Mutational spectrum of TP53 gene correlates with nivolumab treatment efficacy in advanced gastric cancer (TP53MUT study)

Br J Cancer. 2023 Oct;129(6):1032-1039. doi: 10.1038/s41416-023-02378-9. Epub 2023 Aug 2.

Abstract

Background: Although nivolumab has a high efficacy, reliable biomarkers are needed to predict the efficacy. We evaluated the nivolumab efficacy according to the TP53 mutation in advanced gastric cancer patients enrolled in the GI-SCREEN project.

Methods: Sequence data of tumour specimens and clinicopathological information of 913 patients with advanced gastric cancer who were enrolled between April 2015 and March 2017 were obtained from the GI-SCREEN database. The follow-up information of 266 patients treated with nivolumab was also provided.

Results: Among 266 patients treated with nivolumab, the objective response rate (ORR) of TP53 wild type (wt) patients (24.6%) was higher than that of TP53 mutant patients (14.8%). Among TP53 mutant patients, the ORR of the frameshift type tended to be higher than the transition and transversion type (23.1%, 13.6%, and 13.0%, respectively). The median progression-free survival (PFS) was statistically longer in TP53 wt patients than in mutant patients (3.3 vs 2.1 months, HR 1.4, 95% CI 1.1-1.9). Among TP53 mutant patients, PFS was statistically longer in the frameshift type than in the transversion type.

Conclusion: Nivolumab showed better efficacy in TP53 wt patients than in mutant patients. Among TP53 mutant patients, the frameshift type may have efficacy from nivolumab treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Immunological* / therapeutic use
  • Genes, p53
  • Humans
  • Mutation
  • Nivolumab / therapeutic use
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Nivolumab
  • Antineoplastic Agents, Immunological
  • TP53 protein, human
  • Tumor Suppressor Protein p53

Associated data

  • UMIN-CTR/UMIN000016344