Understanding Recurrent or Progressive Ovarian Cancer

The Basics

Most patients with advanced disease (diagnosed at stage III or IV) have no disease remaining after completing surgery and chemotherapy that includes platinum (usually carboplatin or cisplatin). Unfortunately, despite initial response to treatment, many will see their disease recur. Some women will not have their cancer eliminated by the first-line treatment.

Recurrence happens because chemotherapy may not eliminate all of the cancer cells (they are too small to be visible on a scan). Those remaining cells are either resistant to the initial treatment or are not growing during treatment. Only growing cells can be killed by chemotherapy. Those cancer cells can continue to divide and ultimately form new tumors, which can happen months or years after treatment.

Therapeutic choices after recurrence are complex. Many factors, such as how much time has passed since treatment with platinum and which drugs were given after that, come into play.

Platinum status is important since it predicts the likelihood that re-treatment with platinum will be effective and influences choice of subsequent treatment.

A platinum-sensitive recurrence occurs more than six months after ending treatment with platinum. Re-treatment with a combination of platinum and another drug is often beneficial.
A platinum-resistant recurrence occurs less than six months after the last platinum treatment. Non-platinum drugs are prescribed to treat it.
Platinum refractory cancer continues to grow while on treatment. Non-platinum drugs are prescribed to treat it.

In addition to standard chemotherapy, there are new drugs in various stages of clinical development that can sometimes be better options. Some of these have clinical results available.

There are many approved and investigational drugs (agents in clinical trials) from which to choose. This is where understanding the genomic changes in a tumor can make an enormous difference. Some of these mutations can have a direct bearing on which treatments will be the most appropriate for a patient’s unique cancer. Information from a Tumor Blueprint can be helpful in making these decisions.

Treatments for Platinum-Sensitive Recurrence

These tables list the drugs most commonly used to treat cancer that has come back more than six months after the last platinum treatment. Groups of drugs are used in combination. These drugs are listed in the National Comprehensive Cancer Network (NCCN) guidelines as standard treatment options.

Standard of Care for Platinum-Sensitive Recurrence

Drug(s)	Clinical Notes
Carboplatin or Cisplatin	Standard of care is Carboplatin or Cisplatin combined with Gemzar, Doxil or Taxol. Adding Avastin to platinum-based chemo can increase the time before cancer comes back or gets worse. To see how effective these drugs are, click here. To see side effects for these drugs, click here. To see prescribing information, click here.
Carboplatin or Cisplatin Gemcitabine (Gemzar) Bevacizumab (Avastin)
Carboplatin or Cisplatin Paclitaxel (Taxol) Bevacizumab (Avastin)
Carboplatin or Cisplatin Liposomal doxorubicin (Doxil)

Treatments for BRCA-positive* Patients

*BRCA-positive patients have a mutation in the BRCA1 or BRCA2 gene detected in their blood (germline mutation) or tumor (somatic mutation)
Drug(s)	Clinical Notes
Olaparib (Lynparza)	PARP inhibitors (Lynparza and Rubraca) may be just as effective as standard chemo in BRCA-positive* patients who have recurred more than one time. To see how effective these drugs are, click here. To see side effects for these drugs, click here. To see prescribing information, click here for olaparib or click here for rucaparib.
Rucaparib (Rubraca)

Promising Drugs in Clinical Development for Platinum-Sensitive Recurrence

*BRCA-positive patients have a mutation in the BRCA1 or BRCA2 gene detected in their blood (germline mutation) or tumor (somatic mutation)
Drug(s)	Trial Phase	Clinical Notes
Olaparib (Lynparza) Cediranib	III (results pending)	For patients that are not BRCA-positive*, adding Cediranib to Lynparza may make the treatment as effective as standard chemo To see detailed Phase II results, click here.
Carboplatin Paclitaxel (Taxol) Farletuzumab	II (results pending)	Adding this folate receptor-targeted antibody to chemo increased time until cancer comes back in women with low CA125 To see detailed Phase III results, click here.
Durvalumab (Imfinzi) Olaparib (Lynparza)	II	For BRCA-positive patients, the combination of immune checkpoint inhibitor (Imfinzi) with PARP inhibitor (Lynparza) may be as effective as platinum-based chemotherapy To see detailed Phase II results, click here. For ongoing trials with these drugs, click here.

There are drugs in earlier stages of development that already have results. Visit the Trial Results page to see those.

There are other drugs, including PARP inhibitor combinations and immunotherapies, being evaluated in clinical trials for treatment of platinum-sensitive recurrent ovarian cancer. Visit the clinical trials page and scroll down to see them.

Treatments for Platinum-Resistant or Refractory Recurrence

These tables list the drugs most commonly used for treating cancer has progressed on treatment (ie., refractory) or has come back less than 6 months after the last platinum treatment (ie., resistant). Groups of drugs are used in combination. These drugs are listed in the National Comprehensive Cancer Network (NCCN) guidelines as standard treatment options.

Standard of Care for Platinum-Resistant or Refractory Recurrence

Drug(s)	Clinical Notes
Paclitaxel (Taxol) Bevacizumab (Avastin)	Standard of care is treatment with single agent Taxol, Doxil, Topotecan or Gemzar. Adding Avastin can increase the time before the cancer comes back or gets worse. To see clinical trial results for these drugs, click here. To see side effects for these drugs, click here. To see prescribing information, click here.
Liposomal Doxorubicin (Doxil) Bevacizumab (Avastin)
Topotecan (Hycamtin) Bevacizumab (Avastin)
Gemcitabine (Gemzar)
Bevacizumab (Avastin)	Taking Avastin can decrease fluid build-up in the abdominal or peritoneal cavity (called ascites). To see how effective this drug is, click here.

Treatment for BRCA-positive* Patients

*BRCA-positive patients have a mutation in the BRCA1 or BRCA2 gene detected in their blood (germline mutation) or tumor (somatic mutation)
Drug(s)	Clinical Notes
Olaparib (Lynparza)	PARP inhibitors (Lynparza and Rubraca) may be just as effective as standard chemo in BRCA-positive* patients who have recurred more than one time. To see how effective these drugs are, click here. To see side effects for these drugs, click here. To see prescribing information, click here for olaparib or click here for rucaparib.
Rucaparib (Rubraca)

Promising Drugs in Clinical Development for Platinum-Resistant Recurrence

*BRCA-positive patients have a mutation in the BRCA1 or BRCA2 gene detected in their blood (germline mutation) or tumor (somatic mutation)
Drug(s)	Trial Phase	Clinical Notes
Mirvetuximab Soravtansine (IMGN853)	III (results pending)	Folate receptor-targeted antibody + cytotoxic drug conjugate (ADC) may be as effective as chemotherapy + Avastin To see detailed Phase I results, click here. For ongoing trials with this drug, click here.
Prexasertib	II	Chk1/2 inhibitor may be more effective than standard chemo To see detailed Phase II results, click here. For ongoing trials with this drug, click here.
Niraparib (Zejula) Pembrolizumab (Keytruda)	II	Patients that are not BRCA-positive* may benefit from PARP inhibitors (Zejula) if immunotherapy (Keytruda) is added To see detailed Phase II results, click here. For ongoing trials with these or similar drugs, click here.

There are drugs in earlier stages of development that already have results. Visit the Trial Results page to see those.

There are other drugs being evaluated in clinical trials for treatment of platinum-resistant recurrent ovarian cancer. Visit the clinical trials page and scroll down to see them.