{"entity":{"id":"low-grade-serous-ovarian-cancer","kind":"cancer","name":"Low-grade serous ovarian cancer","aka":["LGSOC","Low-grade serous carcinoma"],"tldr":"Low-grade serous cancer is the slow-growing, chemotherapy-resistant cousin of the common ovarian cancer. Surgery and hormone therapy are its mainstays, and MEK inhibitors, alone or combined with a FAK inhibitor, are the first drugs shown to shrink it reliably.","summary":"Low-grade serous carcinoma is a distinct disease with wild-type TP53 and mutations in the MAPK pathway (KRAS, BRAF, NRAS) in about half of cases; it often arises from a serous borderline tumour and expresses oestrogen receptors. Complete surgical removal matters more than in high-grade disease because chemotherapy response rates are low; letrozole or other aromatase inhibitors are used as maintenance and for recurrence. The GOG 281 trial showed that the MEK inhibitor trametinib nearly doubled progression-free survival compared with standard chemotherapy or hormone therapy in recurrent disease, and the combination of avutometinib and defactinib was approved in the United States in 2025 for KRAS-mutant recurrent disease after the RAMP 201 trial.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Ovarian_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ovarian_cancer"}],"tags":["subtype-page"],"related":["high-grade-serous-ovarian-cancer","clear-cell-ovarian-cancer","mucinous-ovarian-cancer","granulosa-cell-tumour"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-gog-281-trametinib-lgsoc-gershenson-lancet-2022","paper-gershenson-hormonal-maintenance-lgsoc-jco-2017","paper-ramp-201-avutometinib-defactinib-lgsoc-jco-2025"],"journals":[],"dependsOn":[],"notes":[],"group":"gynaecologic","burden":"About one in twenty ovarian cancers, affecting younger women, with a median age in the forties; it grows slowly but resists chemotherapy, so patients live for years with disease that is hard to eradicate.","subtypes":["KRAS-mutant (most responsive to MEK and RAF/MEK inhibition)","BRAF or NRAS-mutant","MAPK wild-type","Arising from serous borderline tumour"],"biomarkers":["KRAS, BRAF and NRAS mutations","Oestrogen and progesterone receptor expression","Wild-type TP53 (distinguishes it from high-grade)","CA-125 (less reliable than in high-grade disease)"],"standardOfCare":[{"setting":"First line","approach":"Complete cytoreductive surgery; carboplatin-paclitaxel followed by letrozole maintenance, or letrozole alone in selected patients.","refs":["carboplatin","paclitaxel","letrozole"]},{"setting":"Recurrent disease","approach":"Trametinib (GOG 281) or avutometinib plus defactinib for KRAS-mutant tumours; aromatase inhibitors; secondary surgery where complete resection is possible.","refs":["trametinib","avutometinib-defactinib","letrozole"]},{"setting":"Maintenance","approach":"Letrozole after first-line treatment, continued for years while tolerated.","refs":["letrozole"]}],"stateOfArt":["GOG 281 was the first randomised trial in this rare disease and made trametinib a standard option.","Avutometinib-defactinib is the first approval specific to low-grade serous cancer.","Hormone maintenance is replacing chemotherapy in first-line care."],"history":[{"year":2004,"title":"Two-tier grading separates low-grade from high-grade serous cancer (MD Anderson)","refs":[]},{"year":2022,"title":"GOG 281: trametinib doubles progression-free survival","refs":["trametinib"]},{"year":2025,"title":"Avutometinib plus defactinib approved for KRAS-mutant disease","refs":["avutometinib-defactinib"]}],"pipeline":["avutometinib-defactinib","trametinib"],"openProblems":["Whether first-line chemotherapy adds anything to surgery and hormone therapy.","Options for MAPK wild-type tumours.","Living for decades with a slow but incurable disease."],"parent":"ovarian"},"route":"/cancers/low-grade-serous-ovarian-cancer/","neighbours":{"cancer":[{"id":"granulosa-cell-tumour","kind":"cancer","name":"Adult granulosa cell tumour of the ovary","route":"/cancers/granulosa-cell-tumour/"},{"id":"clear-cell-ovarian-cancer","kind":"cancer","name":"Clear cell ovarian cancer","route":"/cancers/clear-cell-ovarian-cancer/"},{"id":"high-grade-serous-ovarian-cancer","kind":"cancer","name":"High-grade serous ovarian cancer","route":"/cancers/high-grade-serous-ovarian-cancer/"},{"id":"mucinous-ovarian-cancer","kind":"cancer","name":"Mucinous ovarian cancer","route":"/cancers/mucinous-ovarian-cancer/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"platinum-sensitive-ovarian-cancer","kind":"cancer","name":"Platinum-sensitive ovarian cancer","route":"/cancers/platinum-sensitive-ovarian-cancer/"}],"paper":[{"id":"paper-gog-281-trametinib-lgsoc-gershenson-lancet-2022","kind":"paper","name":"GOG 281/LOGS: trametinib versus standard of care in recurrent low-grade serous ovarian cancer","route":"/key-papers/paper-gog-281-trametinib-lgsoc-gershenson-lancet-2022/"},{"id":"paper-gershenson-hormonal-maintenance-lgsoc-jco-2017","kind":"paper","name":"Hormonal maintenance therapy for women with low-grade serous cancer of the ovary or peritoneum","route":"/key-papers/paper-gershenson-hormonal-maintenance-lgsoc-jco-2017/"},{"id":"paper-ramp-201-avutometinib-defactinib-lgsoc-jco-2025","kind":"paper","name":"RAMP 201: avutometinib with or without defactinib in recurrent low-grade serous ovarian cancer","route":"/key-papers/paper-ramp-201-avutometinib-defactinib-lgsoc-jco-2025/"}],"drug":[{"id":"avutometinib-defactinib","kind":"drug","name":"Avutometinib + defactinib","route":"/drugs/avutometinib-defactinib/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","route":"/drugs/letrozole/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"trametinib","kind":"drug","name":"Trametinib","route":"/drugs/trametinib/"}],"person":[{"id":"david-gershenson","kind":"person","name":"David M. Gershenson","route":"/people/david-gershenson/"},{"id":"susana-banerjee","kind":"person","name":"Susana Banerjee","route":"/people/susana-banerjee/"}],"target":[{"id":"fak","kind":"target","name":"FAK (PTK2)","route":"/targets/fak/"}],"trial":[{"id":"nct06072781","kind":"trial","name":"A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer","route":"/trials/nct06072781/"},{"id":"nct06682572","kind":"trial","name":"A Study of Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer in Japanese Patients","route":"/trials/nct06682572/"}]}}