Table 1

Characteristics of included trials

Trial identifier/nameTrial typeTherapyNo. of patientsTrial periodORRInclusion criterionHPV testMedian follow-up (months)
NCT03082534/not applicable10Non-randomized, multicenter, phase 2 trialCetuximab+pembrolizumab332017–2019Primary endpoint, per RECIST 1.1 by investigators.No previous immunotherapy or EGFR inhibition; platinum-resistant or platinum-ineligible.Oropharyngeal tumors: (methods not specified) by local institution. Non-oropharyngeal tumors: HPV negative.7.3 (IQR: 3.9–10.9)
NCT03370276/not applicable
Cohort A11
Non-randomized, multicenter, phase 1/2 trialCetuximab+nivolumab47*2017–2019Secondary endpoint, per RECIST 1.1 (not specified by investigators or central review).Prior exposure to any systemic therapy including cetuximab or PD-1 inhibitors;
platinum resistant.
p16 immunohistochemistry (no other information).32.1
NCT03370276/not applicable
Cohort B11
Non-randomized, multicenter, phase 2 trialCetuximab+nivolumab48†Not reportSecondary endpoint, per RECIST 1.1 (not specified by investigators or central review).No systemic therapy.p16 immunohistochemistry (no other information).15.9 (95% CI 12.2 to 18.8)‡
NCT02105636/CheckMate 1415 6Randomized, multicenter, phase 3 trialNivolumab versus single-agent systemic therapy240§2014–2015Secondary endpoint, per RECIST 1.1 by investigators.No previous immunotherapy; platinum resistant.Oropharyngeal tumors: p16 immunohistochemistry by local institution.
Non-oropharyngeal tumors: unknown HPV status.
≥ 24.2¶
NCT02252042/KEYNOTE-0401**Randomized, multicenter, phase 3 trialPembrolizumab versus single-agent systemic therapy247††2014–2016Secondary endpoint, per RECIST 1.1 by central review.No previous immunotherapy; platinum resistant.Oropharyngeal tumors: p16 immunohistochemistry by local or central testing.
Non-oropharyngeal tumors: HPV negative.
8.4 (range: 3.3–14.5) in the pembrolizumab group
NCT01848834/KEYNOTE-0122Non-randomized, multicenter, phase 1b trialPembrolizumab60 hours‡‡2013.6–2013.10Primary endpoint, per RECIST 1.1 by central review.No previous immunotherapy.Oropharyngeal tumors: mostly p16 immunohistochemistry by local institution.
Non-oropharyngeal tumors: HPV negative.
13 months (range: 1–26)
NCT01848834/KEYNOTE-012 expansion13Non-randomized, multicenter, phase 1b trialPembrolizumab132§§2014–2015Primary endpoint, per RECIST 1.1 by central review.No previous immunotherapy.Oropharyngeal tumors: mostly p16 immunohistochemistry by local institution.
Non-oropharyngeal tumors: HPV negative.
9 (IQR: 3–11)
NCT02255097/KEYNOTE-0553Non-randomized, multicenter, phase 2 trialPembrolizumab171¶¶2014–2015Primary endpoint, per RECIST 1.1 by central review.No previous immunotherapy; platinum-resistant; cetuximab-resistant.Oropharyngeal tumors: mostly p16 immunohistochemistry by local institution.
Non-oropharyngeal tumors: HPV negative.
7 (range: 0–17)
  • *Forty-three and 45 patients were evaluable for the ORR and the 1-year OS rate analysis, respectively.

  • †Forty-two and 43 patients were evaluable for the ORR and the 1-year OS rate analysis, respectively.

  • ‡For patients including both cohort A and cohort B, and the duration of follow-up was not reported in the cohort B group.

  • §Among the 240 patients assigned to receive nivolumab monotherapy (121 to receive standard therapy), 120 patients were included for the ORR and the 1-year OS rate analysis, respectively.

  • ¶For patients in both nivolumab and single-agent systemic therapy group, and the duration of follow-up was not reported in the nivolumab group.

  • **The relevant data was reported in the documents submitted to the European Medicines Evaluation Agency for approval.24

  • ††The 247 patients were assigned to receive pembrolizumab monotherapy.

  • ‡‡Forty-five and 56 patients were evaluable for the ORR and the 1-year OS rate analysis, respectively.

  • §§104 patients with tumor location in the oral cavity, oropharynx, larynx, and hypopharynx were included for the ORR analysis, and no data were reported for the 1-year OS rate analysis, respectively.

  • ¶¶168 patients were evaluable for the ORR and the 1-year OS rate analysis, respectively.

  • CI, confidence interval; EGFR, epidermal growth factor receptor; HPV, human papillomavirus; IQR, interquartile range; ORR, objective response rate; PD-1, programmed cell death protein 1; RECIST v1.1, Response Evaluation Criteria in Solid Tumors, version 1.1.