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Relapsed Carcinoma Ovary
Overview
Ovarian cancer management
Relapsed Ca Ovary
Antiangiogenesis in Ca Ovary
PARP Inhibitors in Ca Ovary
Discussion
Jun 2009 Dec 2012-May 2013 Jun 2014-Dec2014 Feb 2016-Jun 2016 Feb 2017-July 2017 August 2017-Nov 2017 Dec 2017-Present Day
Endometriosis
Bleeding PV
TAH+LSO+RS
RO+Omentectomy
Ca Ovary Stage 1A
No Residual
2nd Relapse
Adenocarcinoma
6#PLD+Carboplatin:CR
4th Relapse
18#Weekly NabPaclitaxel+
Bevacizumab: PD
6th progression
3#Gemcitabine+Carboplatin
+ Bevcizumab
ECOG PS:1
ADL:Normal
CA125 Decreasing trend
No Pain/Ascitis
1st Relapse
Adenocarcinoma
6# Paclitaxel+
Carboplatin:CR
5th Progression
4# Topotecan+
Bevacizumab:
PD
Management Timeline a Case
Overall Survival:8 year 6 month
36month 12 month 14 month 8 month 1 month 2 week
3rd Relapse
Adenocarcinoma
6# Paclitaxel+
Carboplatin:CR
Ca Ovary Epidemiology
Ovarian Cancer histology
Ovarian Carcinoma: Clinical Course
Symptoms
Diagnosis
Chemotherapy #1
Staging
Primary cytoreduction
Interval
Cytoreduction
Progression
Chemo #2 Chemo #3+
Supportive
Care
Death
Consolidation/
Maintenance
Cure
Secondary
CytoreductionSecond-Look
Relapsed Carcinoma Ovary
Relapsed Carcinoma Ovary
Management goals
Control Disease
Whom to treat?
MRC OV 05/EORTC 55959
Decision points:Platinum Free Interval
Role of secondary debulking surgery
Controversial
but
Can be tried in
selective cases
How to treat with ?
Raja A.Annals of Oncology 24: 3028–3034, 2013
Platinum-combination chemotherapy
in platinum-sensitive recurrent ovarian cancer
Platinum Sensitive Ca Ovary
Platinum Resistant Ca Ovary
How we treat Relapsed Ca Ovary in 2018
Concepts of Ca ovary
VEGF
Angiogenesis inhibitor in carcinoma ovary
Front-line:
epithelial OV, PP
or FT cancer
 Stage III optimal
(macroscopic)
 Stage III
suboptimal
 Stage IV
N=1,873
• Stratification variables
– GOG performance status
– stage/debulking status
15 months
Paclitaxel (P) 175mg/m2
Carboplatin (C) AUC6
Carboplatin (C) AUC6
Paclitaxel (P) 175mg/m2
Carboplatin (C) AUC6
Paclitaxel (P) 175mg/m2
I
II
III
Arm
1:1:1
Burger RA, et al. Gynecol Oncol. 2013;131:21-6 OV = ovarian; PP = primary peritoneal
AUC: Area Under Curve
GOG: Gynaecologic Oncology Group
R
A
N
D
O
M
I
S
E
Placebo Q3W
Placebo Q3W
Bevacizumab 15mg/kg
Bev 15mg/kg
Bevacizumab in Platinum Sensitive Ca Ovary:
GOG 218 Trial
Burger RA, et al. Gynecol Oncol. 2013;131:21-6.
CP 
Placebo
(n=625)
Bev + CP  Bev
(n=623)
Median PFS (months) 12.0 18.2
HR=0.62 (95% CI, 0.52–0.75) P<0.0001
ITT PFS :Significantly increased PFS with
continued Bevacizumab compared to
standard chemotherapy
GOG 218: Outcomes
CP  Placebo
(n=625)
Bev + CP  Bev
(n=623)
Median OS (months) 40.6 43.8
HR=0.62 (95% CI, 0.75–1.04) P<0.0641
Median OS trending towards benefit in ITT
population
Bevacizumab in Platinum Resistant Ca
Ovary: AURELIA Trial
Randomized Phase III clinical trial in Platinum Resistant Ovarian Cancer
Bevacizumab
10 mg/kg q2w*
+ chemotherapy
(n=179)
Chemotherapy
(n=182)
PD
PD
Chemotherapy options:
Paclitaxel 80 mg/m2 days 1, 8, 15, and 22 q4w
Topotecan 4 mg/m2 days 1, 8, and 15 q4w
(or 1.25 mg/m2 days 1-5 q3w)
Pegylated liposomal doxorubicin 40 mg/m2 day 1 q4w
Chemotherapy
prior to
randomization
• Paclitaxel
• Topotecan
• PLD
Platinum-resistant,
recurrent epithelial ovarian,
fallopian tube, or primary
peritoneal cancer that
recurred within 6months
from the most recent
Platinum-based therapy
• ≤2 prior CT regimens
• ECOG PS 0-2
• No evidence of recto-
sigmoid involvement by
pelvic examination or
bowel involvement on CT
scan or clinical symptoms
of bowel obstruction
(N=361)
R
A
N
D
O
M
I
S
E
Pujade-Lauraine E, et al. J Clin Oncol. 2014;32:1302-1308
AURELIA: outcomes
Event
Avastin
Initiation
(N = 607)
Avastin
Throughout
(N = 608)
Control
(N = 601)
Gastrointestinal events (grade ≥2)† 17 (2.8) 16 (2.6) 7 (1.2)
Hypertension (grade ≥2)‡ 100 (16.5)§ 139 (22.9)§ 43 (7.2)
Proteinuria (grade ≥3) 4 (0.7) 10 (1.6) 4 (0.7)
Pain (grade ≥2) 252 (41.5) 286 (47.0) 250 (41.6)
Neutropenia (grade ≥4) 384 (63.3) 385 (63.3) 347 (57.7)
Febrile neutropenia 30 (4.9) 26 (4.3) 21 (3.5)
Venous thromboembolism 32 (5.3) 41 (6.7) 35 (5.8)
Arterial thromboembolism 4 (0.7) 4 (0.7) 5 (0.8)
Wound disruption 22 (3.6) 18 (3.0) 17 (2.8)
CNS bleeding 0 2 (0.3) 0
Non-CNS bleeding (grade ≥3) 8 (1.3) 13 (2.1) 5 (0.8)
Reversible posterior leukoencephalopathy syndrome 1 (0.2) 1 (0.2) 0
Burger RA et al, NEJM 2011;365: 2473-83
Bevacizumab Adverse effects
BRCA in Ca Ovary
PARP Inhibitors
BRCAmut+
SOLO2: Olaparib Maintenance
NOVA: Niraparib maintenance
Olaparib Therapy
Rucaparib Therapy
PARP Inhibitor Statergy
Ovarian Cancer: Timeline
Take Home Message
• Surgery and chemotherapy is the key to
management
• Highly responsive to chemotherapy
• Relapses are common
• Antiangiogenesis Therapy is the cornerstone
of relapsed ca ovary treatment
• Ca Ovary : The new chronic disease
“Cancer Ovary :The new chronic disease.”

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Relapsed ca ovary 2018

  • 2. Overview Ovarian cancer management Relapsed Ca Ovary Antiangiogenesis in Ca Ovary PARP Inhibitors in Ca Ovary Discussion
  • 3. Jun 2009 Dec 2012-May 2013 Jun 2014-Dec2014 Feb 2016-Jun 2016 Feb 2017-July 2017 August 2017-Nov 2017 Dec 2017-Present Day Endometriosis Bleeding PV TAH+LSO+RS RO+Omentectomy Ca Ovary Stage 1A No Residual 2nd Relapse Adenocarcinoma 6#PLD+Carboplatin:CR 4th Relapse 18#Weekly NabPaclitaxel+ Bevacizumab: PD 6th progression 3#Gemcitabine+Carboplatin + Bevcizumab ECOG PS:1 ADL:Normal CA125 Decreasing trend No Pain/Ascitis 1st Relapse Adenocarcinoma 6# Paclitaxel+ Carboplatin:CR 5th Progression 4# Topotecan+ Bevacizumab: PD Management Timeline a Case Overall Survival:8 year 6 month 36month 12 month 14 month 8 month 1 month 2 week 3rd Relapse Adenocarcinoma 6# Paclitaxel+ Carboplatin:CR
  • 6. Ovarian Carcinoma: Clinical Course Symptoms Diagnosis Chemotherapy #1 Staging Primary cytoreduction Interval Cytoreduction Progression Chemo #2 Chemo #3+ Supportive Care Death Consolidation/ Maintenance Cure Secondary CytoreductionSecond-Look
  • 8. Relapsed Carcinoma Ovary Management goals Control Disease
  • 12. Role of secondary debulking surgery Controversial but Can be tried in selective cases
  • 13. How to treat with ? Raja A.Annals of Oncology 24: 3028–3034, 2013 Platinum-combination chemotherapy in platinum-sensitive recurrent ovarian cancer
  • 16. How we treat Relapsed Ca Ovary in 2018
  • 17. Concepts of Ca ovary
  • 18. VEGF
  • 19. Angiogenesis inhibitor in carcinoma ovary
  • 20. Front-line: epithelial OV, PP or FT cancer  Stage III optimal (macroscopic)  Stage III suboptimal  Stage IV N=1,873 • Stratification variables – GOG performance status – stage/debulking status 15 months Paclitaxel (P) 175mg/m2 Carboplatin (C) AUC6 Carboplatin (C) AUC6 Paclitaxel (P) 175mg/m2 Carboplatin (C) AUC6 Paclitaxel (P) 175mg/m2 I II III Arm 1:1:1 Burger RA, et al. Gynecol Oncol. 2013;131:21-6 OV = ovarian; PP = primary peritoneal AUC: Area Under Curve GOG: Gynaecologic Oncology Group R A N D O M I S E Placebo Q3W Placebo Q3W Bevacizumab 15mg/kg Bev 15mg/kg Bevacizumab in Platinum Sensitive Ca Ovary: GOG 218 Trial
  • 21. Burger RA, et al. Gynecol Oncol. 2013;131:21-6. CP  Placebo (n=625) Bev + CP  Bev (n=623) Median PFS (months) 12.0 18.2 HR=0.62 (95% CI, 0.52–0.75) P<0.0001 ITT PFS :Significantly increased PFS with continued Bevacizumab compared to standard chemotherapy GOG 218: Outcomes CP  Placebo (n=625) Bev + CP  Bev (n=623) Median OS (months) 40.6 43.8 HR=0.62 (95% CI, 0.75–1.04) P<0.0641 Median OS trending towards benefit in ITT population
  • 22. Bevacizumab in Platinum Resistant Ca Ovary: AURELIA Trial Randomized Phase III clinical trial in Platinum Resistant Ovarian Cancer Bevacizumab 10 mg/kg q2w* + chemotherapy (n=179) Chemotherapy (n=182) PD PD Chemotherapy options: Paclitaxel 80 mg/m2 days 1, 8, 15, and 22 q4w Topotecan 4 mg/m2 days 1, 8, and 15 q4w (or 1.25 mg/m2 days 1-5 q3w) Pegylated liposomal doxorubicin 40 mg/m2 day 1 q4w Chemotherapy prior to randomization • Paclitaxel • Topotecan • PLD Platinum-resistant, recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer that recurred within 6months from the most recent Platinum-based therapy • ≤2 prior CT regimens • ECOG PS 0-2 • No evidence of recto- sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction (N=361) R A N D O M I S E Pujade-Lauraine E, et al. J Clin Oncol. 2014;32:1302-1308
  • 24. Event Avastin Initiation (N = 607) Avastin Throughout (N = 608) Control (N = 601) Gastrointestinal events (grade ≥2)† 17 (2.8) 16 (2.6) 7 (1.2) Hypertension (grade ≥2)‡ 100 (16.5)§ 139 (22.9)§ 43 (7.2) Proteinuria (grade ≥3) 4 (0.7) 10 (1.6) 4 (0.7) Pain (grade ≥2) 252 (41.5) 286 (47.0) 250 (41.6) Neutropenia (grade ≥4) 384 (63.3) 385 (63.3) 347 (57.7) Febrile neutropenia 30 (4.9) 26 (4.3) 21 (3.5) Venous thromboembolism 32 (5.3) 41 (6.7) 35 (5.8) Arterial thromboembolism 4 (0.7) 4 (0.7) 5 (0.8) Wound disruption 22 (3.6) 18 (3.0) 17 (2.8) CNS bleeding 0 2 (0.3) 0 Non-CNS bleeding (grade ≥3) 8 (1.3) 13 (2.1) 5 (0.8) Reversible posterior leukoencephalopathy syndrome 1 (0.2) 1 (0.2) 0 Burger RA et al, NEJM 2011;365: 2473-83 Bevacizumab Adverse effects
  • 25. BRCA in Ca Ovary
  • 33. Take Home Message • Surgery and chemotherapy is the key to management • Highly responsive to chemotherapy • Relapses are common • Antiangiogenesis Therapy is the cornerstone of relapsed ca ovary treatment • Ca Ovary : The new chronic disease
  • 34. “Cancer Ovary :The new chronic disease.”

Editor's Notes

  1. 6
  2. 2008
  3. * Adverse events were those with onset between cycle 2 and 30 days after the date of the last treatment. CNS denotes central nervous system. † Gastrointestinal events of grade 2 or greater were gastrointestinal-wall disruption: perforation, fistula, necrosis, or anastomotic leak. ‡ Hypertension of grade 2 or greater consisted of recurrent or continuous hypertension for a period of more than 24 hours or symptomatic increase in blood pressure by more than 20 mm Hg (diastolic) or to over 150/100 mm Hg if the blood pressure was previously within the normal range. § P<0.05 for the comparison with the control group.