Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

ePoster Display

256P - PI3K mutation is associated with reduced sensitivity to CDK4/6 inhibitors in metastatic breast cancer

Date

16 Sep 2021

Session

ePoster Display

Presenters

Keechilat Pavithran

Citation

Annals of Oncology (2021) 32 (suppl_5): S457-S515. 10.1016/annonc/annonc689

Authors

K. Pavithran1, H. Jayamohanan1, W.M. Jose1, S. Soman1, D.K. Vijaykumar2, P.S. Ariyannur3

Author affiliations

  • 1 Dept Of Medical Oncology, Amrita Institute of Medical Sciences and research centre, 682041 - Kochi/IN
  • 2 Surgical Oncology, Amrita Institute of Medical Sciences - AIMS Hospital, 682041 - Kochi/IN
  • 3 Biochemistry & Molecular Oncology, Amrita Institute of Medical Sciences, 682041 - Kochi/IN
More

Abstract 256P

Background

PI3K mutations contribute to endocrine resistance. PIK3CA mutation may be present de novo at the time of diagnosis or may be acquired later. The present study evaluated the incidence and distribution of de novo PIK3CA mutations in hormone receptor-positive / HER2-negative metastatic breast cancer (MBC) and its impact on clinical outcomes of patients treated with CDK4/6 inhibitors.

Methods

This was a retrospective study. All patients with MBC on endocrine therapy with CDK4/6 inhibitors whose initial tissue FFPE blocks were available were enrolled in this study. The genomic DNA was extracted and analysed using Therascreen® PIK3CA RGQ PCR Kit.

Results

36 patients were included in this study. The median age was 59 years (range 34-81). 21 (58.6%) patients were on palbociclib and 15 (41.4%) on ribociclib along with endocrine therapy. Of the 36 patients 17 (47.2%) were PIK3CA mutant (12 patients- exon 20 (70.5%); 5 had exon 9 (29.4%) mutation). The common amino acid substitutions in exon 9 were at codon 542 and 545 and exon 20 at 1047R. One patient had a double mutation on both exons 9 and 20. This patient had progression within 6 months of initiation of therapy. At 12 months, the overall response rate (ORR) in the non-mutant group was 26% (2 CR and 3 PR). 3 patients had stable disease and 11 patients (57.89%) had progressive disease (PD), of which 3 patients died in less than 1 year. Among the 17 patients with PIK3CA mutation, there were no complete or partial responders; only 1 patient had stable disease. The remaining 16 (94.1%) patients had PD, of which 5 patients succumbed to the disease in less than 12 months. PIK3CA mutation was associated with shorter progression-free survival (PFS) compared to PIK3CA wild type (18 versus 32.2 months, p-value 0.004) and shorter overall survival (OS) (41.7 versus 45 months, p value=0.772). The mean PFS was better in those with exon 9 mutation (22.2 months) than exon 20 ( 11.2months, p-value 0.4).

Conclusions

The incidence and type of PIK3CA mutation is similar to the data reported previously. The presence of de novo PI3K mutation confers a worse clinical outcome in HR-positive / HER2 negative metastatic breast cancer patients despite use of CDK4/6 inhibitors. The presence of de novo PIK3CA mutation should be assessed upfront.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings