Research Trends and Most Influential Clinical Studies on Anti-PD1/PDL1 Immunotherapy for Cancers: A Bibliometric Analysis

Abstract

In this study, a bibliometric analysis was carried out to identify the most influential clinical studies and research trends on anti-programmed cell death 1/programmed cell death 1 ligand 1 (anti-PD1/PDL1) immunotherapy. On January 1, 2022, we used Web of Science to identify the 100 most frequently cited papers on clinical studies investigating anti-PD1/PDL1 immunotherapy, and extracted the following data: publication year, source title, country/region, institution, and the total number of citations. The research design and area were classified independently by the authors. Subsequently, we carried out a bibliometric analysis to determine the trends and identify the major journals on anti-PD1/PDL1 immunotherapy. The authors analyzed the current research hotspots based on papers published in major journals from 2020 to 2021. These 100 papers were cited a total of 138,840 times, and the median number of citations was 899.5 (range: 341-7,983). "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer" by Topalian et al. had the highest number of citations (7,983 times). New England Journal of Medicine had the highest number of top-cited papers (40 papers), average citations per paper (1,558.3 citations), and rate of top-cited papers (65.6%). Authors from the USA contributed most of the papers (76 papers). Lung cancer (30 papers, 46,422 citations) and melanoma (20 papers, 30,881 citations) were the most cited research areas. In summary, anti-PD1/PDL1 has become standard treatment for various cancer, while adjuvant anti-PD1/PDL1 therapy is currently a research hotspot. New England Journal of Medicine was identified as the most influential journal in this area. Non-small cell lung cancer and melanoma are the most well-studied cancers, while nivolumab and pembrolizumab are the most commonly investigated anti-PD1/PDL1 antibodies. Further studies are warranted to identify effective predictive biomarkers or models, clarify the molecular mechanism of combined therapy, and establish optimal therapeutic strategies. This study may assist researchers in obtaining a comprehensive impression of the landscape and current trends in anti-PD1/PDL1 immunotherapy and gain inspiration to conduct further studies.

Keywords: PD1/PDL1; bibliometric analysis; clinical trials; immunotherapy; lung cancer; melanoma; tumor mutation burden.

Figure 1

(A) Time of publication and distribution of citations of the 100 most cited papers on anti-PD1/PDL1 immunotherapy. (B) Total number of top-cited papers and average citations per paper in major journals. PD1, programmed cell death 1; PDL1, programmed cell death 1 ligand 1. N. Engl. J. Med., New England Journal of Medicine; JAMA, Journal of the American Medical Association; JAMA Oncol., JAMA Oncology; J. Clin. Oncol., Journal of Clinical Oncology; Lancet Oncol., Lancet Oncology.

Figure 2

(A) Network visualization map of inter-country/-regional collaboration. (B) Total number of top-cited papers and average citations per paper according to the countries of corresponding authors. MCP, multiple-country publications; SCP, single-country publications.

Figure 3

(A) Network visualization of the countries/regions for the 100 most cited papers according to the average year of publication. (B) Network visualization of institutions for the 100 most cited papers according to the average year of publication. (C) Network visualization of authors with at least 2 of the 100 most cited papers according to cluster analysis. The circle size represents the number of articles included in the 100 most cited articles; the width of the curved line represents the strength of the connection; and the distance between two nodes approximates the relatedness.

Figure 4

(A) Distribution of publication time and citations of papers on cancers. The node size represents the number of publications; the color represents the average citations of the papers. (B) The relationship between cancers and anti-programmed cell death 1/programmed cell death 1 ligand 1 (anti-PD1/PDL1) antibodies. The node size represents the number of publications; the color represents the average year of publication. Atezoliz, atezolizumab; Avel, avelumab; Durval, durvalumab; H&N SCC, head and neck squamous cell cancer; Nivol, nivolumab; Other, lambrolizumab, cemiplimab, or pidilizumab; Pembroliz, pembrolizumab. (C) The relationship between cancers, anti-PD1/PDL1 antibodies, and research types for the 100 most cited papers. (D) Chordal graph of approved indications of anti-PD1/PDL1 antibodies. BCC, basal cell cancer; CC, cervical cancer; cHL, classical Hodgkin lymphoma; CRC, colorectal cancer; CSCC, cutaneous squamous cell cancer; EC, esophageal cancer; EMC, endometrial cancer; GC, gastric cancer; HCC, hepatocellular cancer; HNSCC, head and neck squamous cell cancer; MCC, Merkel cell cancer; MPM, malignant pleural mesothelioma; NSCLC, non-small cell lung cancer; PMBCL, primary mediastinal large B-cell lymphoma; RCC, renal cell cancer; SCLC, small-cell lung cancer; TNBC, triple-negative breast cancer; UC, urothelial cancer.

Figure 5

(A) Network visualization of keywords from the 100 most cited papers according to the average year of publication. (B) Network visualization of keywords from papers published in major journals from 2020 to 2021 according to cluster analysis. The circle size represents the number of articles included in the 100 most cited articles; the width of the curved line represents the link strength; and the distance between two keywords approximates the relatedness of the nodes. NSCLC, non-small cell lung cancer.