FCGR3A-158 Polymorphism Predictive of Trastuzumab Efficacy in Breast Cancer

Share this content:
The FCGR3A-158 polymorphism may be predictive of trastuzumab efficacy in patients with early-stage ERBB2/HER2-positive breast cancer.
The FCGR3A-158 polymorphism may be predictive of trastuzumab efficacy in patients with early-stage ERBB2/HER2-positive breast cancer.

The FCGR3A-158 polymorphism may be predictive of trastuzumab efficacy in patients with early-stage ERBB2/HER2-positive breast cancer, with trastuzumab being less efficacious in those who are homozygous for the low-affinity allele, according to a study published in JAMA Oncology.1                                                 

Preclinical studies suggest that single nucleotide polymorphisms (SNP) in FCGR3A and FCGR2A may be associated with varying response to the anti-HER2 monoclonal antibody trastuzumab in patients with ERBB2/HER2-positive breast cancer.

To evaluate the effect of FCGR3A and FCGR2A SNPs on trastuzumab efficacy in the adjuvant treatment of ERBB2/HER2-positive breast cancer, investigators analyzed data from 1251 patients with surgically resected node-positive, early-stage disease who participated in the phase 3 NSABP (National Surgical Adjuvant Breast and Bowel Project B-31 trial; ClinicalTrials.gov Identifier: NCT00004067).

In NSAPB B-31, patients receive doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab weekly for 1 year.

After a median follow-up of 8.2 years, results showed that disease-free survival probability at 3, 5, and 8 years was 74% (95% CI, 71-79), 66% (95% CI, 62-71), and 58% (95% CI, 54-63) in patients who received chemotherapy alone, respectively. Among those who received chemotherapy and trastuzumab, disease-free survival was 86% (95% CI, 83-89), 82% (95% CI, 79-85), and 78% (95% CI, 74-81) at 3, 5, and 8 years, respectively.

Researchers found that adding trastuzumab significantly reduced the risk of relapse by 54% (hazard ratio [HR], 0.46; 95% CI, 0.37-0.57; P < .001).

RELATED: FDA Grants Priority Review to Ribociclib in HR+ Advanced Breast Cancer

Patients with genotypes FCB3A-158V/V or FCB3A-158V/F achieved greater benefit from trastuzumab (HR, 0.31; 95% CI, 0.22-0.43; P < .001) than patients who were homozygous for phenylalanine at this position (HR, 0.71; 95% CI, 0.51-1.01; P = .05).

In contrast with previous reports, the findings indicate that trastuzumab may be less efficacious in patients homozygous for the low affinity allele of FCGR3A. Additional studies are needed to validate these results.

Reference

  1. Gavin PG, Song N, Kim SR, et al. Association of polymorphisms in FCGR2A and FCGR3A with degree of trastuzumab benefit in the adjuvant treatment of ERBB2/HER2–positive breast cancer. JAMA Oncol. 2016 Nov 3. doi: 10.1001/jamaoncol.2016.4884 [Epub ahead of print]

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters



Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs