Meta-analysis: high TMB tied to PFS benefit with checkpoint inhibitors

  • Zhu J & al.
  • Front Pharmacol
  • 1 Jan 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • High vs low tumor mutation burden (TMB) is associated with significant improvement in PFS but not OS with programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors vs chemotherapy.
  • Patients with high TMB show significant PFS advantage with PD-1/PD-L1 inhibitors vs those with low TMB.

Why this matters

  • TMB may be a preferable biomarker to select patients for PD-1/PD-L1 inhibitors.

Study design

  • Meta-analysis of 8 studies including 2661 patients with cancer treated with PD-1/PD-L1 inhibitors or chemotherapy.
  • Funding: National Natural Science Foundation of China; Natural Science Foundation of Guangdong Province, China.

Key results

  • In the patients treated with PD-1/PD-L1 inhibitors vs chemotherapy, those with:
    • high TMB had significant PFS advantage (pooled HR, 0.66; 95% CI, 0.50-0.88; P=.004)
    • low TMB had no significant difference in PFS (pooled HR, 1.38; 95% CI, 0.82-2.31; P=.229).
    • no significant difference in OS was observed in patients with high (pooled HR, 0.73; 95% CI, 0.50-1.08; P=.114) or low TMB (pooled HR, 1.00; 95% CI, 0.80-1.24; P=.970).
  • High vs low TMB was associated with significant PFS benefit in patients treated with PD-1/PD-L1 inhibitors (HR, 0.47; 95% CI, 0.35-0.63; P=.000).

Limitations

  • Most of the included studies evaluated non-small cell lung cancer or bladder cancer, findings may not be generalizable to other cancers.

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