Ovarian cancer

Evidence chains

A lane follows one defined population and setting, where each new trial tests against what was then standard. Compare only within a lane, and read every comparison as illustrative.

First-line chemotherapy: regimens and schedules

Adults with newly diagnosed advanced epithelial ovarian, fallopian tube or primary peritoneal cancer given platinum-based first-line chemotherapy in randomised comparisons of drugs or schedules (GOG-111, OV-10, ICON3, GOG-158, AGO-OVAR-3, JGOG 3016, GOG-262, ICON8) · Locally advanced · endpoint: PFS

First-line intraperitoneal versus intravenous chemotherapy

Adults with newly diagnosed optimally debulked ovarian cancer: GOG-172 enrolled stage III disease with no residual mass over 1 cm; GOG-252 enrolled advanced disease designed for residual disease of 1 cm or less · Locally advanced · endpoint: PFS

First-line chemotherapy with an added agent (bevacizumab or atezolizumab)

Adults with newly diagnosed advanced epithelial ovarian, fallopian tube or primary peritoneal cancer given first-line carboplatin and paclitaxel with or without an added agent (GOG-218: bevacizumab; IMagyn050: atezolizumab) · Locally advanced · endpoint: PFS

First-line PARP inhibitor maintenance, biomarker-defined populations

Adults with newly diagnosed advanced ovarian cancer in response to first-line platinum-based chemotherapy, in biomarker-defined groups: SOLO-1 BRCA1/2-mutated disease; PRIMA tumours with homologous recombination deficiency (HRD); PAOLA-1 HRD-positive tumours, all treated with bevacizumab · Maintenance · endpoint: PFS

Platinum-sensitive relapse: PARP inhibitor maintenance in BRCA-mutated disease

Adults with platinum-sensitive relapsed ovarian cancer responding to platinum-based chemotherapy, BRCA-mutated groups only: SOLO2 (BRCA1/2 mutation), NOVA (germline BRCA cohort) and ARIEL3 (BRCA-mutant carcinoma) · Maintenance · endpoint: PFS

Platinum-resistant disease: randomised phase 3 trials

Adults with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer in randomised phase 3 trials: AURELIA (no more than two prior regimens), MIRASOL (folate receptor alpha-high, one to three prior lines), ROSELLA (one to three prior lines, all with prior bevacizumab), KEYNOTE-B96 (one to two prior regimens, PD-L1 CPS 1 or more drawn) · Relapsed / refractory · endpoint: PFS

Recurrent low-grade serous carcinoma: MEK inhibitor versus standard treatment

Adults with recurrent low-grade serous carcinoma of the ovary, fallopian tube or peritoneum in randomised trials of a MEK inhibitor against a standard-treatment control (GOG 281: trametinib; MILO: binimetinib) · Relapsed / refractory · endpoint: PFS

Standard of care, then and now

How the usual sequence of treatment changed for one setting. Choose a point in time; each step links to the milestone behind it.

Newly diagnosed advanced disease: maintenance after first-line chemotherapy

Adults with newly diagnosed advanced epithelial ovarian, fallopian tube or primary peritoneal cancer responding to first-line platinum-based chemotherapy · Maintenance

Platinum-resistant disease: systemic treatment

Adults with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer · Relapsed / refractory

Standard of care today

Screening

The US Preventive Services Task Force final recommendation statement of 13 February 2018 (recommendation page and JAMA abstract read) recommends against screening for ovarian cancer in asymptomatic women who are not known to have a high-risk hereditary cancer syndrome (grade D). The page says transvaginal ultrasound and serum CA-125 testing are commonly used to evaluate women with signs or symptoms and have been evaluated in screening studies. The randomised trial evidence (PLCO, UKCTOCS) is summarised in the hooks. No FDA or EMA action on ovarian cancer screening is described here.

US Preventive Services Task Force 2018US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, Barry MJ, Davidson KW, et al 2018Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, et al 2011Menon U, Gentry-Maharaj A, Burnell M, Singh N, Ryan A, Karpinskyj C, et al 2021

Prevention

An ACOG Clinical Practice Update (Obstetrics and Gynecology 2026; abstract read, full text not read) states that it provides updated information supporting complete bilateral salpingectomy at the time of obstetric and gynecologic surgery, and wider availability of salpingectomy during non-gynecologic abdominopelvic surgery, for primary prevention of epithelial ovarian cancer. The cohort evidence for risk-reducing salpingo-oophorectomy and salpingectomy is in the milestone timeline. No FDA or EMA action specific to prevention is described here.

Guideline: American College of Obstetricians & Gynecologists Committee on Clinical Consensus—Gynecology 2026Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, et al 2002Falconer H, Yin L, Grönberg H, Altman D 2015

Any setting

Genetic testing. The ASCO guideline on germline and somatic testing (J Clin Oncol 2020; abstract read, full text not read) states that all women with epithelial ovarian cancer should have germline testing for BRCA1/2 and other ovarian cancer susceptibility genes, with somatic BRCA1/2 testing for those without a germline variant, and testing at the time of diagnosis. The 2025 ASCO neoadjuvant chemotherapy guideline update (abstract read) states that all patients should be offered germline genetic and somatic testing at diagnosis. FDA companion diagnostic approvals were not opened.

Konstantinopoulos PA, Norquist B, Lacchetti C, Armstrong D, Grisham RN, Goodfellow PJ, et al 2020Gaillard S, Lacchetti C, Armstrong DK, Cliby WA, Edelson MI, Garcia AA, et al 2025

Neoadjuvant

Sequencing of surgery and chemotherapy in stage III-IV disease. The 2025 ASCO neoadjuvant chemotherapy guideline update, endorsed by the Society of Gynecologic Oncology (abstract read, full text not read), recommends primary cytoreductive surgery for patients fit for surgery with a high likelihood of complete cytoreduction, and neoadjuvant chemotherapy with a platinum-taxane doublet when complete cytoreduction is unlikely or perioperative risk is high. It states that interval cytoreductive surgery should follow no more than four cycles in patients with response or stable disease, that hyperthermic intraperitoneal chemotherapy may be offered during interval surgery in stage III disease with good performance status and adequate renal function, and that chemotherapy then continues to six cycles with optional bevacizumab. No FDA or EMA action on a surgical strategy is described here.

Gaillard S, Lacchetti C, Armstrong DK, Cliby WA, Edelson MI, Garcia AA, et al 2025

Locally advanced

First-line systemic therapy for stage III-IV disease. FDA approved bevacizumab with carboplatin and paclitaxel, followed by single-agent bevacizumab, for stage III or IV epithelial ovarian, fallopian tube or primary peritoneal cancer following initial surgical resection on 13 June 2018 (supplement approval letter read; it has no accelerated-approval wording, so a regular approval is an inference). The indication is in the Avastin label record read through openFDA (version 39, effective 6 January 2025). The 2025 ASCO guideline abstract names a platinum-taxane doublet and optional bevacizumab after interval surgery.

FDA 2018FDA 2025Gaillard S, Lacchetti C, Armstrong DK, Cliby WA, Edelson MI, Garcia AA, et al 2025

Maintenance

First-line maintenance after response to platinum-based chemotherapy. FDA documents read:

• olaparib for germline or somatic BRCA-mutated disease (19 December 2018) and olaparib with bevacizumab for HRD-positive disease (8 May 2020), both in the Lynparza label record read through openFDA (version 38, effective 10 July 2025)
• niraparib, approved on 29 April 2020 for patients in complete or partial response with no biomarker restriction in the letter, was narrowed to HRD-positive disease by supplement approval letters signed 18 June 2025 (supplements 3 and 4 of the tablet application
• the letter says it provides for an update 'to narrow the indication') and the Zejula label record read through openFDA (version 10, effective 28 July 2026) carries that wording. No FDA first-line rucaparib ovarian indication appears in the letters read or in the Drugs@FDA supplement list for the rucaparib application (2022 onward). The ESMO Express Update of February 2026 (full text read) recommends PARP inhibitor maintenance, with or without bevacizumab, for BRCA1/2-mutated or BRCA1/2 wild-type HRD-positive tumours with response to first-line platinum-paclitaxel [I, A], listing olaparib for 2 years (BRCA1/2-mutated tumours only), olaparib for 2 years with bevacizumab for 15 months, rucaparib for 2 years and niraparib for 3 years among the options, and states that bevacizumab for 15 months, rucaparib or niraparib can be recommended for HRD-negative tumours
• the status of rucaparib for this use outside the United States was not checked. The ASCO PARP inhibitor rapid recommendation update of 2022 (J Clin Oncol, PMID 36150092) is cited by identifier only

FDA 2018FDA 2020FDA 2020FDA 2025FDA 2025FDA 2026Guideline: González-Martín A, Ledermann JA 2026Guideline: Tew WP, Lacchetti C, Kohn EC 2022

Relapsed / refractory

Platinum-sensitive recurrence. FDA approved bevacizumab with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by single-agent bevacizumab, on 6 December 2016 (letter read; the indication is in the Avastin label record). PARP inhibitor maintenance after response to platinum is now worded for BRCA-mutated disease only:

• olaparib (germline or somatic
• supplement 29 letter signed 12 September 2023), niraparib (germline BRCA-mutated
• 8 December 2022 letter) and rucaparib (germline and/or somatic BRCA mutation
• 21 December 2022 letter)
• the current Rubraca label was not retrieved. The later-line single-agent treatment indications were removed in 2022 (see the hooks). The ASCO living guideline on recurrence (version 2026.1.0
• abstract read, full text not read) states that clinicians should offer a platinum-based combination (pegylated liposomal doxorubicin with carboplatin, paclitaxel with carboplatin, or gemcitabine with carboplatin), that bevacizumab may be added with bevacizumab maintenance, that there is insufficient evidence to recommend secondary cytoreduction or HIPEC, and that secondary cytoreduction may be discussed where complete gross resection is highly achievable in platinum-sensitive recurrence. A footnote to the ESMO Express Update's recurrent-disease algorithm lists niraparib and rucaparib 'regardless of BRCA1/2-mut status' beside olaparib for BRCA1/2-mutated disease (the figure itself was not viewed), which differs from the FDA wording

FDA 2016FDA 2025FDA 2023FDA 2022FDA 2022FDA 2025FDA 2026Guideline: Lesnock JL, Temin S, Bouberhan S, Adams SF, Barber EL, Burkett WC, et al 2026Guideline: González-Martín A, Ledermann JA 2026

Relapsed / refractory

Platinum-resistant disease. FDA documents read:

• mirvetuximab soravtansine-gynx for folate receptor alpha-positive disease after one to three prior regimens (accelerated approval, 14 November 2022, 'based on tumor response rate and durability of response'
• the 22 March 2024 supplement approval submitted the MIRASOL study report to satisfy the postmarketing requirement, and the letter states that it fulfils commitments under 21 CFR 601.41 without using the word converted
• FDA's list of cancer accelerated approvals with verified clinical benefit gives 14 November 2022 and 22 March 2024 for this indication)
• pembrolizumab with paclitaxel, with or without bevacizumab, for tumours with PD-L1 CPS 1 or more by an FDA-authorized test after one or two prior regimens (10 February 2026)
• relacorilant with nab-paclitaxel after one to three prior regimens, at least one including bevacizumab (25 March 2026
• no accelerated-approval wording)
• and bevacizumab with paclitaxel, pegylated liposomal doxorubicin or topotecan after no more than two prior regimens (14 November 2014
• a replacement letter corrects wording omitted from the original). The EMA Elahere page states a marketing authorisation issued on 14 November 2024. The ASCO living guideline (abstract read) strongly recommends mirvetuximab soravtansine for high-grade platinum-resistant or platinum-refractory disease with validated folate receptor alpha expression, and lists pegylated liposomal doxorubicin, weekly or three-weekly paclitaxel, bevacizumab with chemotherapy, and relacorilant with nab-paclitaxel as other options
• the ESMO Express Update (full text read) recommends mirvetuximab soravtansine for high-grade serous disease with a platinum-free interval under 6 months, high folate receptor alpha expression (at least 75% of viable tumour cells with 2+ or 3+ staining) and one to three prior systemic lines [I, A]. No guideline text read here addresses pembrolizumab in this setting

FDA 2022FDA 2024US Food and Drug Administration 2026FDA 2026FDA 2026FDA 2014EMA 2026Guideline: Lesnock JL, Temin S, Bouberhan S, Adams SF, Barber EL, Burkett WC, et al 2026Guideline: González-Martín A, Ledermann JA 2026

Relapsed / refractory

Recurrent low-grade serous ovarian cancer. FDA granted accelerated approval to the avutometinib and defactinib co-pack for adults with KRAS-mutated recurrent low-grade serous ovarian cancer who have received prior systemic therapy on 8 May 2025 (letter read; it names RAMP 301 as the confirmatory trial and does not name RAMP 201). The 2026 Mekinist (trametinib) label read has no low-grade serous ovarian cancer indication; the only ovarian mention is a row in its BRAF V600E solid-tumour response table. The ASCO living guideline's stated scope is high-grade serous and endometrioid disease, so its abstract does not address this setting.

FDA 2025FDA 2026Guideline: Lesnock JL, Temin S, Bouberhan S, Adams SF, Barber EL, Burkett WC, et al 2026

Trials to watch

• OVHIPEC-2 NCT03772028

  In stage III epithelial ovarian, fallopian tube or extra-ovarian cancer in people who are candidates for primary cytoreductive surgery, does adding hyperthermic intraperitoneal chemotherapy with cisplatin to primary surgery change overall survival? Registry record: randomised phase 3 with two arms (primary surgery with HIPEC; primary surgery without HIPEC); status active, not recruiting; enrolment 538 (estimated); the single primary outcome listed is overall survival; start 1 January 2020 (actual); estimated primary completion April 2028; no results posted. The design is described in a protocol paper (Int J Gynecol Cancer 2020, PMID 32205449); no efficacy results were found in a PubMed search on 21 October 2026.

• GLORIOSA NCT05445778

  In high-grade serous platinum-sensitive recurrent disease with high folate receptor alpha expression that has not progressed after second-line platinum-based chemotherapy plus bevacizumab, does maintenance mirvetuximab soravtansine with bevacizumab differ in progression-free survival from bevacizumab alone? Registry record: randomised, open-label phase 3; status active, not recruiting; enrolment 520 (actual); the primary outcome listed is progression-free survival; start 15 March 2023 (actual); estimated primary completion April 2027; no results posted. A protocol paper exists (Future Oncol 2024, PMID 39082675); no efficacy results were found in a PubMed search on 21 October 2026.

• RAINFOL-02 NCT06619236

  In platinum-resistant high-grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer after one to four prior lines (prior bevacizumab required where available and suitable), does rinatabart sesutecan (Rina-S) differ in progression-free survival from investigator's-choice chemotherapy? Registry record: randomised, open-label phase 3; participants may be enrolled regardless of folate receptor alpha expression; status active, not recruiting; enrolment 584 (actual); the primary outcome listed is progression-free survival; start 7 February 2025 (actual); primary completion listed as 18 August 2026 (actual); no results posted (registry record last updated 28 September 2026). No publication was found in PubMed on 21 October 2026, and a web search on that date found no announcement of phase 3 results; congress and company reports were not otherwise searched.

• RAMP 301 NCT06072781

  In recurrent low-grade serous ovarian cancer that has progressed after at least one prior systemic therapy with documented KRAS status, does avutometinib plus defactinib differ in progression-free survival from investigator's choice (pegylated liposomal doxorubicin, paclitaxel, letrozole or anastrozole)? Registry record: randomised, open-label phase 3 with crossover; the primary outcome listed is progression-free survival by blinded independent central review; status recruiting; enrolment 270 (estimated); start 18 March 2024 (actual); estimated primary completion October 2028; no results posted. It is the confirmatory trial named in the FDA accelerated approval letter of 8 May 2025. A protocol paper exists (Int J Gynecol Cancer 2025, PMID 39375168); no efficacy results were found in a PubMed search on 21 October 2026.

• NRG-GY036 NCT06580314

  In newly diagnosed stage III or IV BRCA1/2-mutated or HRD-positive ovarian cancer responding to first-line platinum-based chemotherapy, is one year of maintenance olaparib, with or without bevacizumab, non-inferior to two years for progression-free survival (the registry's primary objective is stated as a non-inferiority comparison)? Registry record: randomised phase 3 from NRG Oncology (organisation study ID NRG-GY036), two arms of olaparib for up to 2 years (arm I) or 1 year (arm II) with optional bevacizumab for up to 1 year; the primary outcome listed is progression-free survival at least 360 days after randomisation (PFS360); status recruiting; enrolment 880 (estimated); start 12 March 2025 (actual); estimated primary completion 31 December 2034; no results posted. No publication was found in a PubMed search on 21 October 2026.

• DESTINY-Ovarian01 NCT06819007

  In HER2-expressing (IHC 3+, 2+ or 1+) advanced high-grade epithelial ovarian cancer, does first-line maintenance with trastuzumab deruxtecan plus bevacizumab differ in progression-free survival from bevacizumab alone? Registry record: randomised, open-label phase 3 (ENGOT-ov89 / GOG-3112 and other group identifiers; sponsor study ID DS8201-772); the primary outcome listed is progression-free survival by blinded independent central review in the HER2 IHC 3+/2+ population; status recruiting; enrolment 582 (estimated); start 19 March 2025 (actual); estimated primary completion November 2028; no results posted. No publication was found in a PubMed search on 21 October 2026.