Exploration of Medicine

Table 4. Summary of key clinical trials of systemic therapies in recurrent/metastatic NPC.

Trial	Regimen	Setting/Line	n	Key efficacy results	EBV status
GEM20110714	Gem + Cis vs. 5-FU + Cis	R/M NPC, 1st-line	362	mOS 22.1 vs. 18.6 mo (HR 0.72); mPFS 7.0 vs. 5.6 mo	Not stratified
JUPITER-02	Toripalimab + Gem/Cis vs. Gem/Cis	R/M NPC, 1st-line	289	mPFS 21.4 vs. 8.2 mo (HR 0.52); OS benefit (HR 0.63). FDA-approved Oct 2023	EBV+ majority
CAPTAIN-1st	Camrelizumab + Gem/Cis vs. Gem/Cis	R/M NPC, 1st-line	263	mPFS 9.7 vs. 6.9 mo (HR 0.54); OS immature at primary analysis	Not stratified
RATIONALE-309	Tislelizumab + Gem/Cis vs. Gem/Cis	R/M NPC, 1st-line	263	mPFS 9.6 vs. 7.4 mo (HR 0.52); 3-yr follow-up confirms PFS2 and OS benefit	Not stratified
AK105-304 (penpulimab)	Penpulimab + Gem/Cis vs. Gem/Cis	R/M NPC, 1st-line	291	mPFS 9.6 vs. 7.0 mo (HR 0.49); OS data immature	EBV+ enriched
KEYNOTE-122	Pembrolizumab vs. chemotherapy	R/M NPC, ≥ 2nd-line	233	No OS improvement (HR 0.90); numerically higher ORR in PD-L1-high subgroup	EBV+ majority
ABILITY-1 (Phase I/II)	MDNA11 ± pembrolizumab	Advanced solid tumors, ICI-pretreated	Ongoing	7.7% ORR (monotherapy); responses in anal SCC and MSS-CRC with combo; no DLTs to 120 µg/kg	Mixed histologies
BL-B01D1-303	Izalontamab brengitecan (EGFR/HER3 bisp. ADC) vs. chemo	R/M NPC, pretreated	~400	Superior PFS vs. chemotherapy (phase III, Nov 2025)	Not stratified

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5-FU: 5-fluorouracil; ADC: antibody-drug conjugate; EBV: Epstein–Barr virus; Gem/Cis: gemcitabine plus cisplatin; DLT: dose-limiting toxicity; EGFR: epidermal growth factor receptor; HER3: human epidermal growth factor receptor 3; HR: hazard ratio; ICI: immune checkpoint inhibitor; mOS: median overall survival; mPFS: median progression-free survival; MSS-CRC: microsatellite stable colorectal carcinoma; ORR: objective response rate; PD-L1: programmed death-ligand 1; R/M: recurrent/metastatic; SCC: squamous cell carcinoma.

Declarations

Acknowledgments

We sincerely acknowledge all the patients and their families, whose trust and participation have been the driving force behind this research.

Author contributions

CGR: Conceptualization, Data curation, Methodology, Investigation, Writing—original draft, Writing—review & editing. SCC: Data curation, Validation, Methodology, Investigation, Writing—review & editing. MPK: Data curation, Validation, Methodology, Software. ARR: Methodology, Validation, Writing—review & editing. OJGCM: Validation, Writing—review & editing. SJCS: Validation, Writing—review & editing. BCO: Data curation, Visualization, Investigation, Methodology, Supervision, Writing—original draft, Writing—review & editing. LCG: Conceptualization, Data curation, Validation, Methodology, Investigation, Supervision, Writing—original draft, Writing—review & editing. All authors read and approved the final version of the manuscript.

Conflicts of interest

Luis Cabezón-Gutiérrez declares the following conflicts of interest: Advisory roles: AstraZeneca, Roche, Eisai, and Bristol-Myers Squibb. Speaker’s bureau/honoraria: Roche, AstraZeneca, Bristol-Myers Squibb, Merck Serono, Grünenthal, Pfizer and Eisai. Travel, accommodation, and expenses (Conferences): Merck, Servier. Magda Palka-Kotlowska declares: Advisory roles: GlaxoSmithKline and Esteve. Speaker’s bureau/honoraria: Pfizer, Gilead, Daiichi Sankyo, GlaxoSmithKline, AstraZeneca, and Novartis. Sara Custodio-Cabello declares: Speaker’s bureau / Honoraria: Fresenius, Abbott, Astellas. Claudia García-Ruíz, Otto José Guillermo Chacón-Medina, Samuel Jesús Castañeda-Sánchez, Beatriz Chacón-Ovejero and Adriana Rosero-Rodriguez declare no conflicts of interest.

Ethical approval

Ethical approval for this case report was not required, as it has been exempted in accordance with institutional regulations governing retrospective single-patient reports. This study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Consent to participate

Written informed consent for participation in this case report was obtained from the patient’s next of kin (family members), given that the patient is deceased.

Consent to publication

Written informed consent for publication of this case report, including accompanying clinical images, was obtained from the patient’s next of kin (family members), given that the patient is deceased.

Availability of data and materials

The data that support the findings of this case report are not publicly available due to patient privacy and confidentiality restrictions, but are available from the corresponding author upon reasonable request and subject to institutional approval.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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