# Recurrent and metastatic nasopharyngeal carcinoma

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

## TL;DR

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.

Systemic 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: R/M NPC; Metastatic nasopharyngeal carcinoma; Locally recurrent nasopharyngeal carcinoma; Stage IVB nasopharyngeal carcinoma
- Tags: subtype-page; head-and-neck
- 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)

## Standard of care

- Resectable local recurrence: Endoscopic nasopharyngectomy (better survival and fewer complications than re-irradiation in a randomised trial); neck dissection for nodal recurrence. ([Transoral robotic surgery (TORS)](https://onco.cc/technologies/tors/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/))
- Unresectable local recurrence: Hyperfractionated intensity-modulated re-irradiation or proton therapy with careful dose constraints; systemic therapy where re-irradiation is unsafe. ([Re-irradiation](https://onco.cc/terms/re-irradiation/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/))
- Metastatic disease, first line: 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. ([Gemcitabine + cisplatin](https://onco.cc/drugs/gemcitabine-cisplatin/), [Toripalimab](https://onco.cc/drugs/toripalimab/), [JUPITER-02](https://onco.cc/trials/jupiter-02/), [Camrelizumab](https://onco.cc/drugs/camrelizumab/), [CAPTAIN-1st](https://onco.cc/trials/captain-1st/), [Tislelizumab](https://onco.cc/drugs/tislelizumab/), [Penpulimab](https://onco.cc/drugs/penpulimab/), [A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma](https://onco.cc/trials/nct04974398/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/))
- After platinum and PD-1 therapy: 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. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Capecitabine](https://onco.cc/drugs/capecitabine/), [A Phase III Study of YL201 in Recurrent or Metastatic Nasopharyngeal Carcinoma(TAISHAN-301)](https://onco.cc/trials/taishan-301/), [KL-A167 Injection Combined With Cisplatin and Gemcitabine vs Placebo Combined With Cisplatin and Gemcitabine in the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma](https://onco.cc/trials/nct05294172/), [A Study Comparing BL-B01D1 With Physician's Choice of Chemotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma(PANKU-NPC01)](https://onco.cc/trials/nct06118333/), [A Study of MRG003 in Combination With Pucotenlimab Versus Chemotherapy in the Treatment of Patients With Recurrent or Metastatic Nasopharyngeal Carcin](https://onco.cc/trials/nct06976190/), [A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma](https://onco.cc/trials/nct05126719/), [A Phase II Study to Evaluate HLX43 in Subjects With Recurrent/Metastatic Nasopharyngeal Carcinoma Failed or Intolerance to Second-line Therapy](https://onco.cc/trials/nct06839066/), [TCR-T cell therapy](https://onco.cc/technologies/tcr-t/))
- Oligometastatic disease: Stereotactic radiotherapy or resection of limited metastases with systemic therapy. ([SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Nasopharyngeal_carcinoma
- JUPITER-02 (JAMA 2023): https://doi.org/10.1001/jama.2023.20181
- CSCO-ASCO NPC guideline 2021: https://doi.org/10.1200/JCO.20.03237
- Wikipedia: https://en.wikipedia.org/wiki/Nasopharyngeal_carcinoma

## Connected records

- cancers: [Locoregionally advanced nasopharyngeal carcinoma (stage III to IVA)](https://onco.cc/cancers/locoregionally-advanced-nasopharyngeal-carcinoma/), [Nasopharyngeal carcinoma](https://onco.cc/cancers/nasopharyngeal/), [Recurrent or metastatic head and neck squamous cell carcinoma](https://onco.cc/cancers/recurrent-metastatic-hnscc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Platinum agents](https://onco.cc/technologies/platinum/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [TCR-T cell therapy](https://onco.cc/technologies/tcr-t/), [Transoral robotic surgery (TORS)](https://onco.cc/technologies/tors/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Camrelizumab](https://onco.cc/drugs/camrelizumab/), [Capecitabine](https://onco.cc/drugs/capecitabine/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Gemcitabine + cisplatin](https://onco.cc/drugs/gemcitabine-cisplatin/), [HMBD-001](https://onco.cc/drugs/hmbd-001/), [KL-A167](https://onco.cc/drugs/kl-a167/), [MRG003](https://onco.cc/drugs/mrg003/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Penpulimab](https://onco.cc/drugs/penpulimab/), [Tislelizumab](https://onco.cc/drugs/tislelizumab/), [Toripalimab](https://onco.cc/drugs/toripalimab/), [YL201](https://onco.cc/drugs/yl201/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Epstein-Barr virus (EBV) in cancer](https://onco.cc/terms/ebv-term/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/), [Plasma EBV DNA](https://onco.cc/terms/plasma-ebv-dna/), [Re-irradiation](https://onco.cc/terms/re-irradiation/)
- trials: [A Phase II Study to Evaluate HLX43 in Subjects With Recurrent/Metastatic Nasopharyngeal Carcinoma Failed or Intolerance to Second-line Therapy](https://onco.cc/trials/nct06839066/), [A Phase III Study of YL201 in Recurrent or Metastatic Nasopharyngeal Carcinoma(TAISHAN-301)](https://onco.cc/trials/taishan-301/), [A Study Comparing BL-B01D1 With Physician's Choice of Chemotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma(PANKU-NPC01)](https://onco.cc/trials/nct06118333/), [A Study of MRG003 in Combination With Pucotenlimab Versus Chemotherapy in the Treatment of Patients With Recurrent or Metastatic Nasopharyngeal Carcin](https://onco.cc/trials/nct06976190/), [A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma](https://onco.cc/trials/nct04974398/), [A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma](https://onco.cc/trials/nct05126719/), [CAPTAIN-1st](https://onco.cc/trials/captain-1st/), [JUPITER-02](https://onco.cc/trials/jupiter-02/), [KL-A167 Injection Combined With Cisplatin and Gemcitabine vs Placebo Combined With Cisplatin and Gemcitabine in the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma](https://onco.cc/trials/nct05294172/)
- key papers: [CAPTAIN-1st: camrelizumab versus placebo with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma](https://onco.cc/key-papers/paper-captain-1st-camrelizumab-chemotherapy-npc-lancet-oncol-2021/), [Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma](https://onco.cc/key-papers/paper-zhang-gemcitabine-cisplatin-vs-fluorouracil-cisplatin-rm-npc-lancet-2016/), [JUPITER-02: toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma](https://onco.cc/key-papers/paper-jupiter-02-toripalimab-chemotherapy-npc-nat-med-2021/)

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