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Published on: July 25, 2020
Phase II genomics study of ixabepilone as neoadjuvant treatment for breast cancer
José Baselga1, Milvia Zambetti, Antoni Llombart-Cussac
1Vall d'Hebron University Hospital, Barcelona, Spain. jbaselga@vhebron.net
Purpose:
This phase II study evaluated the efficacy and safety of ixabepilone as neoadjuvant therapy for invasive breast cancer not amenable to breast conservation surgery. Gene expression studies were undertaken using genes that were identified as potentially associated with sensitivity/resistance to ixabepilone in prior preclinical investigations.
Patients And Methods:
Patients with invasive breast cancer >or= 3 cm were eligible. Ixabepilone 40 mg/m(2) was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle for four or fewer cycles.
Results:
One hundred sixty-one patients were treated. The overall complete pathologic response (pCR) rate was 18% in breast and 29% in estrogen receptor (ER) -negative patients. Gene expression data were available for 134 patients. ER gene expression (ER1) was inversely related to pCR in breast and had a positive predictive value (PPV) of 37% and negative predictive value (NPV) of 92%. A 10-gene penalized logistic regression (PLR) model developed from 200 genes predictive of ixabepilone sensitivity in preclinical experiments included ER and tau and had higher PPV (45%) and comparable NPV (89%) to ER1. Grade 3 to 4 adverse events (AEs) were reported for 32% of patients. Except for neutropenia and leukopenia, all grade 3 to 4 AEs occurred in
Results:
indicate an inverse relation between ER expression levels and ixabepilone sensitivity. Neoadjuvant ixabepilone demonstrated promising activity and a manageable safety profile in patients with invasive breast tumors.
Insights
Neoadjuvant ixabepilone shows promise for invasive breast cancer, with estrogen receptor (ER) status and a 10-gene model predicting treatment response. This therapy offers a manageable safety profile for patients ineligible for breast conservation.
Area of Science:
- Oncology
- Pharmacogenomics
- Breast Cancer Research
Background:
- Invasive breast cancer often requires neoadjuvant therapy for patients not candidates for breast-conserving surgery.
- Ixabepilone, a microtubule inhibitor, has shown potential in breast cancer treatment.
- Gene expression profiling can identify biomarkers for drug sensitivity and resistance.
Purpose of the Study:
- To evaluate the efficacy and safety of ixabepilone as neoadjuvant therapy for invasive breast cancer.
- To explore gene expression patterns associated with ixabepilone sensitivity or resistance.
Main Methods:
- A phase II study administered ixabepilone (40 mg/m(2)) intravenously every 21 days to 161 patients with invasive breast cancer (>= 3 cm).
- Gene expression analysis was performed on samples from 134 patients.
- A 10-gene penalized logistic regression (PLR) model was developed to predict ixabepilone response.
Main Results:
- The overall complete pathologic response (pCR) rate was 18%, and 29% in estrogen receptor (ER)-negative patients.
- ER gene expression was inversely related to pCR (PPV 37%, NPV 92%).
- A 10-gene PLR model, including ER and tau, showed higher PPV (45%) and comparable NPV (89%) for predicting pCR.
Conclusions:
- Estrogen receptor (ER) expression, microtubule-associated protein tau, and a 10-gene PLR model are predictors of ixabepilone-induced pCR.
- Neoadjuvant ixabepilone demonstrates promising activity and a manageable safety profile in this patient population.
- ER expression levels correlate inversely with ixabepilone sensitivity.
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