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Anti-PD-1/anti-PD-L1 immunotherapy versus docetaxel for previously treated advanced non-small cell lung cancer: a systematic review and meta-analysis of randomised clinical trials
  1. Allan Ramos-Esquivel1,
  2. Alicia van der Laat2,
  3. Raquel Rojas-Vigott2,
  4. Melissa Juárez1,
  5. Luis Corrales-Rodríguez3
  1. 1Departamento de Oncología Médica, Hospital San Juan de Dios, Universidad de Costa Rica, San José, Costa Rica
  2. 2Departamento de Oncología Médica, Hospital México, San José, Costa Rica
  3. 3Department of Medical Oncology, Centro de Investigación y Manejo del Cáncer CIMCA, San José, Costa Rica
  1. Correspondence to Dr Allan Ramos-Esquivel; allan.ramos{at}ucr.ac.cr

Abstract

Background To compare the efficacy and toxicity of anti-programmed cell death receptor 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) versus docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC).

Materials and methods Phase III randomised clinical trials (RCTs) were identified after systematic review of databases and conference proceedings. A random-effect model was used to determine the pooled HR for overall survival (OS), progression-free survival (PFS) and duration of response. The pooled OR for overall response and treatment-related side effects were calculated using the inverse-variance method. Heterogeneity was measured using the τ2 and I2 statistics.

Results After the systematic review, we included four phase III RCTs (n=2737) in this meta-analysis. The use of anti-PD-1/anti-PD-L1 agents (atezolizumab, nivolumab and pembrolizumab) was associated with better OS in comparison with docetaxel alone (HR: 0.69; 95% CI 0.63 to 0.75; p<0.00001). Similarly, the PFS and duration of response was significantly longer for patients receiving immunotherapy (HR: 0.85; 95% CI 0.75 to 0.96; p=0.007 and HR:0.32; 95% CI 0.24 to 0.43; p<0.00001, respectively) versus single agent chemotherapy. The overall response rate was also higher for patients who received any anti-PD-1/anti-PD-L1 therapy in comparison with docetaxel (OR: 1.77; 95% CI 1.26 to 2.50; p=0.001). Regarding treatment-related side effects grade 3 or higher, patients who received immunotherapy experienced less events than patients allocated to docetaxel (OR: 0.19; 95% CI 0.12 to 0.30; p<0.00001)

Conclusion The use of anti-PD-1/anti-PD-L1 therapy in patients with progressive advanced NSCLC is significantly better than the use of docetaxel in terms of OS, PFS, duration of response and overall response rate.

  • non-small-cell lung cancer
  • atezolizumab
  • pembrolizumab
  • nivolumab
  • meta-analysis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors All authors had full access to all the data in the study and take responsibility for the integrity and accuracy of the data analysis. All authors contributed to the study concept and design. All authors read and approved the final version of this manuscript.

  • Funding This work was partially supported by Roche (no grant number is applicable).

  • Competing interests None declared.

  • Patient consent None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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