recent advances in ca ovary in surgery,chemotherapy and targetted therapy discussed in detail

1. RECENT ADVANCES IN THE
MANAGEMENT OF OVARIAN
CANCER
Dr Sadia Sadiq
Consultant Oncologist(FCPS)
INMOL Hospital,Lahore

2. OBJECTIVES
• Epidemiology
• Treatment of early stage ovarian cancer
• 2nd Look Surgery
• Maintenance therapy
• Intraperitoneal chemotherapy
• HIPEC

3. • Approximately 314 000 new ovarian cancer cases and 207 000 deaths
occurred in 2020.
• There were marked geographic variations in incidence rates, with the
highest rates observed in European countries with very high HDI and
low rates were found in African countries within the lowest HDI
group.

4. • Relative to 2020 estimates, our projection for 2040 indicates
approximately 96% and 100% increase in new ovarian cancer cases
and deaths, respectively, among low HDI countries compared to 19%
and 28% in very high HDI countries.

5. GLOBOCAN 2020:PAKISTAN

6. 18th
14th

11. ICON-1
10%
Improved
RFS and
9%
Improved
OS
Optimal treatment of early-stage ovarian cancer
ACTION
TRIAL
5-year RFS
68% vs 76 %
and
5-year OS
78% vs 85%

12. Carboplatin/Paclitaxel:SOC

13. DESKTOP III - BACKGROUND
• Role of secondary cytoreductive surgery not fully defined for recurrent ovarian
cancer through prospectively randomized trials
• DESKTOP I and II trials developed, evaluated AGO Score metric to identify
patients with complete resection during secondary cytoreductive surgery
• AGO Score based on good ECOG PS (0), complete resection during first-line therapy,
ascites < 500 mL
• Positive AGO Score predicted complete resection with 95% probability
DESKTOP III trial was designed to evaluate survival benefit of secondary
cytoreductive surgery in selected patients with platinum-sensitive recurrent
ovarian cancer

17. MAINTENANCE THERAPY
• 1.BEVACIZUMAB
• 2.PARP INHIBITORS
• 3.WHATS NEW?

18. Addition of Bevacizumab to chemotherapy
1st Line

19. Addition of Bevacizumab to Chemotherapy
2nd Line
Platinum Sensitive Platinum Resistant

21. BRCA Mutations and Ovarian Cancer
• BRCA genes encode enzymes
that repair double-strand DNA
breaks
• Mutations in BRCA1 or BRCA2
• Prognostic marker for increased
risk of ovarian cancer
• Prognostic marker for increased
survival
• Predictive marker for enhanced
PARP inhibitor activity
Risk of Developing Ovarian Cancer
Mutated BRCA1
39% to 46%
Mutated BRCA2
10% to 27%
Normal BRCA
2%
Slide credit: clinicaloptions.com
https://www.acog.org/Patients/FAQs/BRCA1-and-BRCA2-Mutations

23. HRD and BRCA Mutations
Germline BRCA
mutations
Germline non-BRCA
mutations in HR pathway
Sporadic (somatic) BRCA
mutations
Sporadic non-BRCA
mutations in HR pathway
Mutations in HR pathway
↓
HRD
Slide credit: clinicaloptions.com

24. PARP Inhibitors and Homologous
Recombination

25. Current Treatment Landscape for PARPi in Ovarian
Cancer
Slide credit: clinicaloptions.com
Under investigation
FDA approved
y
Symptoms
Diagnosis
Chemo
#1
Staging/debulking
Evaluation
Progression
Chemo
#2
Chemo
#3
T
Supportive
care
Death
Chemo
#4+
T
Maintenance M M
Concomitant Concomitant
LaFargue. Lancet Oncol. 2019;20:e15.

26. PARP Inhibitors: Current Indications
Slide credit: clinicaloptions.com
Olaparib PI 2018; Rucaparib PI 2018; Niraparib PI 2019.

27. PARP INHIBITORS:PHASE 3 TRIALS
PFS PFS (BRCAm)
Olaparib-1st line SOLO 1 3 y 60 % v 27 % same
Olaparib-pl.sen.
recurrence
SOLO 2 19.1 v 5.5 months same
Niraparib-pl. sen.
recurrence
NOVA NR Median 21 v 5.5
months
Rucaparib-pl.sen.
recurrence
ARIEL 3 10.8 v 5.4 months 16.6 v 5.4 months

28. PAOLA-1 Phase III Trial: Final
Overall Survival Results of Maintenance
Olaparib + Bevacizumab in Patients With
Newly Diagnosed Advanced Ovarian Cancer
Supported by educational grants from AstraZeneca; Bristol Myers Squibb;
Exelixis, Inc.; Gilead Sciences, Inc.; and Merck Sharp & Dohme Corp.
CCO Independent Conference Coverage*
of the ESMO 2022 Annual Congress; September 9-13, 2022; Paris, France
*CCO is an independent medical education company that provides state-of-the-art medical information to
healthcare professionals through conference coverage and other educational programs.

31. LYNPARZA + bevacizumab demonstrated a clinically
significant median PFS benefit of 3.9 years vs 1.5 years with
bevacizumab + placebo in HRD-positive patients

32. ROLE OF IMMUNOTHERAPY
• Immunotherapy has proved effective in a number of recurrent
cancers but has been less successful for patients with ovarian cancer.
• Pembrolizumab RR 10%
• Nivolumab as a single agent or combined with ipilimumab RR 30%
• Niraparib plus Pembro RR 18%

33. INTRAPERITONEAL THERAPY

36. GOG 252 TRIAL

37. No significant advantage in progression-free or overall survival was observed in optimally
resected patients with stage III disease given either intraperitoneal chemotherapy regimen compared with
the intravenous-only arm after a median follow-up of 85 months.
The quality of life was best in the intravenous arm.

38. HIPEC

39. N Engl J Med 2018;378:230-40. DOI: 10.1056/NEJMoa1708618
Copyright © 2018 Massachusetts Medical Society.
Multicenter, open-label, phase 3 trial
assigned 245 patients who had at least SD after 3 cycles of carbo/pacli
to undergo interval cytoreductive surgery
either with or without administration of HIPEC with cisplatin (100 mg/m2).
3 more cycles were administered postoperatively.
The primary end point was RFS.
OS and the SE profile were key secondary end points
OVHIPEC-01

41. JAMA Surg. 2022;157(5):374-383.
doi:10.1001/jamasurg.2022.0143 Published online March 9,
2022.

43. Median
PFS
15.4 v
17.4 m
Median
OS
48.2 v
61.8m

44. OVHIPEC-02
The objective of this study is to prove that treatment with primary cytoreductive surgery in combination
with HIPEC (treatment arm) improves outcome compared to primary cytoreductive surgery without
HIPEC (standard arm) with acceptable morbidity, in patients with FIGO stage III epithelial ovarian cancer
who are eligible for primary cytoreductive surgery with no residual disease, or residual disease up to 2.5
mm.

45. SEER registry of survival rates for ovarian cancer by stage and time since diagnosis

46. THANK YOU !
• Through ongoing advances, we hope that ovarian cancer will
transition from a historically highly fatal disease to a chronic
but treatable illness, and, increasingly, to one that is curable,