Second line chemotherapy for ovarian cancer

1. Second Line Chemotherapy for
Ovarian Cancer
Dr. Shadi Alkhayyat. MBBS,FRCPC
Assistant Professor Of Medicine and
Oncology.
King Abdulaziz University

2. • Definitions.
• Defining Recurrence.
• Discussion will be limited to Epithelial Ovarian
Cancer.
• Platinum-Sensitive Ovarian Cancer
• Platinum-Resistant Ovarian Cancer

3. • Relapse is common in ovarian cancer.
• Up to 60%.
• Platinum-Free Interval:
1- Predictor for response to chemotherapy.
2- Prognostic factors for PFS and OS.
3- Predictor for outcome with cytoreduction.

4. Platinum-Free Interval
Platinum-Sensitive Disease
• Interval is 6 months or more
Platinum-Resistant Disease
• Interval is less than 6
months.
• Progression while on
chemotherapy
(Refractory ovarian cancer)

5. Relapse
• CA 125 is used to follow patient with ovarian
cancer.
• Serologic relapse.
• Early versus Delayed treatment.
1- No survival difference.
2- Worse quality of life.

6. MRC OV05/EORTC 55955
Rushtin G,Volume 376, No. 9747, p1155–1163, 2 October 2010

7. Platinum-Sensitive Disease
• Retreatment with same protocol.
• Combination is superior to single agent.
• Secondary cytoreduction.
• Multiple combinations
Carboplatin and Paclitaxel
Carboplatin and Liposomal doxorubicin
Carboplatin and Gemcitabine.

8. Gynecologic Cancer Intergroup
• ORR 47% Vs 31%
• PFS 8.6 m Vs 5.8 m
• OS 18m Vs 17.3m

9. Gynecologic Cancer Intergroup

10. ICON 4/AGO-OVAR 2.2

11. ICON 4/AGO-OVAR 2.2

12. CALYPSO Trial
• PFS 11.3m Vs 9.4m
• OS 33m Vs 31m
• Equivalent data with
less side effects.

13. CALYPSO Trial

14. Trabectedin
• If platinum can not be used, combination of
Liposomal doxorubicin and Trabectedin is an
option.
• OVA-301 showed better ORR, PFS with no
difference on OS.

15. Patients who are not candidate for
combination chemotherapy
• Single agent showed good response.
• Multiple agent are approved
1- Topotecan 2- Gemcitabine.
3- Liposomal Doxorubicin
4- Trabectedin 5- Nab-Paclitaxel

16. Role of Bevacizumab
• Bevacizumab is an angiogenic inhibitor.
• Ovarian cancer expresses VEGF and VEGF
receptors.
• In GOG 170D, Bevacizumab shows response as
single agent.

17. OCEAN Trial

18. OCEAN Trial

19. • Adding Bevacizumab is not standard of care.
• Criticism of the chemotherapy backbone.

20. Platinum-Resistant Disease
• Single agent is more preferable.
• Bevacizumab has better role in combination.
• Cochrane review:
Paclitaxel
Liposomal Doxorubicin
Topotecan
• Depends on Initial therapy, side effects profile.

21. • Other single agent used are:
Gemcitabine
Etoposide
Docetaxel
Pemetrexate

22. Role of Bevacizumab
• As monotherapy, GOG 170D had limited
number who showed response.
• In ASCO 2012,
Bevacizumab showed significant improve in
ORR and PFS.

23. AURELIA Study

24. AURELIA Study

25. AURELIA Study
Progression-free SurvivalOverall Response Rate
10 months Vs 4 months52% Vs 29%Paclitaxel
6 months Vs 2 months23% Vs 3%Topotecan
5 months Vs 4 Months18% Vs 8%Liposomal Doxorubicin

26. Combination Chemotherapy
• In GINECO trial,
Paclitaxel
Platinum Resistant
Cancer
Paclitaxel and Topotecan Paclitaxel and Carboplatin

27. • Overall response rate similar.
• Progression-Free Survival not different
• Febrile neutropenia increased 4- times in
combination arm.

28. How long to continue therapy?
• Survival improved with chemotherapy
compared to best supportive care.
Overall Survival
BSC
Overall Survival
Chemotherapy
Line of Chemotherapy
4 months14 monthsSecond Line
3 months11 monthsThird Line
3 months8 monthsFourth Line

29. • Hormonal therapy:
Fulvestrant, Tamoxifen or Letrozole.
• Targeted therapy.

30. Take home
• Relapse is common in ovarian cancer.
• Platinum-Free Interval
• Cytoreduction
• Platinum Sensitive Disease:
Combination is superior to single agent.
Retreatment is usually successful.

31. • Platinum Resistant Disease:
Single agent depending on initial chemotherapy
and side effects.
Adding Bevacizumab to single chemotherapy
improve survival and response.
• Further lines improve survival.
• Patient performance status need to be
considered