Among gynecologic cancers, ovarian cancer is associated with the most deaths and is the fifth most frequent cause of death overall in women.1 In 2023, an estimated 19,710 new cases of ovarian cancer will be diagnosed, and 13,270 deaths from ovarian cancer are anticipated to occur in the United States.2 Ovarian cancer comprises a group of cancers that arise from the tissues of the ovary, of which there are 4 main types: ovarian epithelial cancer, ovarian germ cell tumors, sex cord stromal tumors, and borderline ovarian tumors. Approximately 90% of ovarian cancers are epithelial in origin and 7% are stromal cell tumors.3 Ovarian germ cell tumors are rare.3

Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancers 

Ovarian epithelial cancers, which originate from the ovarian surface epithelium, consist of 5 histologic subtypes4: high-grade and low-grade serous carcinoma, clear cell, endometrioid, and mucinous carcinoma. Primary peritoneal cancer and fallopian tube cancer are similar to ovarian epithelial cancer and are treated in the same manner. Risk factors that may contribute to the development of epithelial ovarian cancers include family history of breast and/or ovarian cancer, older age, inherited genetic mutations (BRCA1 and BRCA2 genes),5

Lynch syndrome, history of endometriosis, history of hormone therapy, high body mass index, and tall height.1 If diagnosed early at localized stages, the survival outlook for women with epithelial ovarian cancer is good (93%).6 However, symptoms of ovarian cancer are often unrecognized in early stages, resulting in 80% of cases being diagnosed at advanced stages.7 The delay in diagnosis often results in poor prognosis, as reflected in a 5-year survival rate of 49%.8 

High-grade serous ovarian carcinoma with solid, pseudo-endometrioid, transitional cell-like (SET) features.
Figure. High-grade serous ovarian carcinoma with solid, pseudo-endometrioid, transitional cell-like (SET) features. Credit: Getty Images.

Symptoms of ovarian epithelial, fallopian tube, or peritoneal cancer include1:

  • Pelvic and abdominal pain
  • Abdominal distention and bloating
  • Feeling full or experiencing difficulty eating
  • Urinary urgency or frequency
  • A lump in the pelvic area
  • Vaginal bleeding
  • Gastrointestinal symptoms such as gas or constipation

Treatment of ovarian epithelial ovarian cancers of all stages consists of aggressive cytoreductive surgery followed by platinum-based chemotherapy, most commonly with cisplatin or carboplatin with paclitaxel. Neoadjuvant chemotherapy is used in some patients with advanced disease. Recurrent ovarian cancers are treated with platinum-containing chemotherapy and/or targeted therapy agents such as bevacizumab and poly(ADP-ribose) polymerase (PARP) inhibitors.1 Maintenance therapy with PARP inhibitors has been shown to significantly delay and possibly even prevent disease relapse in some patients, particularly those with BRCA1 and BRCA2 mutations.3 

Borderline Ovarian Tumors

Borderline ovarian tumors, also known as ovarian low malignant potential tumors, are tumors with pathologic and clinical characteristics that are intermediate between benign and malignant ovarian tumors.9 They affect younger patients and are diagnosed in stage I in 75% of cases.10 Overall prognosis for patients with borderline ovarian tumors is very good, with a 5-year survival rate of 90%.11 However, they may have symptomatic late recurrences.

Symptoms of borderline ovarian tumors are similar to those of ovarian epithelial cancer and include abdominal pain and bloating, vaginal bleeding, and urinary and gastrointestinal symptoms. Surgery with consideration for fertility preservation is the main mode of treatment for borderline ovarian tumors, as radiotherapy and chemotherapy have not been shown to be beneficial. 

Ovarian Germ Cell Tumors

Although rare (2% to 3% of all ovarian cancers), ovarian germ cell tumors are aggressive tumors that affect young adults and adolescents.12 Ovarian germ cell tumors are classified as either benign tumors, the majority of which are dermoid cysts, or primitive malignant germ cell tumors, of which dysgerminoma is the most common in young adults.

Yolk sac tumor is the most common histologic type of ovarian germ cell tumor in pediatric and adolescent patients. More than 95% of US patients with ovarian germ cell tumors are diagnosed at stages I to III, and the 5-year cause-specific survival for patients with stages II to III tumors is more than 90%.13 Five-year survival for patients with advanced metastatic ovarian germ cell tumors is 69%.13

The most common symptoms of ovarian germ cell tumors are abdominal pain with pelvic-abdominal mass and acute abdominal pain from rupture, hemorrhage, or torsion of tumors. Germ cell tumors are highly chemosensitive; following initial fertility-sparing surgery, chemotherapy with bleomycin, etoposide, and cisplatin (BEP) has led to remarkable cure rates of more than >95% for patients with FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stages Ic, II, and III disease12 and is the current standard treatment for ovarian germ cell tumors. 

Ovarian Stromal Tumors 

Ovarian sex cord-stromal tumors are relatively uncommon tumors that account for approximately 5% of all primary malignant ovarian tumors.14 These tumors affect the primitive sex cord and/or stromal cells of the gonads. More than 70% of cases are granulosa cell tumors, followed by Sertoli-Leydig tumors.13 Often, sex cord-stromal tumors are hormonally active, leading to virilization, hirsutism, menstrual changes, and precocious puberty.14

Surgery — with consideration for fertility preservation in children, adolescents, and patients of reproductive age — is the initial treatment, followed by platinum-based chemotherapy, most commonly BEP or carboplatin with paclitaxel, for metastatic disease.13 

Treatment of Ovarian Cancer

Treatment of ovarian cancer consists of aggressive debulking surgery, which may involve removal of the ovaries, fallopian tubes, uterus, lymph nodes, and affected tissues in the surrounding area, followed by chemotherapy, often with a combination consisting of a platinum-based compound and a taxane.

More recently, identification of tumor cell biomarkers has led to the development of effective targeted therapy agents in the treatment of ovarian cancer. Multiple factors inform treatment decisions: the type and stage of the tumor, the biomarker status of the tumor, the age of the patient, the need for fertility preservation, and potential side effects. 

Pharmacologic Treatment of Ovarian Cancer

Pharmacologic treatment of ovarian cancer consists of a platinum-based chemotherapy regimen used in neoadjuvant, adjuvant, and maintenance settings, and targeted therapies with molecular agents promoting cancer cell death. 

Chemotherapy

Platinum-based agents are the foundation of chemotherapy regimens used for the treatment of ovarian cancer. Standard induction chemotherapy uses a combination of cisplatin or carboplatin with paclitaxel.

Cisplatin. Cisplatin is a platinum-based chemotherapy agent that induces apoptosis (cell death) in cancer cells by causing damage in their DNA. Cisplatin is approved by the US Food and Drug Administration (FDA) for use as combination treatment of metastatic ovarian tumors in patients who have undergone surgery and/or radiation therapy. As a single agent, cisplatin is used as a secondary therapy in patients with metastatic ovarian tumors that did have not responded to standard chemotherapy and who have not received cisplatin previously.15 

Cisplatin is given intravenously at 75 to 100 mg/m2 per cycle every 3 to 4 weeks on day 1, followed by an intravenous dose of 600 mg/m2 cyclophosphamide every 4 weeks. In patients with residual disease after initial chemotherapy, intraperitoneal delivery of cisplatin has been shown to improve survival, albeit with greater toxicity.1 

Serious side effects reported with cisplatin use for ovarian cancer include15: 

  • Severe nephrotoxicity 
  • Myelosuppression
  • Ototoxicity
  • Anaphylactic-like reactions 
  • Facial edema 
  • Bronchoconstriction
  • Hypotension 

The most common side effects associated with cisplatin are nausea and vomiting.15

Because cisplatin can cause cumulative kidney toxicity and hearing damage, use of nephrotoxic and ototoxic drugs should be avoided during treatment with cisplatin. 

The pregnancy status of female patients with ovarian cancer should be checked before initiating treatment with cisplatin. Female patients should be warned of the risk of fetal harm and advised to use effective contraception during treatment and for 14 months following the completion of treatment. Contraception should be used by male patients with female partners of reproductive potential during treatment and for 11 months after the treatment has been discontinued. Use of cisplatin has been associated with impaired fertility in both women and men. Breastfeeding should be discontinued during treatment.

Carboplatin. Carboplatin is a platinum-based compound that is a component of the standard chemotherapy regimen used for the treatment of ovarian cancer.17 A derivative of cisplatin, carboplatin is often used in place of cisplatin to treat advanced ovarian cancer due to its less toxic profile.16 Carboplatin is used in combination with other chemotherapy agents, including cyclophosphamide. It is also used as a palliative treatment for recurrent ovarian cancer after prior chemotherapy, including cisplatin.17 

Carboplatin is administered intravenously at 360 mg/m2 every 4 weeks as a single agent or at 300 mg/m2 in combination with 600 mg/m2 cyclophosphamide every 4 weeks. 

Bone marrow suppression has been reported with carboplatin treatment; this may require a reduction in dosage. 

The most common side effects associated with carboplatin for ovarian cancer are17:

  • Nausea
  • Vomiting
  • Leukopenia
  • Neutropenia
  • Anemia
  • Magnesium loss
  • Thrombocytopenia 

Pregnant patients should be warned of the risk of potential harm to the fetus with carboplatin treatment, and female patients of reproductive potential should use contraception during treatment. Breastfeeding should be discontinued during treatment with carboplatin. 

Doxorubicin hydrochloride. Doxorubicin hydrochloride is a topoisomerase II inhibitor that inhibits cancer cell growth by damaging their DNA and preventing replication. It is used for the treatment of metastatic ovarian cancer that has progressed or recurred after platinum-based chemotherapy.18 

Doxorubicin hydrochloride is given as an intravenous infusion at 50 mg/m2 over 60 minutes every 4 weeks until disease progression or unacceptable toxicity. 

Severe adverse reactions reported with doxorubicin hydrochloride use for metastatic ovarian cancer include18:

  • Myocardial damage, including congestive heart failure 
  • Serious infusion-related reactions 
  • Palmar-planter erythrodysesthesia (hand-foot syndrome)
  • Neutropenia 
  • Thrombocytopenia 

The most common side effects associated with doxorubicin hydrochloride treatment are18:

  • Hand-foot syndrome
  • Nausea
  • Stomatitis (oral mucositis)
  • Vomiting
  • Rash 

A patient’s pregnancy status should be verified before starting treatment with doxorubicin. Pregnant patients should be advised of the potential risk to the fetus, and women and men of reproductive potential should use effective contraception during and for 6 months following doxorubicin treatment. Use of doxorubicin has been associated with fertility complications in both women and men. 

Gemcitabine. Gemcitabine is a nucleoside metabolic inhibitor that targets tumors by preventing DNA synthesis necessary for cancer cell growth. Gemcitabine is used in combination with carboplatin for the treatment of advanced ovarian cancer that has relapsed at least 6 months after platinum-based chemotherapy.19 

Gemcitabine is administered as an intravenous infusion at 1000 mg/m2 over 30 minutes on days 1 and 8 of each 21-day cycle, in combination with carboplatin area under the curve (AUC) 4 given intravenously on day 1 after gemcitabine administration. 

Severe adverse reactions reported with the use of gemcitabine for ovarian cancer include19:

  • Myelosuppression 
  • Thrombotic microangiopathy 
  • Liver injury 
  • Pulmonary toxicity 
  • Hemolytic uremic syndrome 
  • Renal failure 

The most common side effects associated with gemcitabine are19: 

  • Nausea and vomiting 
  • Anemia 
  • Elevated liver function tests 
  • Neutropenia 
  • Pain 
  • Proteinuria 
  • Fever 
  • Hematuria 
  • Rash 
  • Thrombocytopenia 

Pregnant patients undergoing treatment with gemcitabine should be warned of the risk of fetal harm, and female patients should use contraception during treatment and for 6 months after the final dose. Male patients with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the treatment. Breastfeeding should be discontinued during treatment and for 1 week after the last dose.  

Paclitaxel. Paclitaxel is an antimicrotubule agent that disrupts microtubule reorganization during the cell cycle, leading to cancer cell death. Paclitaxel is approved for the treatment of advanced ovarian cancer. It is used in combination with cisplatin as first-line therapy or as a single agent in patients who have already received other treatment.20 

For previously untreated patients, paclitaxel is administered intravenously at 175 mg/m2 over 3 hours every 3 weeks or at 135 mg/m2 over 24 hours every 3 weeks, followed by cisplatin. For patients with previously treated ovarian cancer, 135 to 175 mg/m2 is given intravenously over 3 hours every 3 weeks. 

To prevent hypersensitivity reactions, patients undergoing treatment with paclitaxel should be pretreated with a corticosteroid, diphenhydramine, and H2 blockers. Paclitaxel should only be used for patients with baseline neutrophil ≥1500/mm3 and platelet counts ≥100,000/mm3. 

Severe adverse reactions reported with the use of paclitaxel for ovarian cancer include20:

  • Fatal anaphylaxis 
  • Severe hypersensitivity reactions
  • Hypotension
  • Dyspnea
  • Angioedema
  • Urticaria 

Due to the increase in risk of cardiac dysfunction, paclitaxel should not be taken with trastuzumab or anthracyclines. Common side effects associated with the administration of paclitaxel include neutropenia, alopecia, anemia, arthralgia, myalgia, diarrhea, leukopenia, nausea and vomiting, infections, peripheral neuropathy, thrombocytopenia, and mucositis.20   

The pregnancy status of female patients should be verified prior to initiation of treatment with paclitaxel, and pregnant patients should be warned of the risk of potential harm to the fetus. Female patients of reproductive potential and male patients with female partners of reproductive potential should use effective contraception during treatment and for 6 months and 3 months, respectively, after treatment.

Topotecan. Topotecan is a topoisomerase I inhibitor that targets cancer cells for cell death by inducing breaks in the DNA. It is indicated for the treatment of metastatic ovarian cancer with disease progression during or after other chemotherapy.21 

Topotecan is administered intravenously at 1.5 mg/m2 for 30 minutes daily for 5 consecutive days, starting on day 1 of a 21-day cycle. 

Topotecan should only be used for patients with baseline neutrophil ≥1500/mm3 and platelet counts ≥100,000/mm3. 

Severe adverse reactions reported with the use of topotecan for ovarian cancer include21:

  • Severe myelosuppression
  • Interstitial lung disease
  • Extravasation
  • Tissue injury 

The most common side effects associated with topotecan are21:

  • Neutropenia
  • Anemia
  • Thrombocytopenia
  • Sepsis
  • Nausea

The pregnancy status of female patients should be verified before treatment, and pregnant patients should be warned of the risk of fetal harm with topotecan treatment. Effective contraception should be used during treatment with topotecan and for 6 months following treatment completion for female patients and for 3 months following completion of treatment for male patients with female partners of reproductive potential. Topotecan may impair fertility in women and men. Breastfeeding should be discontinued during and for 1 week after the treatment.   

Bleomycin, Etoposide, and Cisplatin (BEP).  The BEP protocol is a chemotherapy regimen indicated for the treatment of ovarian germ cell and stromal tumors, and it is the most common first-line protocol for adjuvant therapy for ovarian germ cell tumors.22 BEP has been shown to result in high cure rates in most patients with ovarian germ cell tumors, and it has become the preferred regimen over vincristine, dactinomycin, and cyclophosphamide (VAC), an earlier protocol for the treatment of germ cell tumors.12 

BEP for ovarian cancer is administered as follows23: 

  • Bleomycin 30 units intravenously over 10 minutes, once per week
  • Etoposide 100 mg/m2 intravenously over 60 minutes, daily on days 1 to 5 
  • Cisplatin 20 mg/m2 intravenously over 60 minutes, daily on days 1 to 5
  • Repeat above every 21 days for 3 to 4 cycles 

Despite being very effective, the BEP protocol may cause significant short-term and long-term toxicities in up to 30% of patients.13 Etoposide, a critical component of the BEP regimen, is associated with the development of acute myelogenous leukemia.12 

Severe adverse reactions reported with the use of the BEP regimen for ovarian cancer include the following24:

  • Cisplatin-induced ototoxicity
  • Nephrotoxicity
  • Peripheral neuropathy
  • Bleomycin-associated pulmonary toxicity
  • Myelosuppression
  • Cardiomyopathy
  • Potentially fatal secondary malignancies 

Targeted Therapy

Although cytoreductive surgery followed by chemotherapy have been the mainstream treatment modalities for ovarian cancer, development of drug resistance and chemotherapy-induced toxicities have underscored the need for a more targeted approach for managing this disease. The introduction of targeted therapy agents, bevacizumab, and PARP inhibitors has led to improvements in survival and reduction in toxicity. 

Bevacizumab. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) receptors. VEGF receptor inhibitors target tumors for cell death by inhibiting angiogenesis necessary for tumor growth.25-28 

Bevacizumab is indicated for first-line treatment of ovarian cancer, both during induction and as consolidation therapy. Bevacizumab is used in combination with paclitaxel, liposomal doxorubicin, or topotecan for platinum-resistant recurrent ovarian epithelial cancer in patients who have undergone up to 2 types of chemotherapy. 

Bevacizumab is given intravenously at 10 mg/kg every 2 weeks in combination with one of the following chemotherapy agents: paclitaxel, liposomal doxorubicin, or topotecan administered weekly. Alternatively, bevacizumab may be given at 15 mg/kg every 3 weeks in combination with topotecan every 3 weeks. 

In patients with platinum-sensitive recurrent ovarian epithelial cancer, bevacizumab26-28 is used in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by bevacizumab alone. It is administered intravenously at 15 mg/kg every 3 weeks in combination with carboplatin and paclitaxel for 6 to 8 cycles, or at 15 mg/kg every 3 weeks in combination with carboplatin and gemcitabine for 6 to 10 cycles, followed by bevacizumab as a single agent at 15 mg/kg every 3 weeks until disease progression. 

In patients with stages III-IV or recurrent cancer, bevacizumab26-28 is given after surgery in combination with carboplatin and paclitaxel, followed by bevacizumab alone. Bevacizumab is given intravenously at 15 mg/kg every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by bevacizumab alone at 15 mg/kg for a maximum of 22 cycles or until disease progression. 

Severe adverse reactions reported with bevacizumab treatment for ovarian cancer include25-28:

  • Serious arterial thromboembolic events 
  • Hemorrhagic events
  • Wound healing complications
  • Gastrointestinal perforation
  • Fistula formation

The most common side effects associated with bevacizumab include25-28:

  • Fatigue
  • Nausea
  • Hypertension
  • Nosebleed
  • Diarrhea
  • Headache
  • Neutropenia
  • Peripheral sensory neuropathy
  • Mucosal inflammation 

Pregnant patients undergoing treatment with bevacizumab should be warned of the risk of fetal harm, and effective contraception should be used during treatment and for 6 months after the last dose of bevacizumab. Breastfeeding should be discontinued during and for 6 months after treatment. 

PARP Inhibitors

The development of PARP inhibitors as a therapeutic tool for targeting tumors in patients with homologous recombination deficiency (HRD), which is associated with germline BRCA mutations, has led to significant progress in the treatment of advanced ovarian cancer.29 Inhibition of PARP-mediated repair of single-strand DNA breaks found in BRCA-deficient or BRCA-mutant tumor cells leads to generation of double-strand breaks. The double-strand DNA breaks cannot be repaired in HRD cells, marking them for cell death. Owing to its inability to repair genomic instability, HRD-positive tumors are more sensitive to platinum therapy and thus have a more favorable prognosis.

Olaparib. In 2014, olaparib became the first PARP inhibitor to receive FDA approval for the treatment of advanced ovarian cancer in patients with deleterious or suspected deleterious germline BRCA mutations who had been treated with 3 or more prior lines of chemotherapy.30 

In 2017, based on the results of the SOLO-2 (ClinicalTrials.gov Identifier: NCT01874353) and Study 19 (ClinicalTrials.gov Identifier: NCT00753545) trials that showed significant improvements in progression-free survival (PFS), olaparib was approved for use as maintenance treatment for recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy.30 The recommended tablet dosage of olaparib is 300 mg taken orally twice a day.

Olaparib is also indicated as first-line maintenance treatment of patients with newly diagnosed, BRCA-mutated, advanced ovarian, fallopian tube, or primary peritoneal cancer with germline or somatic mutations in the BRCA1 or BRCA2 gene who demonstrate complete or partial response to platinum-based chemotherapy. The recommended tablet dosage of olaparib is 300 mg taken orally twice a day, until disease progression, unacceptable toxicity, or 2 years of treatment, at which point treatment can be stopped for patients with complete response.31 

Olaparib is also used in combination with bevacizumab as first-line maintenance treatment for patients with advanced ovarian cancer with genomic instability and/or germline or somatic mutations in the BRCA1 or BRCA2 gene who demonstrate complete or partial response to first-line platinum-based chemotherapy. The recommended treatment is 300 mg olaparib taken orally twice a day and bevacizumab administered intravenously at 15 mg/kg every 3 weeks for 15 months (including with chemotherapy and as maintenance treatment).31

Severe adverse reactions reported with olaparib use include31:

  • Pneumonitis
  • Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) 

Common side effects associated with olaparib include31:

  • Anemia
  • Nausea
  • Fatigue
  • Vomiting
  • Diarrhea
  • Neutropenia
  • Leukopenia
  • Headache 

Cumulative myelosuppressive toxicity has been reported with the use of olaparib with other myelosuppressive anticancer agents; therefore, such treatment should be avoided. Using olaparib with other CYP3A4 inhibitors may increase exposure to olaparib. CYP3A4 inducers may decrease the serum concentration of olaparib, thereby decreasing its efficacy. Concomitant use of olaparib with CYP3A4 inhibitors or inducers should be avoided, and the olaparib dose should be adjusted if the agents are taken together.

The pregnancy status of female patients should be verified before initiation of olaparib treatment, and pregnant patients should be warned of risk of harm to the fetus. Female patients of reproductive potential should use effective contraception to avoid pregnancy during and for at least 6 months after olaparib treatment. Male patients and their female partners of reproductive potential should use effective contraception during treatment and for 3 months afterward. Male patients should not donate sperm during and for 3 months after treatment. Breastfeeding should be discontinued during treatment and for 1 month after the last dose. 

Niraparib. Niraparib is a highly selective PARP-1 and PARP-2 inhibitor. It was approved by the FDA in 2017 for maintenance treatment of recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancers in patients with complete or partial response to platinum-based chemotherapy.30 Niraparib is also approved as maintenance treatment for advanced ovarian cancer in patients with HRD, specifically a deleterious or suspected deleterious BRCA mutation or genomic instability, who were treated with 3 or more prior chemotherapy regimens. In 2020, niraparib was approved for maintenance treatment of advanced ovarian cancer in patients who are in complete or partial response to first-line platinum chemotherapy.30 

For recurrent ovarian cancer, treatment with niraparib should begin within 8 weeks since the most recent platinum-based therapy, with the recommended dosage of 300 mg orally every day. For advanced ovarian cancer, treatment should begin within 12 weeks from the most recent platinum-based therapy, with 200 to 300 mg orally every day, with the dose depending on the patient’s weight and platelet count.32 

Severe adverse reactions reported with the use of niraparib for ovarian cancer include32:

  • Bone marrow suppression 
  • Hypertension 
  • MDS/AML
  • Posterior reversible encephalopathy syndrome (PRES) 

Common side effects associated with niraparib include32:

  • Nausea 
  • Thrombocytopenia 
  • Fatigue 
  • Anemia 
  • Constipation 
  • Musculoskeletal pain
  • Vomiting 
  • Abdominal pain and distension 
  • Neutropenia 

Due to the potential for fetal harm, the pregnancy status of female patients should be checked prior to treatment with niraparib. Female patients of reproductive potential should use effective contraception during treatment and for 6 months following the final dose. Breastfeeding should be discontinued during treatment and for 1 month after treatment. 

Rucaparib. Rucaparib is another PARP inhibitor approved to treat patients with ovarian epithelial, fallopian tube, or primary peritoneal cancer. It was approved by the FDA in 2018 as a single-agent maintenance therapy in patients with recurrent cancer who experienced complete or partial response to platinum-based chemotherapy, based on results demonstrating improved PFS with rucaparib treatment in patients with BRCA mutations and HRD.30 

The recommended dosage of rucaparib is 600 mg taken orally twice daily until disease progression or unacceptable toxicity.33 

The development of MDS/AML has been reported with the use of rucaparib. 

Common side effects associated with rucaparib include33:

  • Increased creatinine 
  • Decreased hemoglobin 
  • Increased cholesterol 
  • Nausea 
  • Fatigue 
  • Liver damage 
  • Abdominal pain or distension 
  • Decreased platelets and leukocytes 
  • Rash 
  • Anemia 
  • Constipation 
  • Vomiting
  • Diarrhea 

Patients should avoid taking medications containing CYP1A2, CYP3A, CYP2C9, and CYP2C19 substrates such as warfarin while undergoing treatment with rucaparib. If unavoidable, dose adjustment should be implemented to avoid serious adverse reactions. 

The pregnancy status of female patients should be verified prior to initiating treatment with rucaparib. Due to potential harm to the fetus, effective contraception should be used by female patients of reproductive potential during treatment and for 6 months following the last dose. Male patients with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the treatment. Donating sperm should be avoided during that time. Breastfeeding should be avoided during treatment and for 2 weeks following the last dose. 

Folate Receptor-Alpha-Targeting Drugs

Up to 90% of primary and recurrent ovarian tumors have been reported to have overexpression of folate receptor-alpha (FRα), a cell surface glycoprotein that transports folate into cells to enable DNA synthesis and cell growth.34 Overexpression of FRα in a large majority of ovarian tumor cells, particularly in patients with platinum-resistant disease, makes it an ideal therapeutic target in the treatment of ovarian cancer. 

Mirvetuximab soravtansine-gynx. Approved by the FDA in 2022 under the Accelerated Approval Program,35 mirvetuximab soravtansine-gynx is an antibody-drug conjugate made with an antibody to FRα linked to maytansinoid DM4, a tubulin polymerization inhibitor. In the single-arm, phase 2 SORAYA trial (ClinicalTrials.gov Identifier: NCT04296890), mirvetuximab soravtansine-gynx was shown to have an overall response rate (ORR) of 32.4%.36 It is used in the treatment of patients with FRα-positive, platinum-resistant ovarian epithelial, fallopian tube, or primary peritoneal cancer who have received 1 to 3 types of systemic therapy. 

Mirvetuximab soravtansine-gynx is given intravenously at 6 mg/kg of adjusted ideal body weight every 3 weeks, in a 21 day-cycle, and continued until progression or unacceptable toxicity.37 

Severe adverse reactions reported with mirvetuximab soravtansine-gynx use include37:

  • Severe ocular toxicities
  • Keratopathy
  • Visual impairment
  • Photophobia
  • Dry eye
  • Eye pain 
  • Uveitis 

Common side effects associated with the use of mirvetuximab soravtansine-gynx include37: 

  • Vision impairment
  • Liver damage
  • Fatigue
  • Nausea
  • Keratopathy
  • Decreased lymphocytes
  • Peripheral neuropathy
  • Diarrhea
  • Eye pain 

Use of strong CYP3A4 inhibitors should be avoided in patients undergoing treatment with mirvetuximab soravtansine-gynx as the combination may increase exposure to DM4 and subsequently increase the risk of adverse reactions. 

The pregnancy status of female patients of reproductive potential should be checked prior to starting treatment with mirvetuximab soravtansine-gynx. Pregnant patients should be advised of potential harm to the fetus, and effective contraception should be used during treatment and for 7 months following the last dose to avoid pregnancy. Breastfeeding should be discontinued during treatment and for 1 month following treatment. 

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Author Bio

Bora Lee, PhD earned a Bachelor of Science in biology from Boston College and a PhD in Molecular and Cellular Biology from the University of Massachusetts Amherst. She has more than 10 years of translational research experience in reproductive medicine and women’s health, with a focus on fertility and placental health. She is passionate about improving people’s lives by helping them to make informed health decisions.

Topics:

Ovarian Cancer Treatment Regimens