Materials and methods
Search strategy
Two authors conducted the search and study review independently. We
searched PubMed, Embase, Cochrane Library, CVID, CBM, CNKI and Web of
Science up to 1 November 2019. The search terms used were: PD-1/PD-L1
inhibitors or Pembrolizumab or Keytruda or Nivolumab or Opdivo or
Durvalumab or MEDI4736 or Atezolizumab or checkpoint inhibitors and head
and neck cancer or HNC or head and neck squamous cell carcinoma or head
and neck neoplasms or HNSCC. We also searched ‘clinicaltrials.gov’ with
the search term Head and Neck Squamous Cell Carcinoma, and we also
searched for Squamous cell carcinoma of head and neck, Squamous cell
carcinoma of the head and neck, head and neck cancer, head and neck
neoplasms or HNSCC and PD-1/PD-L1 inhibitors or Pembrolizumab or
Keytruda or Nivolumab or Opdivo or Durvalumab or MEDI4736 or
Atezolizumab or checkpoint inhibitors.
Study selection
Randomized controlled trials (RCT) were used, and the inclusion criteria
for our meta-analysis were as follows: 1) single drug treatment with
PD-1/PD-L1 inhibitors; 2) the papers should have exact data whether in
the time domain or frequency domain; 3) the groups being compared were
treated with chemotherapy, targeted therapy, a combination of two
immunosuppressive inhibitors or other drug combinations. Exclusion
criteria for the meta-analysis were as follows: 1) non-randomized
trials; 2) studies that were not published in English or Chinese; 3)
studies that did not report the end points of overall response rate
(ORR), overall survival (OS), and progression-free survival (PFS).
Data extraction and quality assessment
Two authors independently examined all potentially relevant studies
identified through the search. We read all of the papers to determine
whether they met our inclusion criteria and decided whether they should
be included. Any disagreements were resolved by consensus. Data were
extracted by one researcher and supervised by another researcher and
included: 1) author information; 2) publication year; 3) number of
patients in the study; 4) treatment plan; 5) study design; 6) the main
results.
Data synthesis and statistical analysis
We used Review Manager software (version 5.0; Cochrane Collaboration,
London, UK) as the tool for calculating the outcomes. The relative risk
(RR) and 95% confidence interval (CI) were used to compare the outcomes
between the different groups. The chi-squared test was used to test
heterogeneity. Cochran’s Q test was applied to assess the heterogeneity
of the different studies. The inconsistency of each study was measured
with the I2 statistic. When I2 ≥ 50%, a random effects model was used
to take account of clinical heterogeneity in the data, otherwise a fixed
effects model was used. Sensitivity analysis was used to analyze the
effect of poor quality studies, and publication bias was analysed using
an inverted funnel chart test.