Dr. Shadi Alkhayyat. MBBS,FRCPC

Assistant Professor Of Medicine and Oncology

King Abdulaziz University

Overview Statistics.

Defining Recurrence.

Discussion will be limited to Epithelial Ovarian Cancer.

Platinum-Sensitive Ovarian Cancer.

Platinum-Resistant Ovarian Cancer.

Carboplatin and Paclitaxel standard first line.

Follow up :

3-monthly review for 2 years.

6-monthly review for 3 years.

Annual review subsequently.

Each visit ( clinical assessment , +/- CA 125).

No clear evidence for routine CT radiological assessment.

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.

Relapse CA 125 is used to follow patient with ovarian cancer.

CA 125 rises 3-4 months before clinical symptoms.

Serologic relapse.

MRC OVO5/EORTC 55955

Early versus Delayed treatment.

1442 patients were randomized to early versus delayed second line treatment.

MRC OV05/EORTC 55955

Rushtin G,Volume 376, No. 9747, p1155–1163, 2 October 2010

MRC OV05/EORTC 55955 Conclusion Early chemotherapy did not improve overall survival

It was associated with mild worsening in quality of life.

Platinum-Free Interval Platinum-Sensitive Disease Platinum-Resistant Disease

Interval is 6 months or more Interval is less than 6 months.

Progression while on chemotherapy

(Refractory ovarian cancer)

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.

Gynecologic Cancer Intergroup

ORR 47% Vs 31%

PFS 8.6 m Vs 5.8 m

OS 18m Vs 17.3m

Gynecologic Cancer Intergroup

ICON 4/AGO-OVAR 2.2

ICON 4/AGO-OVAR 2.2

Parmar MK, et al. Lancet. 2003;361:2099-2106

CALYPSO Trial

PFS 11.3m Vs 9.4m

OS 33m Vs 31m

Equivalent data with less side effects.

Waqner U, Br J Cancer 2012 Aug 7;107(4):588-91.

CALYPSO Trial

Waqner U, Br J Cancer 2012 Aug 7;107(4):588-91

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.

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

Role of Bevacizumab Bevacizumab is an angiogenic inhibitor.

Ovarian cancer expresses VEGF and VEGF receptors.

In GOG 170D, Bevacizumab shows response as single agent.

Eskender R, Biologics. 2011; 5: 1–5.

OCEAN Trial

Aghajanian C, J Clin Oncol. 2012 Jun 10;30(17):2039-45

OCEAN Trial

Aghajanian C, J Clin Oncol. 2012 Jun 10;30(17):2039-45

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.

Other single agent used are:

Gemcitabine

Etoposide

Docetaxel

Pemetrexate

Role of Bevacizumab As monotherapy, GOG 170D had limited number who

showed response.

In ASCO 2012,

Bevacizumab showed significant improve in ORR and PFS.

AURELIA Study

Pujade-Lauraine E, J Clin Oncol. 2014 May 1;32(13):1302-8

AURELIA Study

Pujade-Lauraine E, J Clin Oncol. 2014 May 1;32(13):1302-8

AURELIA Study Progression-free

Survival Overall Response Rate

10 months Vs 4 months 52% Vs 29% Paclitaxel

6 months Vs 2 months 23% Vs 3% Topotecan

5 months Vs 4 Months 18% Vs 8% Liposomal Doxorubicin

Pujade-Lauraine E, J Clin Oncol. 2014 May 1;32(13):1302-8

Combination Chemotherapy In GINECO trial,

Paclitaxel

Platinum Resistant Cancer

Paclitaxel and Topotecan Paclitaxel and Carboplatin

Overall response rate similar.

Progression-Free Survival not different

Febrile neutropenia increased 4- times in combination arm.

How long to continue therapy? Survival improved with chemotherapy compared to

best supportive care.

Overall

Survival BSC Overall Survival Chemotherapy

Line of Chemotherapy

4 months 14 months Second Line

3 months 11 months Third Line

3 months 8 months Fourth Line

Hormonal therapy:

Fulvestrant, Tamoxifen or Letrozole.

Targeted therapy.

Summary Relapse is common in ovarian cancer.

Platinum-Free Interval

Cytoreduction

Platinum Sensitive Disease:

Combination is superior to single agent.

Retreatment is usually successful.

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