Actionable molecular alterations in advanced gynaecologic malignancies: updated results from the ProfiLER programme

Eur J Cancer. 2019 Sep;118:156-165. doi: 10.1016/j.ejca.2019.06.017. Epub 2019 Jul 24.

Abstract

Objectives: The objectives of this study were to identify actionable genomic alterations in the gynaecological subpopulation of the ProfiLER programme and to report clinical efficacy of recommended targeted treatment (RTT).

Methods: The ProfiLER programme (NCT01774409) is a multicentric prospective trial aiming to implement molecular profiling in patients with advanced refractory cancers. In this programme, tumour DNA is analysed by targeted next-generation sequencing (69 genes) and by whole genome array comparative genomic hybridisation. Clinical cases and genomic profiles are presented in a dedicated molecular tumour board to guide treatment strategies. We report here an analysis of patients with gynaecological cancers included in this trial.

Results: From February 2013 to February 2017, 309 patients with gynaecologic cancer were included; 279 (90%) had sufficient quality, and 131 patients (42.4%) had at least one actionable genomic alteration in cancer cells. Four alterations were shared by at least 3% of the patients: 27 (9.7%) PIK3CA mutations, 15 (5.4%) KRAS mutations, 11 (3.9%) ERBB2 amplifications and 9 (3.2%) CDKN2A deletions. Forty-one treatments were initiated among 39 patients (12.6% of the screened population): 8 (20%) had a partial response, and other 10 (24%) had a stable disease. The median progression-free survival was 2.7 months. The median overall survival was 15.6 months for patients who received a RTT.

Conclusion: Molecular profiling identified actionable alterations in 42.4% of patients with advanced refractory gynaecologic cancer, but only 12.6% were treated with a RTT. Among them, 46% derived clinical benefit (5.8% of the screened population).

Keywords: Gynaecologic cancer; Molecular targeted agents; Next-generation sequencing; Precision medicine; aCGH.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Clinical Decision-Making
  • Comparative Genomic Hybridization
  • Disease Progression
  • Female
  • France
  • Gene Amplification
  • Gene Deletion
  • Gene Expression Profiling*
  • Genetic Predisposition to Disease
  • Genital Neoplasms, Female / genetics*
  • Genital Neoplasms, Female / mortality
  • Genital Neoplasms, Female / pathology
  • Genital Neoplasms, Female / therapy
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged
  • Mutation
  • Patient Selection
  • Phenotype
  • Predictive Value of Tests
  • Progression-Free Survival
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Transcriptome*
  • Whole Genome Sequencing

Substances

  • Biomarkers, Tumor