Tumor PD-L1 expression and Nivolumab efficacy in the treatment of cancer: a meta-analysis of phase III randomized clinical trials

Conference paper

Salah Eddine El Herrag, Meghit Boumediene Khaled
Biosciences 2019 – Biotechnology and Cancer, 3rd International Conference on Biotechnology and Cancer (ICBC), the Higher School of Biological Sciences of Oran, 2019 Dec 7, p. 106

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APA Click to copy
El Herrag, S. E., & Khaled, M. B. (2019). Tumor PD-L1 expression and Nivolumab efficacy in the treatment of cancer: a meta-analysis of phase III randomized clinical trials. In 3rd International Conference on Biotechnology and Cancer (ICBC) (p. 106). the Higher School of Biological Sciences of Oran.

Chicago/Turabian Click to copy
El Herrag, Salah Eddine, and Meghit Boumediene Khaled. “Tumor PD-L1 Expression and Nivolumab Efficacy in the Treatment of Cancer: a Meta-Analysis of Phase III Randomized Clinical Trials.” In 3rd International Conference on Biotechnology and Cancer (ICBC), 106. Biosciences 2019 – Biotechnology and Cancer. the Higher School of Biological Sciences of Oran, 2019.

MLA Click to copy
El Herrag, Salah Eddine, and Meghit Boumediene Khaled. “Tumor PD-L1 Expression and Nivolumab Efficacy in the Treatment of Cancer: a Meta-Analysis of Phase III Randomized Clinical Trials.” 3rd International Conference on Biotechnology and Cancer (ICBC), the Higher School of Biological Sciences of Oran, 2019, p. 106.

BibTeX Click to copy

@inproceedings{el2019a,
  title = {Tumor PD-L1 expression and Nivolumab efficacy in the treatment of cancer: a meta-analysis of phase III randomized clinical trials},
  year = {2019},
  month = dec,
  day = {7},
  organization = {the Higher School of Biological Sciences of Oran},
  pages = {106},
  series = {Biosciences 2019 – Biotechnology and Cancer},
  author = {El Herrag, Salah Eddine and Khaled, Meghit Boumediene},
  booktitle = {3rd International Conference on Biotechnology and Cancer (ICBC)},
  month_numeric = {12}
}

Abstract
Introduction and aims:
Nivolumab is a fully-humanized IgG4 monoclonal antibody that binds to the PD-1 receptor expressed by activated T-cells blocking thus the immune checkpoint and activating an immune response to tumor cells [1]. We conducted a meta-analysis with the aim of investigating the effect of tumor PD-L1 expression on the efficacy of Nivolumab in the treatment of different types of cancer.
Materials and Methods:
The meta-analysis was performed in conformity with the Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) statement [2]. Phase III randomized clinical trials were identified through a systematic literature search over PubMed, Cochrane, and the clinicaltrials.gov databases up until August 15th, 2019. The included studies provided hazard ratios for overall survival (OS), progression-free survival (PFS), and odds ratios for objective response rates (ORR). The generic inverse variance method was used for the pooled analysis. The statistical analyses were carried out with the R statistical program (version 3.6) [3].
Results and Discussion:
Thirteen phase III randomized controlled trials were included involving 7,371 cancer patients. The trials examined the efficacy of Nivolumab in patients with melanoma [4–6], non-small cell lung cancer (NSCLC) [7–11], renal cell carcinoma (RCC) [12,13], Squamous Cell Carcinoma of the Head and Neck (SCCHN) [14,15], and gastric cancer (GC) [16] with PD-L1 tumor expression levels < 1%, ≥ 1%, < 5%, ≥ 5%, < 10%, and ≥ 10%. The hazard ratios for overall survival among patients with PD-L1 < 1% were (0.71; 95% CI 0.58 ;0.87) for melanoma, (0.77; 95% CI 0.61; 0.97) for NSCLC, (0.89; 95% CI 0.54; 1.45) for SCCHN, (0.98; 95% CI 0.56; 1.72) for RCC, and (0.76; 95% CI 0.49; 1.18) for GC. Among patients with PD-L1 ≥ 10%, the pooled HRs were (0.65; 95% CI 0.46; 0.92) for melanoma, (0.43; 95% CI 0.31; 0.60) for NSCLC, and (0.56; 95% CI 0.31; 1.01) for SCCHN. Similar pattern was observed for PFS. The summary of HRs for the PD-L1 <1% subgroup were (0.54; 95% CI 0.40; 0.73) for melanoma, (0.75; 95% CI 0.44; 1.29) for NSCLC, (0.39; 95% CI 0.09; 1.67) for SCCHN, and (1.00; 95% CI 0.80; 1.26) for RCC. Among patients with PD-L1 ≥ 10%, the pooled HRs were (0.43; 95% CI 0.28; 0.65) for melanoma, (0.54; 95% CI 0.40; 0.73) for NSCLC.
Conclusion and Perspective:
According to our findings, patients with higher tumor PD-L1 levels have benefited the most from treatment with Nivolumab where the overall survival and progression-free survival was longer for this subgroup compared with patients with lower PD-L1 levels. We, therefore, suggest that tumor PD-L1 expression may be taken into consideration when assigning Nivolumab for the treatment of the investigated cancers in our study.
Keywords: Neoplasms; Nivolumab; PD-L1; meta-analysis.

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Poster ICBC-19