Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

surgical candidate, intraoperative histology confirmed disease

1st line – surgical staging ± debulking surgery

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
1st line – 

surgical staging ± debulking surgery

Surgery is required for histological diagnosis, staging, and tumour debulking, and is the primary treatment in suitable patients.

Surgery performed by an experienced gynaecological oncologist has been found to be associated with improved survival outcomes.[19][118][119][120][121]

Genetic risk evaluation and genetic testing (e.g., for BRCA1 and BRCA2 mutations, and other ovarian cancer susceptibility genes) should be carried out if not done previously.[79][90] In the absence of a germline BRCA mutation, somatic tumour testing for BRCA mutations and homologous recombination deficiency (HRD) status is recommended.[19][79][90]

Comprehensive surgical staging and staging biopsies are indicated if intraoperative histology confirms the presence of an ovarian carcinoma.

Surgical staging is required to assess the extent of disease; up to 30% of patients with apparent early-stage ovarian cancer may be upstaged with comprehensive staging.[91][122]

Surgical staging usually includes total abdominal hysterectomy, bilateral salpingo-oophorectomy, appendectomy (if the appendix appears abnormal in patients with suspected or confirmed mucinous ovarian tumours), omentectomy, pelvic and para-aortic lymph node dissection, pelvic washings, and peritoneal biopsies.[123][124]

There is controversy regarding the benefits of performing systematic pelvic and para-aortic lymph node dissection during surgery.[125][126]​ National Comprehensive Cancer Network (NCCN) guidelines recommend pelvic and para-aortic lymph node dissection only for patients with disease confined to affected ovaries or to the pelvis, and for those with more extensive disease with tumour nodules ≤2 cm outside the pelvis. For those with more extensive disease outside the pelvis (nodules >2 cm), suspicious or enlarged nodes should be resected if possible.[19]

Hysterectomy and bilateral salpingo-oophorectomy are usually carried out during comprehensive surgical staging. However, selected patients with early-stage low-risk disease (i.e., stage 1A or IB, grade 1 or 2) who want to preserve fertility can be considered for fertility-sparing staging surgery, which involves preserving the uterus and the contralateral ovary and fallopian tube. Preoperative evaluation by a reproductive endocrinologist is recommended for women who wish to preserve fertility. Completion surgery should be considered after childbearing is completed for women who have a fertility-sparing procedure.[19]

Patients with stage II, III, or IV disease at surgical staging require maximal surgical effort to debulk all tumour deposits (i.e., complete cytoreduction [R0]), including removal of all gross residual disease from the abdomen, pelvis, and retroperitoneum. Complete cytoreduction is the current standard of care, although most of the evidence supporting this approach is from retrospective studies.​[19][90]​​​​​[118]

If complete cytoreduction is not possible, optimal cytoreduction should be the surgical goal (i.e., residual disease <1 cm). Patients who are optimally debulked have improved survival compared with those with extensive residual disease following primary debulking surgery.[118]

Other surgical procedures may be performed during debulking surgery to achieve complete or optimal cytoreduction, including bowel resection, diaphragm stripping, and splenectomy. Although this is associated with increased surgical risk and morbidity, it is usually balanced by significant improvement in survival.[118][127][128]

Laparoscopy may be used in patients with advanced disease to assess if complete or optimal cytoreduction can be achieved with debulking surgery.[19][129]

Most patients require adjuvant chemotherapy after surgical staging and debulking surgery. Adjuvant chemotherapy is used to eradicate any residual microscopic or sub-centimetre tumours following complete or optimal cytoreduction.

Plus – observation

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
|
stage IA or IB (grade 1 or 2) disease
Plus – 

observation

Treatment recommended for ALL patients in selected patient group

Patients with early-stage low-risk disease (stage IA or IB) and favourable tumour characteristics (grade 1 or 2 disease) do not require adjuvant chemotherapy after comprehensive surgical staging because this has not been found to improve survival in these patients.[131][132]

Observation after surgical staging is recommended as long as comprehensive surgical staging has been carried out.[19][91]​​​[133]​ Up to 30% of patients with apparent early-stage ovarian cancer may be upstaged with comprehensive staging.[91][122]

Plus – adjuvant platinum-based chemotherapy

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
|
stage IA or IB (grade 3) disease, or stage IC disease
Plus – 

adjuvant platinum-based chemotherapy

Treatment recommended for ALL patients in selected patient group

Patients with early-stage disease who have poor tumour characteristics (stage IA or IB, and grade 3 disease) or a high risk of recurrence (stage IC disease) require adjuvant platinum-based chemotherapy after comprehensive surgical staging.

Paclitaxel plus carboplatin is the regimen of choice for adjuvant chemotherapy.[134]

Docetaxel plus carboplatin is an alternative option for patients who are allergic to or intolerant of paclitaxel.[135][136]

Carboplatin plus liposomal doxorubicin may also be considered.[19][137]

Efficacy appears to be similar for the recommended treatment regimens, but differing toxicity profiles should be taken into account.[19]

Adjuvant chemotherapy is typically given intravenously for 3 to 6 cycles.

In the Gynecologic Oncology Group (GOG) 157 study, recurrence rate with 6 cycles of paclitaxel plus carboplatin was 24% lower than with 3 cycles in patients with early-stage high-risk disease, but this finding was not statistically significant.[134] Using 6 cycles was associated with more toxicity (e.g., neurotoxicity, anaemia, and granulocytopenia).[134]

The decision to treat with 3 or more cycles of chemotherapy is one made by the physician and the patient, acknowledging the findings of the GOG study.

A reasonable treatment strategy is to plan for 3 cycles of chemotherapy and evaluate adverse effects and toxicity. If 3 cycles of chemotherapy are well tolerated, up to 3 more cycles of treatment may be considered.

Primary options

paclitaxel

and

carboplatin

Secondary options

doxorubicin liposomal

and

carboplatin

OR

docetaxel

and

carboplatin

Plus – adjuvant platinum-based chemotherapy

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
|
stage II, III, or IV disease (completely or optimally debulked)
Plus – 

adjuvant platinum-based chemotherapy

Treatment recommended for ALL patients in selected patient group

Patients with stage II, III, or IV disease require adjuvant platinum-based chemotherapy (e.g., paclitaxel plus carboplatin) after surgical staging and debulking surgery.[138] Adjuvant chemotherapy is typically given for 6 cycles.

Docetaxel plus carboplatin is an alternative for patients allergic to or intolerant of paclitaxel.[135][136]

Carboplatin plus liposomal doxorubicin may also be considered as an alternative option.[19][137]

Efficacy appears to be similar for the recommended treatment regimens, but differing toxicity profiles should be taken into account.[19]

Dose-dense or weekly dosing regimens for paclitaxel plus carboplatin may be considered instead of conventional 3-weekly dosing for certain patients with stage II, III, or IV disease (e.g., weekly paclitaxel plus weekly carboplatin for older or frail patients), although the evidence is equivocal.[19]​​​[90]​​[140]​​​​​​[141][142][143][144]​​​​

Patients with stage II or III disease who undergo complete or optimal debulking surgery (i.e., residual disease <1 cm) may be considered for adjuvant intraperitoneal chemotherapy instead of conventional intravenous chemotherapy.

Intraperitoneal chemotherapy is administered directly to the peritoneal cavity via a subcutaneous port placed in the abdomen during surgery. The peritoneal surface is the main site of recurrence in patients with ovarian cancer.[150] Patients with good performance status must be carefully selected for intraperitoneal chemotherapy.[151] [ Cochrane Clinical Answers logo ] ​​ Intravenous chemotherapy should be used if intraperitoneal chemotherapy is unsuitable.

Randomised clinical trials have found a survival benefit with intraperitoneal chemotherapy compared with intravenous chemotherapy in patients with optimally debulked stage III disease.[152][153][154][155]​​ Although a survival benefit has not been demonstrated in patients with optimally debulked stage II disease, guidelines recommend that these patients should be considered for intraperitoneal chemotherapy.[19][156][157]​​ Intraperitoneal chemotherapy is not recommended for stage I or IV disease.[19]

Compared with intravenous therapy alone (paclitaxel plus cisplatin), intravenous paclitaxel plus intraperitoneal cisplatin and intraperitoneal paclitaxel, given for 6 cycles, improves survival in patients with optimally debulked stage III ovarian cancer.[152] [ Cochrane Clinical Answers logo ]

Primary options

paclitaxel

and

carboplatin

Secondary options

docetaxel

and

carboplatin

OR

doxorubicin liposomal

and

carboplatin

OR

paclitaxel

and

cisplatin

Consider – bevacizumab

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
|
stage II, III, or IV disease (completely or optimally debulked)
Consider – 

bevacizumab

Additional treatment recommended for SOME patients in selected patient group

Combining bevacizumab (a humanised monoclonal antibody that targets vascular endothelial growth factor) with adjuvant paclitaxel plus carboplatin or docetaxel plus carboplatin may also be considered in patients with stage III or IV disease.

In the GOG 218 study and the ICON7 study, the addition of bevacizumab to adjuvant paclitaxel plus carboplatin in patients with advanced disease improved progression-free survival (but not overall survival) compared with paclitaxel plus carboplatin alone.[145][146][147][148]

A subgroup analysis of the ICON7 study reported improved overall survival in certain high-risk patients receiving bevacizumab, including those with suboptimally debulked stage III disease, stage IV disease, or inoperable disease.[149]

Combining bevacizumab with intraperitoneal chemotherapy is not recommended because it has not been shown to improve progression-free survival compared with bevacizumab plus intravenous chemotherapy.[19][157]

Primary options

bevacizumab

Consider – maintenance therapy

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
|
stage II, III, or IV disease (completely or optimally debulked)
Consider – 

maintenance therapy

Additional treatment recommended for SOME patients in selected patient group

Patients with stage II, III, or IV disease who achieve a complete or partial response following initial treatment can be considered for maintenance therapy with bevacizumab and/or a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor.

Bevacizumab is recommended as an option for maintenance therapy in patients without a BRCA1 or BRCA2 mutation, or with unknown mutation status, who are in complete or partial response after first-line chemotherapy that included bevacizumab.[19] Maintenance bevacizumab has demonstrated improved progression-free survival, but not overall survival.[145][146][147][148]

PARP inhibitors (e.g., olaparib, niraparib, rucaparib) target cancer cells with homologous recombination DNA repair deficiency caused by genetic mutations (e.g., BRCA) or genetic instability.[176] PARP inhibitors have shown improved outcomes in patients with a BRCA1 or BRCA2 mutation compared with bevacizumab.

Olaparib, niraparib, or rucaparib are recommended for maintenance therapy in patients with stage II, III, or IV disease with a BRCA1 or BRCA2 mutation, who are in complete or partial response after first-line chemotherapy.[19][90]​ Olaparib may be used in combination with bevacizumab in patients with a BRCA1 or BRCA2 mutation, or who are homologous recombination deficient (HRD), if first-line chemotherapy included bevacizumab; niraparib may be used in combination with bevacizumab if the patient is unable to tolerate olaparib.[19] 

For patients without a BRCA1 or BRCA2 mutation, or with unknown mutation status, who are in complete or partial response after first-line chemotherapy that did not include bevacizumab, options include observation (if complete response), or maintenance niraparib or rucaparib.[19]

Maintenance therapy with PARP inhibitors can be continued until disease progression or unacceptable toxicity for up to: 2 years for olaparib; 3 years for niraparib; 2 years for rucaparib; 15 months for bevacizumab.[19]

Maintenance bevacizumab in combination with a PARP inhibitor is only considered for patients who received bevacizumab during first-line chemotherapy.[19][90]​​​​​​[173]

There have been reports of severe hypertension and posterior reversible encephalopathy syndrome (PRES) associated with niraparib, with some cases occurring within the first month of treatment.[177]​ Niraparib should be discontinued if hypertensive crisis occurs or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, and if PRES is suspected or confirmed.

Although data are limited for stage II disease, the NCCN guidelines recommend considering PARP inhibitor maintenance treatment for patients with stage II disease with complete or partial response to first-line treatment.[19] These maintenance therapy options are not recommended for stage I disease.[19]​ Observation may be considered for select patients with stage II disease with a complete response after first-line chemotherapy that did not include bevacizumab.[19] 

Confirm BRCA and HRD status before initiating maintenance therapy with a PARP inhibitor following first-line treatment.[90]​​​

The use of chemotherapy for maintenance therapy is not recommended because of toxicity and the lack of survival benefit.[19][174][175]

Primary options

bevacizumab

OR

olaparib

OR

niraparib

OR

rucaparib

OR

bevacizumab

and

olaparib

Secondary options

bevacizumab

and

niraparib

Plus – adjuvant platinum-based chemotherapy

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
|
stage II, III, or IV disease (suboptimally debulked)
Plus – 

adjuvant platinum-based chemotherapy

Treatment recommended for ALL patients in selected patient group

Patients with suboptimally debulked stage II, III, or IV disease (i.e., residual disease >1 cm after primary debulking surgery) require adjuvant platinum-based chemotherapy.

The current standard of care is paclitaxel plus carboplatin given intravenously. Adjuvant chemotherapy is typically given for 6 cycles.

Docetaxel plus carboplatin is an alternative for patients allergic to or intolerant of paclitaxel.[19][135]

Carboplatin plus liposomal doxorubicin may also be considered in these patients.[19][137]

Efficacy appears to be similar for the recommended treatment regimens, but differing toxicity profiles should be taken into account.[19]

Dose-dense or weekly regimens for paclitaxel plus carboplatin may be considered instead of conventional 3-weekly dosing for certain patients with stage II, III, or IV disease (e.g., weekly paclitaxel plus weekly carboplatin for older or frail patients), although the evidence is equivocal.[19]​​​[90]​​[140]​​​​​​[141][142][143][144]​​​

Primary options

paclitaxel

and

carboplatin

Secondary options

docetaxel

and

carboplatin

OR

doxorubicin liposomal

and

carboplatin

Consider – bevacizumab

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
|
stage II, III, or IV disease (suboptimally debulked)
Consider – 

bevacizumab

Additional treatment recommended for SOME patients in selected patient group

Combining bevacizumab with paclitaxel plus carboplatin may be considered in patients with suboptimally debulked stage III or IV disease.[145][146][147][148][149]

Docetaxel plus carboplatin is an alternative for patients allergic to or intolerant of paclitaxel; the addition of bevacizumab may be useful in certain circumstances.[19][135][136]

Primary options

bevacizumab

Consider – maintenance therapy

Back
ACUTE
|
surgical candidate, intraoperative histology confirmed disease
|
stage II, III, or IV disease (suboptimally debulked)
Consider – 

maintenance therapy

Additional treatment recommended for SOME patients in selected patient group

Patients with stage II, III, or IV disease who achieve a complete or partial response following initial treatment can be considered for maintenance therapy with bevacizumab and/or a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor.

Bevacizumab is recommended as an option for maintenance therapy in patients without a BRCA1 or BRCA2 mutation, or with unknown mutation status, who are in complete or partial response after first-line chemotherapy that included bevacizumab.[19] Maintenance bevacizumab has demonstrated improved progression-free survival, but not overall survival.[145][146][147][148]

PARP inhibitors (e.g., olaparib, niraparib, rucaparib) target cancer cells with homologous recombination DNA repair deficiency caused by genetic mutations (e.g., BRCA) or genetic instability.[176] PARP inhibitors have shown improved outcomes in patients with a BRCA1 or BRCA2 mutation compared with bevacizumab.

Olaparib, niraparib, or rucaparib are recommended for maintenance therapy in patients with stage II, III, or IV disease with a BRCA1 or BRCA2 mutation, who are in complete or partial response after first-line chemotherapy.[19][90]​ Olaparib may be used in combination with bevacizumab in patients with a BRCA1 or BRCA2 mutation, or who are homologous recombination deficient (HRD), if first-line chemotherapy included bevacizumab; niraparib may be used in combination with bevacizumab if the patient is unable to tolerate olaparib.[19]

For patients without a BRCA1 or BRCA2 mutation, or with unknown mutation status, who are in complete or partial response after first-line chemotherapy that did not include bevacizumab, options include observation (if complete response), or maintenance niraparib or rucaparib.[19]

Maintenance therapy with PARP inhibitors can be continued until disease progression or unacceptable toxicity, or up to: 2 years for olaparib; 3 years for niraparib; 2 years for rucaparib; 15 months for bevacizumab.[19]

Maintenance bevacizumab in combination with a PARP inhibitor is only considered for patients who received bevacizumab during first-line chemotherapy.[19][90]​​​​​​[173]

There have been reports of severe hypertension and posterior reversible encephalopathy syndrome (PRES) associated with niraparib, with some cases occurring within the first month of treatment.[177] Niraparib should be discontinued if hypertensive crisis occurs or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, and if PRES is suspected or confirmed.

Although data are limited for stage II disease, the NCCN guidelines recommend considering PARP inhibitor maintenance treatment for patients with stage II disease with complete or partial response to first-line treatment.[19] These maintenance therapy options are not recommended for stage I disease.[19]

Observation may be considered for select patients with stage II disease with a complete response after first-line chemotherapy that did not include bevacizumab.[19]

Confirm BRCA and HRD status before initiating maintenance therapy with a PARP inhibitor following first-line treatment.[90]​​​

The use of chemotherapy for maintenance therapy is not recommended because of toxicity and the lack of survival benefit.[19][174][175]

Primary options

bevacizumab

OR

olaparib

OR

niraparib

OR

rucaparib

OR

bevacizumab

and

olaparib

Secondary options

bevacizumab

and

niraparib

poor surgical candidate, biopsy confirmed disease

1st line – neoadjuvant platinum-based chemotherapy ± surgical staging and interval debulking surgery

Back
ACUTE
|
poor surgical candidate, biopsy confirmed disease
1st line – 

neoadjuvant platinum-based chemotherapy ± surgical staging and interval debulking surgery

Patients who are unsuitable for primary surgery (e.g., due to comorbidities), or those with bulky stage III to IV disease who are unlikely to achieve complete or optimal cytoreduction (i.e., residual disease <1 cm) with primary surgery, can be considered for neoadjuvant platinum-based chemotherapy and then reassessed for surgical staging and interval debulking surgery.[19][92]​​

The goals of neoadjuvant chemotherapy are to decrease the volume of disease (tumour burden) and allow time for underlying medical comorbidities to improve so that comprehensive surgical staging and optimal cytoreduction can be achieved.[158][159]

Studies report similar survival outcomes in patients with advanced disease who received neoadjuvant chemotherapy and interval debulking, and those who underwent primary surgery followed by adjuvant chemotherapy. Postoperative mortality and serious adverse events may be reduced in those receiving neoadjuvant chemotherapy.​[92][160]​​​

Patients should be evaluated by a gynaecological oncologist and have a confirmed histological diagnosis (e.g., obtained by core biopsy, or FNA if biopsy is not possible) before initiation of neoadjuvant chemotherapy. Laparoscopy may be considered to determine feasibility of optimal cytoreduction.[19][92]​​

Intravenous regimens used for adjuvant chemotherapy (e.g., paclitaxel plus carboplatin) can be used for neoadjuvant chemotherapy; 3-4 cycles are recommended before interval surgery for patients with a response to chemotherapy or stable disease (although 4-6 may be considered).[19][92]​​

Primary options

paclitaxel

and

carboplatin

Consider – adjuvant platinum-based chemotherapy

Back
ACUTE
|
poor surgical candidate, biopsy confirmed disease
Consider – 

adjuvant platinum-based chemotherapy

Additional treatment recommended for SOME patients in selected patient group

Adjuvant platinum-based chemotherapy (e.g., paclitaxel plus carboplatin) can be considered following neoadjuvant chemotherapy and interval debulking surgery, depending on disease stage.[163][164]

Any of the options for stage II, III, or IV adjuvant chemotherapy can be used. Intravenous regimens given for 3 cycles are typically used.[163][164]

Intraperitoneal regimens (e.g., paclitaxel plus cisplatin) may be considered in certain patients, but the evidence is equivocal.[165][166]

Primary options

paclitaxel

and

carboplatin

Secondary options

docetaxel

and

carboplatin

OR

doxorubicin liposomal

and

carboplatin

OR

paclitaxel

and

cisplatin

Consider – bevacizumab

Back
ACUTE
|
poor surgical candidate, biopsy confirmed disease
Consider – 

bevacizumab

Additional treatment recommended for SOME patients in selected patient group

Combining bevacizumab with neoadjuvant platinum-based chemotherapy can be considered, but this should be avoided in the cycle prior to surgery because bevacizumab may interfere with wound healing following surgery.[161][162]

Bevacizumab may also be considered in addition to adjuvant platinum-based chemotherapy for high-risk patients (stage IV, suboptimal cytoreduction), but only after adequate healing from surgery.[92]

Primary options

bevacizumab

Consider – hyperthermic intraperitoneal chemotherapy (HIPEC) (during interval debulking surgery)

Back
ACUTE
|
poor surgical candidate, biopsy confirmed disease
Consider – 

hyperthermic intraperitoneal chemotherapy (HIPEC) (during interval debulking surgery)

Additional treatment recommended for SOME patients in selected patient group

Patients with stage III disease who are undergoing interval debulking surgery can be considered for HIPEC (using cisplatin) during surgery.[19][92]​​[167][168][169]

HIPEC is similar to intraperitoneal chemotherapy in that chemotherapy is delivered directly to the peritoneal cavity. However, HIPEC is delivered under hyperthermic conditions to increase the absorption of chemotherapy at the peritoneal surface, and to increase the sensitivity of the cancer to chemotherapy.[170][171]

Consider – maintenance therapy

Back
ACUTE
|
poor surgical candidate, biopsy confirmed disease
Consider – 

maintenance therapy

Additional treatment recommended for SOME patients in selected patient group

Patients with stage II, III, or IV disease who achieve a complete or partial response following initial treatment can be considered for maintenance therapy with bevacizumab and/or a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor.

Bevacizumab is recommended as an option for maintenance therapy in patients without a BRCA1 or BRCA2 mutation, or with unknown mutation status, who are in complete or partial response after first-line chemotherapy that included bevacizumab.[19] Maintenance bevacizumab has demonstrated improved progression-free survival, but not overall survival.[145][146][147][148]

PARP inhibitors (e.g., olaparib, niraparib, rucaparib) target cancer cells with homologous recombination DNA repair deficiency caused by genetic mutations (e.g., BRCA) or genetic instability.[176] PARP inhibitors have shown improved outcomes in patients with a BRCA1 or BRCA2 mutation compared with bevacizumab.

Olaparib, niraparib, or rucaparib are recommended for maintenance therapy in patients with stage II, III, or IV disease with a BRCA1 or BRCA2 mutation, who are in complete or partial response after first-line chemotherapy.[19][90] Olaparib may be used in combination with bevacizumab in patients with a BRCA1 or BRCA2 mutation, or who are homologous recombination deficient (HRD), if first-line chemotherapy included bevacizumab; niraparib may be used in combination with bevacizumab if the patient is unable to tolerate olaparib.[19]

For patients without a BRCA1 or BRCA2 mutation, or with unknown mutation status, who are in complete or partial response after first-line chemotherapy that did not include bevacizumab, options include observation (if complete response), or maintenance niraparib or rucaparib.[19]

Maintenance therapy with PARP inhibitors can be continued until disease progression or unacceptable toxicity, or up to: 2 years for olaparib; 3 years for niraparib; 2 years for rucaparib; 15 months for bevacizumab.[19]

Maintenance bevacizumab in combination with a PARP inhibitor is only considered for patients who received bevacizumab during first-line chemotherapy.[19][90]​​​​​[173]

There have been reports of severe hypertension and posterior reversible encephalopathy syndrome (PRES) associated with niraparib, with some cases occurring within the first month of treatment.[177] Niraparib should be discontinued if hypertensive crisis occurs or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, and if PRES is suspected or confirmed.

Although data are limited for stage II disease, the NCCN guidelines recommend considering PARP inhibitor maintenance treatment for patients with stage II disease with complete or partial response to first-line treatment.[19] These maintenance therapy options are not recommended for stage I disease.[19]​ Observation may be considered for select patients with stage II disease with a complete response after first-line chemotherapy that did not include bevacizumab.[19]

Confirm BRCA or HRD status before initiating maintenance therapy with a PARP inhibitor following first-line treatment.[90]​​​

The use of chemotherapy for maintenance therapy is not recommended because of toxicity and the lack of survival benefit.[19][174][175]

Primary options

bevacizumab

OR

olaparib

OR

niraparib

OR

rucaparib

OR

bevacizumab

and

olaparib

Secondary options

bevacizumab

and

niraparib

ONGOING

platinum-sensitive recurrent disease

1st line – observation

Back
ONGOING
|
platinum-sensitive recurrent disease
|
with biochemical relapse and no clinical or radiological relapse
1st line – 

observation

Patients with platinum-sensitive recurrent disease are defined as those who relapse ≥6 months following completion of first-line platinum-based chemotherapy.

Treatment for these patients is guided by:

symptoms (e.g., gastrointestinal complaints, such as pain, nausea, emesis, or bowel obstruction [in severe cases]);

physical examination;

laboratory results (e.g., molecular analysis to confirm BRCA and homologous recombination DNA repair deficiency status, and to identify other markers that may influence management);

imaging results;

performance status.[19]

The aim of treatment is to palliate and possibly extend survival. Long-term cure is not a realistic goal of therapy in these patients; therefore, benefits of treatment must be weighed against adverse effects.

In many patients, CA-125 levels will rise before symptoms develop, or before there is evidence of disease progression on imaging (i.e., biochemical relapse, but no clinical or radiological relapse). Immediate treatment for biochemical relapse alone (raised CA-125 concentration) has not been found to improve survival.[97] In this instance, observation is an acceptable strategy.[19]

1st line – repeat (secondary) debulking surgery and/or repeat platinum-based chemotherapy

Back
ONGOING
|
platinum-sensitive recurrent disease
|
with clinical and/or radiological relapse
1st line – 

repeat (secondary) debulking surgery and/or repeat platinum-based chemotherapy

Patients with platinum-sensitive recurrent disease are defined as those who relapse ≥6 months following completion of first-line platinum-based chemotherapy.

Treatment for these patients is guided by:

symptoms (e.g., gastrointestinal complaints, such as pain, nausea, emesis, or bowel obstruction [in severe cases]);

physical examination;

laboratory results (e.g., molecular analysis to confirm BRCA or homologous recombination DNA repair deficiency status);

imaging results;

performance status.[19]

The aim of treatment is to palliate and possibly extend survival. Long-term cure is not a realistic goal of therapy in these patients; therefore, benefits of treatment must be weighed against adverse effects.

Patients with clinical and/or radiological relapse can be considered for repeat (secondary) debulking surgery followed by re-treatment with a platinum-based chemotherapy regimen.[178][179][180][181][182][183] This approach is usually only considered for patients with good performance status, no ascites, and disease that is limited to the abdominal pelvic cavity. A validated score system (e.g., AGO-OVAR score) may be used to assess patient suitability for secondary debulking surgery.[184] Patients who are deemed unsuitable for secondary debulking surgery can be re-treated with platinum-based chemotherapy.

Platinum-based chemotherapy regimens that can be considered in patients with platinum-sensitive recurrent disease include: carboplatin plus liposomal doxorubicin; carboplatin plus paclitaxel; or carboplatin plus gemcitabine.[187][188][189][190] If not used previously, bevacizumab can be combined with these regimens, and then used as a single agent for maintenance therapy.[191][192][193]

Carboplatin plus liposomal doxorubicin has demonstrated superior progression-free survival compared with carboplatin plus paclitaxel in patients with platinum-sensitive recurrent disease (11.3 vs. 9.4 months).[187] However, no significant difference in overall survival has been demonstrated.[188] Carboplatin plus liposomal doxorubicin plus bevacizumab has demonstrated improved progression-free survival compared with carboplatin plus gemcitabine plus bevacizumab (13.3 vs. 11.6 months).[193] The addition of bevacizumab to carboplatin plus paclitaxel showed improved overall survival (42.2 vs. 37.3 months).[192] Carboplatin plus gemcitabine has demonstrated improved progression-free survival compared with carboplatin alone (8.6 vs. 5.8 months), without reducing quality of life.[189]

For patients with platinum-sensitive recurrent disease who cannot tolerate combination therapy, carboplatin or cisplatin are preferred for single-agent treatment.[19]

In the recurrent disease setting, treatment is continued until there is a complete response, disease progression, or unacceptable toxicity.

Patients with platinum-sensitive recurrent disease may repeat platinum-based chemotherapy multiple times if there are multiple recurrences and if tolerated. Clinical judgement should be used for dosing to avoid excessive toxicity. However, progression-free survival and overall survival will decrease progressively with each line of therapy.[194]

Primary options

carboplatin

-- AND --

doxorubicin liposomal

or

paclitaxel

or

gemcitabine

OR

carboplatin

-- AND --

doxorubicin liposomal

or

paclitaxel

or

gemcitabine

-- AND --

bevacizumab

Secondary options

carboplatin

OR

cisplatin

Consider – maintenance therapy

Back
ONGOING
|
platinum-sensitive recurrent disease
|
with clinical and/or radiological relapse
Consider – 

maintenance therapy

Additional treatment recommended for SOME patients in selected patient group

Patients with platinum-sensitive recurrent disease who received bevacizumab as part of re-treatment with platinum-based chemotherapy can receive bevacizumab as a single agent for maintenance therapy.[19][191][192][193]

Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors (e.g., olaparib, rucaparib, or niraparib) can also be considered for maintenance therapy in patients with platinum-sensitive recurrent disease, if not previously used or if disease has not progressed on prior PARP inhibitor treatment.[19][173]

Olaparib, niraparib, and rucaparib are approved for maintenance therapy in patients with recurrent disease who are in complete or partial response to platinum-based chemotherapy.[195][196][197][198][199][200][201][202][203]

The National Comprehensive Cancer Network (NCCN) recommends PARP inhibitor maintenance therapy for patients with a BRCA1 or BRCA2 mutation in the setting of maintenance therapy for re-treated patients with platinum-sensitive recurrent disease.[19] Use of PARP inhibitors for maintenance therapy in patients with recurrence who do not have a BRCA1 or BRCA2 mutation is controversial.[19][90][173] One phase 3 trial reported detrimental overall survival with maintenance niraparib compared with placebo in patients with recurrent disease who did not have a germline BRCA mutation.[173][204]

Long-term outcome data from clinical trials and pharmacovigilance studies indicate that the risk of developing myelodysplastic syndrome and acute myeloid leukaemia is increased in patients taking PARP inhibitors, particularly those with a BRCA mutation with recurrent disease.[90][205][206][207]

Confirm BRCA status and discuss the risks and benefits of PARP inhibitors before initiating maintenance therapy with a PARP inhibitor in patients with recurrent disease.[90]​​​

Caution is warranted when considering maintenance PARP inhibitor therapy for more than 2 years.[19]

Primary options

bevacizumab

OR

olaparib

OR

rucaparib

OR

niraparib

platinum-resistant recurrent or refractory disease

1st line – non-platinum-based chemotherapy regimen or bevacizumab or tamoxifen

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ONGOING
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platinum-resistant recurrent or refractory disease
1st line – 

non-platinum-based chemotherapy regimen or bevacizumab or tamoxifen

Patients with platinum-resistant recurrent disease are defined as those who relapse <6 months following completion of first-line platinum-based chemotherapy.

Patients with platinum-refractory disease are those who progress during first-line platinum-based chemotherapy.

Patients with platinum-resistant recurrent or platinum-refractory disease have limited treatment options. These may include best supportive care, enrolment into a clinical trial, or recurrence therapy. Treatment is considered palliative; therefore, ease of drug administration, dosing schedule, anticipated adverse effects, and performance status should be considered. Additionally, the timing for initiating treatment is variable and depends on patient symptoms and findings on examination, laboratory tests (e.g., molecular analysis to confirm BRCA and homologous recombination DNA repair deficiency status, and to identify other markers that may influence management), and imaging.

There is no universal standard approach to managing patients with platinum-resistant recurrent or platinum-refractory disease. However, depending on patient factors (e.g., performance status, bone marrow reserve, quality of life), any of the following non-platinum agents may be considered: liposomal doxorubicin, topotecan, gemcitabine, paclitaxel, bevacizumab, and etoposide.

Tamoxifen and other anti-oestrogens may also be considered, but clinical studies assessing their efficacy are lacking.[208]

Combining bevacizumab with non-platinum chemotherapy agents can be considered in patients with platinum-resistant recurrent disease. In one phase 3 study, progression-free survival was improved (6.7 months vs. 3.4 months) with bevacizumab combined with non-platinum chemotherapy (e.g., paclitaxel, topotecan, or liposomal doxorubicin [decided by the investigator]) versus chemotherapy alone.[209]

In the setting of recurrent or refractory disease, treatment is continued until there is a complete response, disease progression, or unacceptable toxicity. Generally, progression-free survival and overall survival decrease progressively with each line of therapy.[194]

Primary options

doxorubicin liposomal

or

topotecan

or

paclitaxel

or

gemcitabine

or

etoposide

-- AND --

bevacizumab

OR

doxorubicin liposomal

OR

topotecan

OR

gemcitabine

OR

paclitaxel

OR

etoposide

OR

bevacizumab

OR

tamoxifen

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