1 of 76

Adjuvant ttt of Ovarian Cancer between past and present

Presented by :

Heba bakri , MD

Assiut university , Egypt

8th GO 12/12/2024

2 of 76

Disclosures :

  • Speaker’s honoraria:

AstraZeneca , Roche , Amgen , Novartis , Janssen , MSD

​

  • Travel grants: AstraZeneca , Janssen , Pierre Fabre , MSD

​

3 of 76

Agenda :

​

  • History of ovarian cancer treatment In the adjuvant setting
  • PARPi revolution ---- Olaparib single or in combination
  • Tools to Predict response / resistance to PARPI before its usage
  • Un met needs in adjuvant setting
  • Wrap up

​

​

4 of 76

5 of 76

6 of 76

Back to ovarian cancer ☺))

7 of 76

8 of 76

9 of 76

10 of 76

11 of 76

Sooo , For more than 2 decades

​

​

  • Carboplatin and paclitaxel established as the backbone of chemotherapy for ovarian cancer

​

​

• No biomarkers, all histologies treated similarly

​

​

• Recognition that surgical residual disease is a major prognostic factor with implications for surgical expertise and centralization

12 of 76

�Anti-angiogenic therapy in ovarian cancer

13 of 76

  • VEGF over-expressed in human ovarian tumours

​

•VEGF associated with development of ascites and carcinomatosis

​

  • VEGF expression associated with poor prognosis

​

​

• VEGF antibodies inhibit SKOV-3 tumour growth and ascites formation

​

​

14 of 76

15 of 76

16 of 76

17 of 76

Overall survival

18 of 76

19 of 76

​

Bevacizumab first molecularly targeted therapy in front-line treatment of ovarian cancer

20 of 76

For another decade ,,,,,

  • Bevacizumab has become a backbone of treatment for advanced ovarian cancer stage III- IV with PFS improvement , OS in high risk patients only

​

  • No biological predictors of response- a clinical decision based on prognostic factors, stage, residual disease and KELIM score

​

  • Lower dose and shorter treatment is not inferior

​

  • No benefit from increasing duration of therapy

21 of 76

22 of 76

23 of 76

SOC in adjuvant setting till 2018

24 of 76

25 of 76

26 of 76

27 of 76

Pathological and Molecular Subtypes of Ovarian cancers

28 of 76

29 of 76

30 of 76

31 of 76

32 of 76

33 of 76

34 of 76

35 of 76

What is the situation in Adjuvant setting ?

36 of 76

37 of 76

​

  • Patients with BRCA mutation have a longer PFS than BRCA wild type

​

  • Relapse still occurs in most patients of these patients within 3 years of diagnosis

​

38 of 76

39 of 76

Olaparib

Niraparib

Rucaparib

40 of 76

Study with the lower proportion of

“higher-risk” features :

-2/3 PCS & 75% Non Visible Residual Disease

-17% Stage IV

41 of 76

42 of 76

43 of 76

44 of 76

45 of 76

46 of 76

What about PARPi combo ?

47 of 76

48 of 76

49 of 76

50 of 76

51 of 76

52 of 76

53 of 76

54 of 76

55 of 76

56 of 76

Is it worthy addition of bevacizumab to PARPi ??

57 of 76

58 of 76

59 of 76

60 of 76

61 of 76

62 of 76

��What are surrogates for HRD positive / PARPi response ?

63 of 76

64 of 76

65 of 76

66 of 76

Although all efforts to improve survival , Still there is Un met needs in the adjuvant setting

67 of 76

  • Although 50% cured at 5 years >>>>> 50% relapse
  • PARP resistance and progression in first 6 m

68 of 76

69 of 76

70 of 76

Take home messages

71 of 76

72 of 76

73 of 76

74 of 76

​

  • Overall survival benefit in BRCAmut ovarian cancer has led to a change in clinical practice
  • Testing for germline and somatic BRCAmut is now part of routine clinical practice
  • Tumours with Homologous Recombination Repair deficiency beyond BRCA also benefit from PARPi therapy

75 of 76

​

  • New and better treatments are still needed to further improve outcomes

​

  • Research needed to explore how best to treat women with relapsed ovarian cancer after first-line maintenance treatment with a PARPi

​

76 of 76