Optimal (<1cm)
Stage III
Stratify:
Gross residual
Planned 2nd look
Paclitaxel 135 mg/m2/24h
Cisplatin 100 mg/m2 IP D2
Paclitaxel 60 mg/m2 IP D8
q 21 days x 6

5. IP Chemotherapy Survival in Optimally Resected Stage III Ovarian Cancer
Clinical Trial N
per arm
Events per arm
IP Arm
IV Arm
IP OS
Median mos
IV OS HR
P-value
logrank
GOG 104
(Alberts, 1996 NEJM)
IV 279
IP 267
IV 174
IP 147
IP cisplatin 100 mg/m2
IV cyclophosphamide 600 mg/m2
IV cisplatin (100 mg/m2)
IV cyclophosphamide (600 mg/m2) 49 41
0.76
95% CI ;
0.02
GOG 114
(Markman, 2001)
IV 227
IP 235
IV124
IP 109
IV carboplatin AUC 9 X 2 cycles
IV paclitaxel 135 mg/m2
IP cisplatin 75 mg/m2
IV cisplatin 75 mg/m2
63.2
52.2
0.81
90% CI 0.65;1.0
0.05
GOG 172
(Armstrong, 2006)
IV 210
IP 205
IV 127
IP 101
IP paclitaxel 60 mg/m2 Day 8 65
0.75
95% CI 0.58;0.97
0.03
To date, there have been three large randomized clinical trials conducted by the GOG which demonstrate a survival advantage for patients treated with IP chemotherapy

6. Patients with No Residual Disease- IP cisp
Months
When stratified by individual study, patients receiving IP chemotherapy on GOG 172 with no residual had the best out come measures with PFS of 60 months and OS of 128 months.

7. GOG 252
I WOULD INCLUDE ALL THIS INFO BELOW AS YOU ARE SPEAKING ABOUT THIS SLIDE AND ANIMATE
Dose reduction cisplatin(100 down to 75 mg/m2)
Infusion time reduction 135 mg/m2 paclitaxel(3 hr instead of 24h)
All outpatient therapy
Bevacizumab 15 mg/m2 for all
Comparison arm dose dense paclitaxel with carbo IV- winner of GOG 262 (if no bevacizumab) and JGOG

8. Differences in Dosing in GOG 252
compared to GOG 172
Dose reduction cisplatin(100 down to 75 mg/m2)
Infusion time reduction 135 mg/m2 paclitaxel
(3 hr instead of 24h)
All outpatient therapy
Bevacizumab 15 mg/m2 for all
Comparison arm dose dense paclitaxel with carbo IV- winner of GOG 262 (if no bevacizumab) and JGOG

9. Eligibility
Stage II-III Epithelial Carcinoma: Ovary, Fallopian Tube, Peritoneal (88% participants)
Resected to optimal: less than or equal to 1 cm
Exploratory: suboptimal (7%) and Stage IV (5%)

10. Accrual 1560 participants from July 2009-Nov 2011
Median age - 58 years
White 90%; Black 3%; Hispanic 3%
Stage III- 84%
Grade 3 Serous – 72%
No residual disease – 57%

11. GOG 252 1560 participants enrolled from 213 clinics in the US
Randomly assigned treatment
521 assigned to (IV-Carboplatin)
Paclitaxel 80 mg/m2 IV
on days 1, 8 and 15
+ Carboplatin AUC 6 IV on day 1
every 21 days for cycles 1-6
+ Bevacizumab 15 mg/kg IV
every 21 days for cycles 2-22
518 assigned to (IP-Carboplatin)
Paclitaxel 80 mg/m2 IV
on days 1, 8 and 15
+ Carboplatin AUC 6 IP on day 1
every 21 days for cycles 1-6
+ Bevacizumab 15 mg/kg IV
every 21 days for cycles 2-22
521 assigned to (IP-Cisplatin)
Paclitaxel 135 mg/m2 IV on day 1
+ Cisplatin 75 mg/m2 IP on day 2
+ Paclitaxel 60 mg/m2 IV on day 8
every 21 days for cycles 1-6
+ Bevacizumab 15 mg/kg IV
every 21 days for cycles 2-22
511 Initiated study treatment
and evaluated for adverse events
10 did not initiate treatment
510 Initiated study treatment
and evaluated for adverse events
8 did not initiate treatment
508 Initiated study treatment
and evaluated for adverse events.
13 did not initiate treatment
521 Evaluated for PFS and OS
135 Alive and progression-free
255 Alive at last contact
518 Evaluated for PFS and OS
147 Alive and progression-free
262 alive at last contact
521 Evaluated for PFS and OS
139 alive and progression-free
249 alive at last contact

12. Toxicity
90% of participants on all arms experienced grade 3 or worse toxicity
G3 GI fistula/necrosis/leak – Arm 1 = 5.3%
HTN G3- Arm 3 = 20.5% (11.9%; 13.8%)
Neuropathy – Arm 1- G2 or worse = 30%
G3 Nausea/vomiting – Arm 3 =11.2%

13. Progression-Free Survival (PFS)
All Patients by Randomized Treatment.

14. Progression-Free Survival (PFS)
Patients with Stage 2 or 3 and 1 cm or less

15. Progression-Free Survival by Treatment Group
Stage 3 <1 cm

16. Progression-Free Survival by Treatment Group
Stage 2 or 3 with No Gross Residual Disease

17. All Patients by Randomized Treatment
Overall Survival
All Patients by Randomized Treatment

18. Patients with Stage 2 or 3 Residual < 1 cm
Overall Survival
Patients with Stage 2 or 3 Residual < 1 cm

19. Stage 2 or 3 with No Gross Residual Disease
Overall Survival
Stage 2 or 3 with No Gross Residual Disease