# Recurrent or metastatic cervical cancer

Source: https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/  
OnCo record `recurrent-metastatic-cervical-cancer` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

KEYNOTE-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.

After 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Persistent, recurrent or metastatic cervical cancer; Stage IVB cervical cancer; Advanced cervical cancer
- Tags: subtype-page
- 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/recurrent-metastatic-cervical-cancer/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/#what-it-is [7 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/#treating-it [5 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/#evidence [22 trials, 5 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/#science [7 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/#living-with-it [21 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/coming/ [14 medicines, 22 trials, 1 idea, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/data/ [82 connected records]

## Standard of care

- First line: 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. ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [KEYNOTE-826](https://onco.cc/trials/keynote-826/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [BEATcc / ENGOT-Cx10 / GOG-3030](https://onco.cc/trials/beatcc/), [Cadonilimab](https://onco.cc/drugs/cadonilimab/), [COMPASSION-16 / AK104-303](https://onco.cc/trials/compassion-16/), [PD-L1](https://onco.cc/targets/pdl1/))
- Second line after platinum: Tisotumab vedotin (innovaTV 301) with prophylactic eye care; cemiplimab (EMPOWER-Cervical 1) if no prior immunotherapy. ([Tisotumab vedotin](https://onco.cc/drugs/tisotumab-vedotin/), [innovaTV 301 / ENGOT-cx12 / GOG-3057](https://onco.cc/trials/innovatv-301/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [EMPOWER-Cervical 1 / GOG-3016 / ENGOT-cx9](https://onco.cc/trials/empower-cervical-1/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/))
- HER2-expressing disease: Trastuzumab deruxtecan after prior therapy (DESTINY-PanTumor02). ([Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/), [HER2](https://onco.cc/targets/her2/))
- Later lines: Single-agent chemotherapy (topotecan, gemcitabine, pemetrexed, vinorelbine) with modest response; clinical trials of new antibody-drug conjugates and cell therapy preferred. ([Topotecan](https://onco.cc/drugs/topotecan/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Sacituzumab tirumotecan](https://onco.cc/drugs/sacituzumab-tirumotecan/), [Lifileucel](https://onco.cc/drugs/lifileucel/))
- Isolated pelvic recurrence after radiotherapy: Pelvic exenteration in fit patients without sidewall fixation. ([Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cervical_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Cervical_cancer

## Connected records

- cancers: [Adenosquamous carcinoma of the cervix](https://onco.cc/cancers/cervical-adenosquamous-carcinoma/), [Cervical cancer](https://onco.cc/cancers/cervical/), [Early cervical cancer and fertility-sparing surgery](https://onco.cc/cancers/early-cervical-cancer/), [Locally advanced cervical cancer](https://onco.cc/cancers/locally-advanced-cervical-cancer/), [Metastatic and recurrent anal squamous cell carcinoma](https://onco.cc/cancers/metastatic-anal-cancer/), [Small cell neuroendocrine carcinoma of the cervix](https://onco.cc/cancers/cervical-small-cell-neuroendocrine-carcinoma/)
- trials: [A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Canc](https://onco.cc/trials/nct07216703/), [A Phase II Trial of SHR-A1811 in HER2-Expressing Recurrent/Metastatic Cervical Cancer](https://onco.cc/trials/nct07051486/), [A Study of BL-B01D1 + Pembrolizumab ± Bevacizumab in Patients With Recurrent or Metastatic Cervical Cancer and Endometrial Cancer](https://onco.cc/trials/nct07054567/), [A Study of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in Patients With Recurrent or Metastatic Cervical Cancer and Other Gynecological Malignancies](https://onco.cc/trials/nct05990803/), [A Study of GLS-010 Plus Platinum-containing Chemotherapy±Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervic](https://onco.cc/trials/nct05798819/), [A Study of RC48-ADC Combination With Zimberelimab Injection Therapies at Least First-line Platinum-containing Standard Therapy Failed With Recurrent o](https://onco.cc/trials/nct06155396/), [A Study of SHR-A2102 Versus Investigator's Choice of Chemotherapy in Patients With Platinum-based Chemotherapy and PD-(L)1 Inhibitor Treatment Failed Recurrent or Metastatic Cervical Cancer](https://onco.cc/trials/nct07418749/), [A Study to Compare Sacituzumab Tirumotecan (MK-2870) Monotherapy Versus Treatment of Physician's Choice as Second-line Treatment for Participants With](https://onco.cc/trials/nct06459180/), [A Study to Evaluate 9MW2821 Versus Treatment of Physician's Choice for Subjects With Recurrent or Metastatic Cervical Cancer](https://onco.cc/trials/nct06692166/), [Autologous Tumor Infiltrating Lymphocytes (GT101 Injection) in Patients With Recurrent or Metastatic Cervical Cancer](https://onco.cc/trials/nct06241781/), [BAT1308 Combined with Platinum-Based Chemotherapy± Bevacizumab for PDL1-Positive (CPS ≥1) Cervical Cancer](https://onco.cc/trials/nct06123884/), [BEATcc / ENGOT-Cx10 / GOG-3030](https://onco.cc/trials/beatcc/), [Camrelizumab Combined With Famitinib Malate for Treatment of Recurrent/Metastatic Cervical Cancer](https://onco.cc/trials/nct04906993/), [CheckMate 358](https://onco.cc/trials/checkmate-358/), [COMPASSION-16 / AK104-303](https://onco.cc/trials/compassion-16/), [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/), [EMPOWER-Cervical 1 / GOG-3016 / ENGOT-cx9](https://onco.cc/trials/empower-cervical-1/), [innovaTV 301 / ENGOT-cx12 / GOG-3057](https://onco.cc/trials/innovatv-301/), [KEYNOTE-826](https://onco.cc/trials/keynote-826/), [Phase III Study of Socazolimab as First-Line Treatment in Persistent, Recurrent, or Metastatic Cervical Cancer](https://onco.cc/trials/nct06459687/), [PRGN-2009 in Combination With Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer](https://onco.cc/trials/nct06157151/), [SHR-A1811 Combination Regimen for the Treatment of Recurrent or Metastatic Cervical Cancer](https://onco.cc/trials/nct06859775/)
- key papers: [DESTINY-PanTumor02: trastuzumab deruxtecan in HER2-expressing solid tumours](https://onco.cc/key-papers/paper-destiny-pantumor02-jco-2024/), [EMPOWER-Cervical 1: cemiplimab versus chemotherapy in recurrent cervical cancer after platinum](https://onco.cc/key-papers/paper-empower-cervical-1-cemiplimab-nejm-2022/), [GOG 240: bevacizumab added to chemotherapy for advanced cervical cancer](https://onco.cc/key-papers/paper-gog-240-bevacizumab-cervical-nejm-2014/), [innovaTV 301: tisotumab vedotin versus chemotherapy as second- or third-line therapy for recurrent cervical cancer](https://onco.cc/key-papers/paper-innovatv-301-tisotumab-nejm-2024/), [KEYNOTE-826: pembrolizumab plus chemotherapy with or without bevacizumab for persistent, recurrent or metastatic cervical cancer](https://onco.cc/key-papers/paper-keynote-826-nejm-2021/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Cadonilimab](https://onco.cc/drugs/cadonilimab/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Lifileucel](https://onco.cc/drugs/lifileucel/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Sacituzumab tirumotecan](https://onco.cc/drugs/sacituzumab-tirumotecan/), [Tisotumab vedotin](https://onco.cc/drugs/tisotumab-vedotin/), [Topotecan](https://onco.cc/drugs/topotecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- ideas: [HPV circulating tumour DNA to guide cervical cancer therapy](https://onco.cc/ideas/idea-hpv-ctdna-cervical/)
- targets: [HER2](https://onco.cc/targets/her2/), [PD-L1](https://onco.cc/targets/pdl1/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/)
- people: [Krishnansu S. Tewari](https://onco.cc/people/krishnansu-tewari/)
- biomarkers: [Tissue factor expression](https://onco.cc/biomarkers/tissue-factor-expression/)

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JSON: https://onco.cc/api/v1/entities/recurrent-metastatic-cervical-cancer.json