Effect of region on the Outcome of Patients Receiving PD-1/PD-L1 Inhibitors for Advanced Cancer

Int Immunopharmacol. 2019 Sep:74:105709. doi: 10.1016/j.intimp.2019.105709. Epub 2019 Jul 2.

Abstract

Background: Regional differences were associated with cancer incidence and mortality. However, the correlation between regional differences and cancer immunotherapy efficacy was still not evaluated. In this study, we performed a meta-analysis to investigate whether regional differences play a role in efficacy of PD-1/L1 inhibitors in cancer patients.

Methods: A meticulous review of relevant randomized controlled trials that were sourced from the PubMed, Embase and MEDLINE databases. Overall survival (OS) and progression-free survival (PFS) were the primary outcome and secondary outcome in our study, respectively. We also assessed difference on the hazard ratio (HR) between European and North American groups.

Results: A total of 14 randomized clinical trials including 9387 patients were finally eligible for meta-analysis in our study. With respect to the pooled HR in treatment with PD-1/L1 inhibitors, North American patients presented OS as 0.60 (95% CI 0.53 to 0.67), and PFS as 0.49 (95% CI 0.40 to 0.59), whereas European patients presented OS as 0.76 (95% CI 0.62 to 0.90), and PFS as 0.58 (95% CI 0.44 to 0.72), relative to their corresponding control groups. OS efficacy thus varied significantly (Pheterogeneity = 0.028) between North American and European patients when treated with PD-1/L1 inhibitors.

Conclusions: Our findings were very surprising especially considering the higher prevalence of cancer in Europe. Although PD-1/L1 inhibitors improved OS and PFS in both North American and European patients compared with controls, the magnitude of benefit was region-dependent. North American patients can benefit more from PD-1/L1 inhibitors than European patients. More researches were urgently demanded to explore its potential molecular mechanisms.

Keywords: Europe; North America; Overall survival; PD-1/L1 inhibitors; Regional difference.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors
  • Europe / epidemiology
  • Humans
  • Immunotherapy / methods*
  • Neoplasms / drug therapy
  • Neoplasms / epidemiology*
  • Neoplasms / mortality
  • North America / epidemiology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Randomized Controlled Trials as Topic
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor