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29P - Plasma ESR1 mutations and outcome to first-line chemotherapy with bevacizumab and paclitaxel in patients with advanced ER-positive/HER2-negative breast cancer

Abstract

Background

ESR1 mutations have been identified as a mechanism for endocrine resistance and occur frequently after treatment with aromatase inhibitors. Here, we assessed whether the combination of bevacizumab/paclitaxel yields sufficient anti-tumor activity to justify further exploration in advanced ER+/HER2- breast cancer patients with acquired ESR1 mutations in circulating tumor DNA (ctDNA).

Methods

We assessed ESR1 mutations in baseline plasma samples from patients who started with paclitaxel/bevacizumab (AT arm) in the phase II ATX study (BOOG-2006-06) and who were previously treated with an aromatase inhibitor in the adjuvant and/or metastatic setting. Baseline plasma samples from 44 patients were analyzed for ESR1 mutations by next generation sequencing. The primary objective was to assess the progression-free survival (PFS) rate at six months. We applied a two-stage design with α=0.05, β=0.20, P0=0.4 and P1=0.75 was applied, requiring at least 8 of 14 ESR1 mutant patients to be free of progression at 6 months on paclitaxel/bevacizumab. For P0, we assumed a 6-months PFS rate of 40% on fulvestrant, which is a commonly used treatment in these patients. Secondary outcomes were objective response rate (ORR) and overall survival (OS).

Results

ESR1 mutations were detected in 20 (45%) baseline samples. The 6-month PFS rate was 83% for ESR1 wild-type patients versus 85% for ESR1 mutant patients (17/20). The median PFS was 8.6 months [95% confidence interval (CI), 8.2-9.1] for ESR1 wild-type patients versus 8.1 months [95% CI, 7.2-9.0] for ESR1 mutant patients [log rank P=0.807]. The ORR was higher in ESR1 wild-type patients than in ESR1 mutant patients [75% vs 50%] although this percentage was not significant [P=0.052]. The median OS was 24.8 months [95% confidence interval (CI), 17.4-32.2] for ESR1 wild-type patients versus 20.7 months [95% CI, 2.1-39.3] for ESR1 mutant patients [log rank P=0.443].

Conclusions

This explorative study indicates that in advanced breast cancer patients with ESR1 mutations in plasma it is worthwhile to start bevacizumab/paclitaxel as further treatment.

Legal entity responsible for the study

Erasmus MC Cancer Institute.

Funding

Dutch Cancer Society.

Disclosure

All authors have declared no conflicts of interest.

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