Summary of trial- and patient-level characteristics and clinical endpoints of included trials

ItemsKEYNOTE-028NCI-9742CheckMate-358JS001SHR-1210 (monotherapy)GEM20110714aSHR-1210 (combination)
Trial-level characteristics
 RegionTaiwanInternational-collaboratedInternational-collaboratedMainland ChinaMainland ChinaMainland ChinaMainland China
 Inclusion period2014–20162015–20162015–20172016–20182016–20172012–20152017–2017
 Phase121/22131
 Key eligibility criteriaRecurrent/metastatic NPC; Failure on prior standard therapy; PD-L1 expression ≥1%Recurrent/metastatic NPC; Failure on at least one prior line of platinum-based chemotherapyRecurrent/metastatic NPC; ≤ 2 prior systemic therapiesRecurrent/metastatic NPC; Failure on at least one prior line of platinum-based chemotherapyRecurrent/metastatic NPC; Failure on at least one prior line of platinum-based chemotherapyTreatment-naive recurrent/metastatic NPCTreatment-naive recurrent/metastatic NPC
 Experimental regimenAnti-PD-1: Pembrolizumab 10 mg/kg q2wks up to 2 years or until disease progression or unacceptable toxicityAnti-PD-1: Nivolumab 3 mg/kg q2wks on a 4-week cycle until disease progressionAnti-PD-1: Nivolumab 240 mg/kg q2wks until disease progressionAnti-PD-1: JS001 3 mg/kg q2wks until disease progression or unacceptable toxicityAnti-PD-1: Camrelizumab at escalating doses of 1, 3 and 10 mg/kg, and a bridging dose of 200 mg per dose q2wks until unacceptable toxicityChemotherapy: Gemcitabine 1 g/m2 (days 1 and 8), and cisplatin 80 mg/m2 (day 1) q3wks for six cyclesAnti-PD-1 + chemotherapy: Camrelizumab 200 mg (day 1), gemcitabine 1 g/m2 (days 1 and 8), cisplatin 80 mg/m2 (day 1) q3wks for six cycles followed by camrelizumab 200 mg maintenance q3wks
 Sample size2745241439318123
Patient-level characteristics
 Age, median (range), years52 (18–68)57 (37–76)51 (NR)46 (24–71)45 (38–52)47 (39–55)44 (34–51)
 Sex, male, n (%)21/27 (77.8)35/45 (77.8)21/24 (88%)121/143 (84.6)75/93 (81)148/181 (83.1)17/23 (74)
PD-L1 expressionb
  < 1%, n (%)024/42 (57.1)76/136 (55.9)
  ≥ 1%, n (%)27/27 (100)18/42 (42.9)60/136 (44.1)
Clinical endpoints
 Median follow-up, months20.012.526.0NR9.922.010.2
 ORR (%)26.320.520.823.234.164.190.9
OS
 Median (months)16.517.1NRNRNR29.1NR
 1-year rate (%)63.059.0NRNRNR83.2NR
PFS
 Median (months)6.52.82.4NR9.97.010.2
 1-year rate (%)33.419.3NRNR27.119.661.4
 All grade AEs (%)74.1NR54.292.396.891.7100
 Grade 3–5 AEs (%)29.622.28.324.516.142.887.0

Abbreviations: AEs adverse events, EBV Epstein-Barr virus, GP Gemcitabine and Cisplatin, NPC nasopharyngeal carcinoma, NR not reported, ORR objective response rate, OS overall survival, q2/3wks every 2/3 weeks, PFS progression-free survival, PD-1 programmed death-1, PD-L1 programmed death-ligand 1

a Only paients from the GP arm was included, as it proved that GP regimen significantly prolonged PFS in patients with recurrent or metastatic NPC compared to standard fluorouracil plus cisplatin regimen, and currently GP is used as the first-line therapy for recurrent/metastatic diseases

b Methods of PD-L1 expression evaluation, KEYNOTE-407 trial: The PD-L1 expression was assessed baseline on an archived formalin-fixed, paraffin-embedded tumor sample or a newly obtained biopsy sample using a laboratory-developed prototype immunohistochemical assay (QualTek Molecular Laboratories, Goleta, CA). PD-L1 positivity was defined as membranous staining on 1% or more of a modified proportion score or interface pattern. NCI-9742 trial: The PD-L1 expression was assessed based on paraffin-embedded NPC tumors using the immunohistochemical analysis of PD-L1 (anti-human PD-L1 antibody, clone 22C3, PD-L1 IHC 22C3; pharmDx assay; Agilent Technologies, Santa Clara, CA). PD-L1 expression in tumor cells and immune cells was scored as the percentage of tumor cells and immune cells with membranous straining, respectively. JS001 trial: The PD-L1 expression was assessed based on paraffin-embedded NPC tumors using the immunohistochemical analysis of PD-L1 (anti-human PD-L1 antibody, clone SP142; Spring BioScience, Pleasanton, CA)