Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials

J Immunother Cancer. 2019 Jun 25;7(1):159. doi: 10.1186/s40425-019-0636-7.

Abstract

Recent phase 1-2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1-5/3-5 AEs were 74.1%/29.6, 54.2%/17.4, 92.3%/24.5, 96.8%/16.1, 91.2%/42.8, and 100%/87.9% for pembrolizumab, nivolumab, JS001, camrelizumab, chemotherapy and camrelizumab+chemotherapy, respectively, which suggested that nivolumab and pembrolizumab exhibited the optimal safety regarding grade 1-5 AEs whereas camrelizumab and nivolumab regarding grade 3-5 AEs. As second- or later-line therapy, ORR was higher with camrelizumab (34.1%), followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%); whereas ORR with first-line nivolumab reached 40%. Additionally, first-line camrelizumab+chemotherapy achieved a dramatically higher ORR than that with chemotherapy alone (90.9% vs. 64.1%). Pooled ORR was 28.4 and 17.4% for PD-L1-positive and PD-L1-negative patients, respectively (P = 0.11). Here, we represent preliminary evidence for the comparative safety and efficacy of existing anti-PD-1 agents with/without chemotherapy in RM-NPC, which indicated that camrelizumab has the least toxicity profile and merits future investigation. Our findings might provide insights into the future design of immunotherapy trials in RM-NPC.

Keywords: Anti-PD-1; Chemotherapy; Combination therapy; Efficacy; Nasopharyngeal carcinoma; Predictive biomarker; Safety profiles.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Clinical Trials as Topic
  • Humans
  • Molecular Targeted Therapy
  • Nasopharyngeal Carcinoma / diagnosis
  • Nasopharyngeal Carcinoma / drug therapy*
  • Nasopharyngeal Carcinoma / mortality
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Odds Ratio
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Programmed Cell Death 1 Receptor