{"entity":{"id":"recurrent-metastatic-cervical-cancer","kind":"cancer","name":"Recurrent or metastatic cervical cancer","aka":["Persistent, recurrent or metastatic cervical cancer","Stage IVB cervical cancer","Advanced cervical cancer"],"tldr":"Recurrent or metastatic cervical cancer has spread beyond the pelvis or come back where it cannot be cured by surgery or radiotherapy. Pembrolizumab added to chemotherapy and bevacizumab is the first treatment, and the antibody-drug conjugate tisotumab vedotin or the PD-1 antibody cemiplimab extend life when it progresses.","summary":"Persistent disease after chemoradiation, recurrence outside a previously irradiated field and stage IVB disease at presentation are managed together. Isolated central pelvic recurrence after radiotherapy can still be cured by exenteration, and an isolated para-aortic or lung metastasis is sometimes treated with radiotherapy or resection, but most patients need systemic therapy. Cisplatin-paclitaxel was the reference doublet, with carboplatin an equivalent substitute after JCOG0505. GOG-240 added bevacizumab to chemotherapy in 2014 and extended median survival to about seventeen months, the first targeted therapy in the disease. Squamous, adenocarcinoma and adenosquamous histologies are treated alike, and PD-L1 combined positive score is measured because most trials selected or stratified by it.\n\nKEYNOTE-826 added pembrolizumab to platinum-paclitaxel with or without bevacizumab and extended median overall survival in all comers from 16.8 to 26.4 months, with a hazard ratio of 0.63, and to 28.6 months in tumours with a combined positive score of one or more; it was approved in 2021 and is the first-line standard. BEATcc added atezolizumab to chemotherapy plus bevacizumab and reached a median survival of 32.1 months against 22.8, and COMPASSION-16 in China added the PD-1 and CTLA-4 bispecific cadonilimab with a survival hazard ratio of 0.64, confirming the class effect. Fitness for bevacizumab, prior pelvic radiotherapy and the risk of fistula shape the choice of partner drugs.\n\nAfter platinum and immunotherapy, tisotumab vedotin, an antibody-drug conjugate against tissue factor, improved median survival from 9.5 to 11.5 months against chemotherapy in innovaTV 301 and gained full approval in 2024; ocular toxicity requires eye care and steroid drops. Cemiplimab improved survival from 8.5 to 12.0 months against chemotherapy in EMPOWER-Cervical 1 in immunotherapy-naive patients and remains relevant where first-line immunotherapy was not given. Trastuzumab deruxtecan produced responses in half of HER2-expressing cervical cancers in DESTINY-PanTumor02, sacituzumab tirumotecan is in phase 3, and tumour-infiltrating lymphocyte therapy has shown durable responses in small studies. How to sequence antibody-drug conjugates after first-line immunotherapy, and how to bring any of this to the low-income countries where most deaths occur, are the pressing questions.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cervical_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cervical_cancer"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gynaecologic","burden":"Around one in ten cervical cancers present with distant spread and a third of locally advanced cases relapse; median survival was about a year before 2014, and first-line chemo-immunotherapy has now more than doubled it for many women.","subtypes":["Stage IVB at presentation (distant metastasis)","Persistent or recurrent disease after chemoradiation","PD-L1 combined positive score 1 or more (largest pembrolizumab benefit)","Squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma (treated alike)","HER2-expressing cervical cancer (trastuzumab deruxtecan)","Isolated central pelvic recurrence (exenteration with curative intent)","Small cell neuroendocrine carcinoma of the cervix (platinum-etoposide, separate pathway)"],"biomarkers":["PD-L1 combined positive score","Tissue factor expression (not required for tisotumab vedotin)","HER2 immunohistochemistry (trastuzumab deruxtecan)","HPV type and circulating HPV DNA","Prior pelvic radiotherapy and fistula risk (bevacizumab)","MSI and tumour mutational burden (rare)"],"standardOfCare":[{"setting":"First line","approach":"Pembrolizumab with cisplatin or carboplatin, paclitaxel and, when safe, bevacizumab (KEYNOTE-826); atezolizumab with chemotherapy and bevacizumab (BEATcc) or cadonilimab with chemotherapy (COMPASSION-16, China) as alternatives.","refs":["pembrolizumab","keynote-826","cisplatin","carboplatin","paclitaxel","bevacizumab","atezolizumab","beatcc","cadonilimab","compassion-16","pdl1"]},{"setting":"Second line after platinum","approach":"Tisotumab vedotin (innovaTV 301) with prophylactic eye care; cemiplimab (EMPOWER-Cervical 1) if no prior immunotherapy.","refs":["tisotumab-vedotin","innovatv-301","cemiplimab","empower-cervical-1","adc"]},{"setting":"HER2-expressing disease","approach":"Trastuzumab deruxtecan after prior therapy (DESTINY-PanTumor02).","refs":["trastuzumab-deruxtecan","destiny-pantumor02","her2"]},{"setting":"Later lines","approach":"Single-agent chemotherapy (topotecan, gemcitabine, pemetrexed, vinorelbine) with modest response; clinical trials of new antibody-drug conjugates and cell therapy preferred.","refs":["topotecan","gemcitabine","sacituzumab-tirumotecan","lifileucel"]},{"setting":"Isolated pelvic recurrence after radiotherapy","approach":"Pelvic exenteration in fit patients without sidewall fixation.","refs":["robotic-surgery","imrt-igrt"]}],"stateOfArt":["KEYNOTE-826 made chemo-immunotherapy first-line standard and lifted median survival past two years.","Tisotumab vedotin was the first antibody-drug conjugate approved in a gynaecological cancer.","Three different checkpoint agents have now shown survival gains in the first line."],"history":[{"year":2009,"title":"GOG-0204: cisplatin-paclitaxel confirmed as the reference doublet","refs":["cisplatin","paclitaxel"]},{"year":2014,"title":"GOG-0240: bevacizumab extends survival in advanced cervical cancer","refs":["bevacizumab"]},{"year":2021,"title":"KEYNOTE-826: pembrolizumab with chemotherapy extends median survival to 26.4 months","refs":["keynote-826"]},{"year":2021,"title":"Tisotumab vedotin accelerated approval; EMPOWER-Cervical 1 positive for cemiplimab","refs":["tisotumab-vedotin","empower-cervical-1"]},{"year":2023,"title":"innovaTV 301 and BEATcc positive","refs":["innovatv-301","beatcc"]},{"year":2024,"title":"Tisotumab vedotin full approval; COMPASSION-16 positive for cadonilimab in China","refs":["tisotumab-vedotin","compassion-16"]}],"pipeline":["sacituzumab-tirumotecan","trastuzumab-deruxtecan","lifileucel","cadonilimab","idea-hpv-ctdna-cervical"],"openProblems":["Sequencing antibody-drug conjugates and immunotherapy after first-line chemo-immunotherapy.","Fistula and bleeding risk with bevacizumab after pelvic radiotherapy.","Access to any of these drugs in the countries with most deaths."],"parent":"cervical"},"route":"/cancers/recurrent-metastatic-cervical-cancer/","neighbours":{"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"cadonilimab","kind":"drug","name":"Cadonilimab","route":"/drugs/cadonilimab/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"lifileucel","kind":"drug","name":"Lifileucel","route":"/drugs/lifileucel/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"sacituzumab-tirumotecan","kind":"drug","name":"Sacituzumab tirumotecan","route":"/drugs/sacituzumab-tirumotecan/"},{"id":"tisotumab-vedotin","kind":"drug","name":"Tisotumab vedotin","route":"/drugs/tisotumab-vedotin/"},{"id":"topotecan","kind":"drug","name":"Topotecan","route":"/drugs/topotecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"trial":[{"id":"beatcc","kind":"trial","name":"BEATcc / ENGOT-Cx10 / GOG-3030","route":"/trials/beatcc/"},{"id":"compassion-16","kind":"trial","name":"COMPASSION-16 / AK104-303","route":"/trials/compassion-16/"},{"id":"destiny-pantumor02","kind":"trial","name":"DESTINY-PanTumor02","route":"/trials/destiny-pantumor02/"},{"id":"empower-cervical-1","kind":"trial","name":"EMPOWER-Cervical 1 / GOG-3016 / ENGOT-cx9","route":"/trials/empower-cervical-1/"},{"id":"innovatv-301","kind":"trial","name":"innovaTV 301 / ENGOT-cx12 / GOG-3057","route":"/trials/innovatv-301/"},{"id":"keynote-826","kind":"trial","name":"KEYNOTE-826","route":"/trials/keynote-826/"}],"idea":[{"id":"idea-hpv-ctdna-cervical","kind":"idea","name":"HPV circulating tumour DNA to guide cervical cancer therapy","route":"/ideas/idea-hpv-ctdna-cervical/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"}],"cancer":[{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"}]}}