Overview of Ovarian Cancer Treatment

Epithelial ovarian cancer treatment centers on platinum-based chemotherapy with targeted maintenance strategies. PARP inhibitors (olaparib, niraparib, rucaparib) have transformed maintenance therapy, particularly for BRCA-mutated and homologous recombination deficient (HRD) disease. Bevacizumab remains an important component of frontline and maintenance regimens. Mirvetuximab soravtansine provides a new option for FRΞ±-positive, platinum-resistant disease.

Treatment Approach by Setting

First-Line Maintenance Therapy

  • Olaparib (BRCA-mutated, SOLO-1)
  • Niraparib (all-comers, PRIMA)
  • Bevacizumab Β± olaparib (PAOLA-1)

Platinum-Sensitive Recurrence

  • Platinum-based rechallenge + PARP inhibitor maintenance
  • Olaparib, niraparib, or rucaparib as maintenance

Platinum-Resistant Disease

  • Mirvetuximab soravtansine (Elahere) for FRΞ±-positive
  • Bevacizumab + chemotherapy
  • Single-agent chemotherapy (topotecan, PLD, gemcitabine)

Epidemiology & Impact

Ovarian cancer is the fifth leading cause of cancer death in US women with approximately 19,680 new cases and 12,740 deaths in 2025. About 60% present with advanced disease due to lack of effective screening. HGSC is the most common subtype (70%). BRCA1/2 mutations confer 20-40% lifetime risk. All patients should receive germline and somatic genetic testing.

Molecular Biology & Biomarkers

HGSC has near-universal TP53 mutations (96%) and homologous recombination deficiency in approximately 50%. BRCA1/2 mutations (25%) predict PARP inhibitor and platinum sensitivity. HRD testing identifies broader populations for PARP inhibitor benefit. Other subtypes have distinct profiles: clear cell (ARID1A, PIK3CA), endometrioid (CTNNB1, PTEN).

Evolving Treatment Landscape

PARP inhibitors have transformed treatment. Olaparib maintenance improved OS in BRCA-mutated HGSC (SOLO-1: 7-year OS 67% vs 47%). Niraparib benefits HRD-positive populations. Bevacizumab is important in first-line and maintenance. Standard chemotherapy is carboplatin-paclitaxel. Mirvetuximab soravtansine targets FRalpha in platinum-resistant disease.

Approved Therapies

Avastin
bevacizumab
FDA 2018Genentech
Indication: Stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection, in combination with carboplatin and paclitaxel, followed by bevacizumab as a single agent
Dosing: 15 mg/kg IV every 3 weeks for up to 22 cycles (in combination with chemotherapy for cycles 2-6, then as single agent for cycles 7-22)
Trial: NCT00262847 β†— (GOG-0218)
Lynparza
olaparib
FDA 2014AstraZeneca
Indication: Deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy; Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy; First-line maintenance treatment with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to first-line platinum-based chemotherapy
Dosing: 300 mg orally twice daily for monotherapy; 300 mg twice daily (in combination with bevacizumab 15 mg/kg IV every 3 weeks) for first-line maintenance
Trial: NCT01874353 β†— (SOLO-1)
Key Publication: Moore et al. NEJM 2018 β†—
Rubraca
rucaparib
FDA 2016Clovis Oncology
Indication: Deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with 2 or more chemotherapies; Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
Dosing: 600 mg orally twice daily
Trial: NCT01968213 β†— (ARIEL3)
Key Publication: Coleman et al. Lancet 2017 (ARIEL3) β†—
Zejula
niraparib
FDA 2017GSK
Indication: Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy; First-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy
Dosing: Individualized based on body weight and platelet count: 200 mg or 300 mg orally once daily
Trial: NCT01847274 β†— (NOVA)
Elahere
mirvetuximab soravtansine-gynx
FDA 2022ImmunoGen
Indication: Adult patients with folate receptor alpha (FRΞ±) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior systemic treatment regimens
Dosing: 6 mg/kg (adjusted ideal body weight) IV on day 1 of a 21-day cycle until disease progression or unacceptable toxicity
Trial: NCT04296890 β†— (SORAYA)

Treatment Strategies

First-Line Maintenance Therapy

For patients achieving response to frontline platinum-based chemotherapy, maintenance therapy options include:

  • BRCA-mutated: Olaparib monotherapy (preferred) or niraparib
  • HRD-positive: Olaparib + bevacizumab or niraparib
  • HRD-negative: Bevacizumab monotherapy

Platinum-Sensitive Recurrence

Platinum-based chemotherapy followed by maintenance PARP inhibitor (olaparib, niraparib, or rucaparib) for responders. PARP inhibitors provide significant PFS benefit in platinum-sensitive recurrent disease, particularly for BRCA-mutated patients.

Platinum-Resistant Disease

Treatment options include single-agent chemotherapy (paclitaxel, topotecan, pegylated liposomal doxorubicin) or the FRΞ±-targeting antibody-drug conjugate mirvetuximab soravtansine for FRΞ±-positive tumors. FRΞ± testing should be performed for all platinum-resistant patients.