{"entity":{"id":"recurrent-metastatic-nasopharyngeal-carcinoma","kind":"cancer","name":"Recurrent and metastatic nasopharyngeal carcinoma","aka":["R/M NPC","Metastatic nasopharyngeal carcinoma","Locally recurrent nasopharyngeal carcinoma","Stage IVB nasopharyngeal carcinoma"],"tldr":"Recurrent or metastatic nasopharyngeal carcinoma is nasopharyngeal cancer that has come back after radiotherapy or spread to the bones, liver or lungs. Gemcitabine with cisplatin is the chemotherapy backbone, adding a PD-1 antibody such as toripalimab in JUPITER-02 and later trials lengthened survival and became standard, and local recurrence is treated with endoscopic surgery or re-irradiation.","summary":"Nasopharyngeal carcinoma recurs in two ways that are treated differently. Local or regional recurrence after radiotherapy, in the nasopharynx or neck, is potentially curable: endoscopic nasopharyngectomy, shown in a Chinese randomised trial (Lancet Oncology 2021) to give better survival and fewer complications than re-irradiation for resectable recurrence, neck dissection for nodal relapse, and hyperfractionated intensity-modulated re-irradiation, which in a further randomised trial (Lancet 2023) reduced the severe late toxicity of a second course of radiotherapy. Distant metastases, most often to bone, liver and lung, are incurable in most patients, although a minority with oligometastatic disease gain from locoregional radiotherapy of the primary added to chemotherapy, as a Chinese phase 3 (JAMA Oncology 2020) showed.\n\nSystemic therapy for metastatic disease was standardised by the GEM20110714 trial (Lancet 2016), in which gemcitabine and cisplatin beat fluorouracil and cisplatin on progression-free survival (7.0 against 5.6 months) and overall survival. Because EBV-driven tumours are inflamed and PD-L1-rich, PD-1 antibodies were tested next, almost entirely by Chinese companies and investigators: JUPITER-02 (Nature Medicine 2021, JAMA 2023) added toripalimab to gemcitabine-cisplatin in 289 patients and lengthened progression-free survival from 8.0 to 11.7 months with a survival benefit, leading to approval in China in 2021 and in the United States in October 2023, the first approval of a Chinese-developed PD-1 antibody there and the first drug approved for nasopharyngeal carcinoma; CAPTAIN-1st (camrelizumab, Lancet Oncology 2021) and RATIONALE-309 (tislelizumab) showed the same pattern, and penpulimab with gemcitabine-cisplatin was approved in the United States in April 2025. PD-1 antibodies alone are used after platinum failure (nivolumab, pembrolizumab, camrelizumab and toripalimab all have phase 2 data), and later lines include gemcitabine-based or taxane-based chemotherapy, capecitabine and the anti-EGFR antibody nimotuzumab in China. The pipeline is dominated by antibody-drug conjugates, notably the EGFR-directed MRG003 and the EGFR-HER3 bispecific BL-B01D1 and the B7-H3-directed YL201, in phase 3 against chemotherapy, and by EBV-specific T-cell therapies, which have produced durable responses in small trials. Plasma EBV DNA tracks response, and locoregional radiotherapy for de novo metastatic disease with a good chemotherapy response is now guideline-endorsed.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Nasopharyngeal_carcinoma","links":[{"label":"JUPITER-02 (JAMA 2023)","url":"https://doi.org/10.1001/jama.2023.20181"},{"label":"CSCO-ASCO NPC guideline 2021","url":"https://doi.org/10.1200/JCO.20.03237"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Nasopharyngeal_carcinoma"}],"tags":["subtype-page","head-and-neck"],"related":["locoregionally-advanced-nasopharyngeal-carcinoma","nasopharyngeal","recurrent-metastatic-hnscc"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","platinum","imrt-igrt","proton-therapy","tors","tcr-t","liquid-biopsy","sbrt","adc"],"targets":["pd1","pdl1","egfr"],"drugs":["gemcitabine-cisplatin","toripalimab","camrelizumab","tislelizumab","penpulimab","nivolumab","pembrolizumab","capecitabine","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["plasma-ebv-dna","re-irradiation","ebv-term","ctdna"],"trials":["jupiter-02","captain-1st","nct04974398","taishan-301","nct05294172","nct06118333","nct06976190","nct05126719","nct06839066"],"people":[],"bottlenecks":[],"keyPapers":["paper-jupiter-02-toripalimab-chemotherapy-npc-nat-med-2021","paper-zhang-gemcitabine-cisplatin-vs-fluorouracil-cisplatin-rm-npc-lancet-2016","paper-captain-1st-camrelizumab-chemotherapy-npc-lancet-oncol-2021"],"journals":[],"dependsOn":[],"notes":[],"group":"head and neck","burden":"About one in ten patients present with distant metastases and a further fifth relapse after chemoradiotherapy; bone, liver and lung are the usual sites, and survival with modern chemo-immunotherapy now runs to several years.","subtypes":["Locally recurrent nasopharyngeal carcinoma, resectable (endoscopic nasopharyngectomy)","Locally recurrent nasopharyngeal carcinoma, unresectable (hyperfractionated re-irradiation)","Regional nodal recurrence (neck dissection)","De novo metastatic nasopharyngeal carcinoma (chemo-immunotherapy, locoregional radiotherapy in responders)","Oligometastatic nasopharyngeal carcinoma (local therapy to metastases)","Platinum-refractory metastatic nasopharyngeal carcinoma (PD-1 monotherapy, antibody-drug conjugate trials)"],"biomarkers":["Plasma EBV DNA (response and surveillance)","Extent and resectability of local recurrence on MRI and endoscopy","Number and sites of metastases (oligometastatic definition)","PD-L1 (not required; PD-1 benefit regardless)","EGFR, HER3 and B7-H3 expression (antibody-drug conjugate trials)","HLA type and EBV antigen expression (EBV-specific T-cell therapy trials)"],"standardOfCare":[{"setting":"Resectable local recurrence","approach":"Endoscopic nasopharyngectomy (better survival and fewer complications than re-irradiation in a randomised trial); neck dissection for nodal recurrence.","refs":["tors","robotic-surgery","lymphadenectomy"],"guideline":{"version":"CSCO/ASCO guideline on nasopharyngeal carcinoma 2021; NCCN Head and Neck Cancers","url":"https://doi.org/10.1200/JCO.20.03237"}},{"setting":"Unresectable local recurrence","approach":"Hyperfractionated intensity-modulated re-irradiation or proton therapy with careful dose constraints; systemic therapy where re-irradiation is unsafe.","refs":["re-irradiation","imrt-igrt","proton-therapy"],"guideline":{"version":"CSCO/ASCO guideline on nasopharyngeal carcinoma 2021; NCCN Head and Neck Cancers","url":"https://doi.org/10.1200/JCO.20.03237"}},{"setting":"Metastatic disease, first line","approach":"Gemcitabine and cisplatin with a PD-1 antibody (toripalimab, JUPITER-02; camrelizumab, CAPTAIN-1st; tislelizumab; penpulimab), then PD-1 maintenance; locoregional radiotherapy to the primary in patients with a good response.","refs":["gemcitabine-cisplatin","toripalimab","jupiter-02","camrelizumab","captain-1st","tislelizumab","penpulimab","nct04974398","imrt-igrt","checkpoint-inhibitor"],"guideline":{"version":"CSCO/ASCO guideline on nasopharyngeal carcinoma 2021; NCCN Head and Neck Cancers","url":"https://doi.org/10.1200/JCO.20.03237"}},{"setting":"After platinum and PD-1 therapy","approach":"Gemcitabine, taxane or capecitabine-based chemotherapy; nivolumab or pembrolizumab if no prior PD-1 antibody; trials of antibody-drug conjugates (MRG003, BL-B01D1, YL201) and EBV-specific T cells.","refs":["nivolumab","pembrolizumab","capecitabine","taishan-301","nct05294172","nct06118333","nct06976190","nct05126719","nct06839066","tcr-t"],"guideline":{"version":"CSCO/ASCO guideline on nasopharyngeal carcinoma 2021; NCCN Head and Neck Cancers","url":"https://doi.org/10.1200/JCO.20.03237"}},{"setting":"Oligometastatic disease","approach":"Stereotactic radiotherapy or resection of limited metastases with systemic therapy.","refs":["sbrt"],"guideline":{"version":"CSCO/ASCO guideline on nasopharyngeal carcinoma 2021; NCCN Head and Neck Cancers","url":"https://doi.org/10.1200/JCO.20.03237"}}],"stateOfArt":["Chemo-immunotherapy with a PD-1 antibody is standard first line and has produced the first drug approvals for the disease.","Endoscopic surgery and hyperfractionated re-irradiation have made local recurrence curable with less harm.","Antibody-drug conjugates and EBV-specific T cells are the next wave, largely from Chinese trials."],"history":[{"year":2016,"title":"GEM20110714: gemcitabine-cisplatin becomes first-line standard for metastatic disease","refs":["gemcitabine-cisplatin"]},{"year":2020,"title":"Locoregional radiotherapy added to chemotherapy improves survival in de novo metastatic disease","refs":["imrt-igrt"]},{"year":2021,"title":"JUPITER-02 and CAPTAIN-1st: PD-1 antibodies with gemcitabine-cisplatin lengthen progression-free survival; endoscopic nasopharyngectomy beats re-irradiation","refs":["jupiter-02","captain-1st","toripalimab","camrelizumab"]},{"year":2023,"title":"Toripalimab approved in the United States for nasopharyngeal carcinoma; hyperfractionated re-irradiation trial published","refs":["toripalimab","re-irradiation"]},{"year":2025,"title":"Penpulimab with gemcitabine-cisplatin approved in the United States","refs":["penpulimab","nct04974398"]}],"pipeline":["taishan-301","nct05294172","nct06118333","nct06976190","nct05126719","nct06839066","yl201","kl-a167","mrg003","hmbd-001","tcr-t"],"openProblems":["Median survival in metastatic disease is still a few years.","Which patients with local recurrence should have surgery rather than re-irradiation depends on surgical expertise concentrated in a few centres.","Most trials are Chinese and endemic; applicability to non-endemic keratinising disease is uncertain.","EBV-specific cell therapies have not yet reached a positive phase 3."],"parent":"nasopharyngeal"},"route":"/cancers/recurrent-metastatic-nasopharyngeal-carcinoma/","neighbours":{"cancer":[{"id":"locoregionally-advanced-nasopharyngeal-carcinoma","kind":"cancer","name":"Locoregionally advanced nasopharyngeal carcinoma (stage III to IVA)","route":"/cancers/locoregionally-advanced-nasopharyngeal-carcinoma/"},{"id":"nasopharyngeal","kind":"cancer","name":"Nasopharyngeal carcinoma","route":"/cancers/nasopharyngeal/"},{"id":"recurrent-metastatic-hnscc","kind":"cancer","name":"Recurrent or metastatic head and neck squamous cell carcinoma","route":"/cancers/recurrent-metastatic-hnscc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"},{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"},{"id":"tors","kind":"technology","name":"Transoral robotic surgery (TORS)","route":"/technologies/tors/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"camrelizumab","kind":"drug","name":"Camrelizumab","route":"/drugs/camrelizumab/"},{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"gemcitabine-cisplatin","kind":"drug","name":"Gemcitabine + cisplatin","route":"/drugs/gemcitabine-cisplatin/"},{"id":"hmbd-001","kind":"drug","name":"HMBD-001","route":"/drugs/hmbd-001/"},{"id":"kl-a167","kind":"drug","name":"KL-A167","route":"/drugs/kl-a167/"},{"id":"mrg003","kind":"drug","name":"MRG003","route":"/drugs/mrg003/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"penpulimab","kind":"drug","name":"Penpulimab","route":"/drugs/penpulimab/"},{"id":"tislelizumab","kind":"drug","name":"Tislelizumab","route":"/drugs/tislelizumab/"},{"id":"toripalimab","kind":"drug","name":"Toripalimab","route":"/drugs/toripalimab/"},{"id":"yl201","kind":"drug","name":"YL201","route":"/drugs/yl201/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"ebv-term","kind":"term","name":"Epstein-Barr virus (EBV) in cancer","route":"/terms/ebv-term/"},{"id":"lymphadenectomy","kind":"term","name":"Lymphadenectomy (lymph node dissection)","route":"/terms/lymphadenectomy/"},{"id":"plasma-ebv-dna","kind":"term","name":"Plasma EBV DNA","route":"/terms/plasma-ebv-dna/"},{"id":"re-irradiation","kind":"term","name":"Re-irradiation","route":"/terms/re-irradiation/"}],"trial":[{"id":"nct06839066","kind":"trial","name":"A Phase II Study to Evaluate HLX43 in Subjects With Recurrent/Metastatic Nasopharyngeal Carcinoma Failed or Intolerance to Second-line Therapy","route":"/trials/nct06839066/"},{"id":"taishan-301","kind":"trial","name":"A Phase III Study of YL201 in Recurrent or Metastatic Nasopharyngeal Carcinoma(TAISHAN-301)","route":"/trials/taishan-301/"},{"id":"nct06118333","kind":"trial","name":"A Study Comparing BL-B01D1 With Physician's Choice of Chemotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma(PANKU-NPC01)","route":"/trials/nct06118333/"},{"id":"nct06976190","kind":"trial","name":"A Study of MRG003 in Combination With Pucotenlimab Versus Chemotherapy in the Treatment of Patients With Recurrent or Metastatic Nasopharyngeal Carcin","route":"/trials/nct06976190/"},{"id":"nct04974398","kind":"trial","name":"A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma","route":"/trials/nct04974398/"},{"id":"nct05126719","kind":"trial","name":"A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma","route":"/trials/nct05126719/"},{"id":"captain-1st","kind":"trial","name":"CAPTAIN-1st","route":"/trials/captain-1st/"},{"id":"jupiter-02","kind":"trial","name":"JUPITER-02","route":"/trials/jupiter-02/"},{"id":"nct05294172","kind":"trial","name":"KL-A167 Injection Combined With Cisplatin and Gemcitabine vs Placebo Combined With Cisplatin and Gemcitabine in the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma","route":"/trials/nct05294172/"}],"paper":[{"id":"paper-captain-1st-camrelizumab-chemotherapy-npc-lancet-oncol-2021","kind":"paper","name":"CAPTAIN-1st: camrelizumab versus placebo with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma","route":"/key-papers/paper-captain-1st-camrelizumab-chemotherapy-npc-lancet-oncol-2021/"},{"id":"paper-zhang-gemcitabine-cisplatin-vs-fluorouracil-cisplatin-rm-npc-lancet-2016","kind":"paper","name":"Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma","route":"/key-papers/paper-zhang-gemcitabine-cisplatin-vs-fluorouracil-cisplatin-rm-npc-lancet-2016/"},{"id":"paper-jupiter-02-toripalimab-chemotherapy-npc-nat-med-2021","kind":"paper","name":"JUPITER-02: toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma","route":"/key-papers/paper-jupiter-02-toripalimab-chemotherapy-npc-nat-med-2021/"}]}}