Eri-001 Trial: Eribulin, An Effective and Safe Therapeutic Option in Heavily Pre-treated patients with Advanced Breast Cancer Treatment

3 Apr, 20

Introduction

Eribulin mesylate is currently approved in the EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease.

Aim

To investigate the efficacy and tolerability of eribulin as second or further-line chemotherapy in women affected by locally advanced unresectable or MBC

Patient Profile

N=137
Patients with locally advanced unresectable or MBC received eribulin as second or further line of treatment
Cytological or histologically confirmed diagnosis of locally advanced (unresectable) or MBC
Age ≥18 years, administration of at least one cycle of eribulin until disease progression
Unacceptable toxicity or patient refusal, availability of clinical-pathological
Radiological and laboratory parameters before eribulin treatment (baseline)
Response evaluation and survival data
Prior anthracycline and taxane-based chemotherapy in the adjuvant or metastatic setting

Table 1: Baseline Characteristics

Characteristics	Total n=137	%
Age (median) Range	58.1
Age, years
>70	22	16.1
<70	115	83.9
ECOG PS
0–1	133	97.1
2	4	2.9
Menopausal status
Premenopausal	38	27.7
Postmenopausal	99	72.3
Histology
Invasive lobular carcinoma	27	19.7
Invasive ductal carcinoma	104	75.9
Invasive ductal-lobular carcinoma	6	4.4
Grading*
Grades1–2	68	49.6
Grade3	69	50.4
Hormone receptor status*
ER and/or PgR negative	26	19
ER and/or PgR positive	111	81
*HER2* status*
Negative	111	81
Positive	26	19
Molecular subtypes
Luminal A	20	14.6
Luminal B Her2 positive	18	13.1
Luminal B Her2 negative	74	54
HERr2-like	7	5.1
Triple-negative	18	13.1
Stage at diagnosis
IA	18	13.1
IIA	44	32.1
IIB	13	9.5
IIIA	28	20.4
IIIB	1	0.7
IIIC	13	9.5
IV	20	14.6
Site of metastases
Visceral	67	48.9
Visceral + bone	64	46.7
Bone alone	6	4.4
Surgery (primary tumour)
Yes	126	92
No	11	8
Adjuvant chemotherapy
Yes	80	58.4
No	57	41.6
Adjuvant trastuzumab	18	13.1
Adjuvant hormonal therapy
Yes	77	56.2
No	60	43.8
Number of prior chemotherapy for advanced disease
1	22	16.1
2	52	38
3	27	19.7
≥4	36	26.2
Median (range)	4 (1–7)	–
Previous chemotherapy for MBC
Anthracyclines	54	35
Taxanes	120	87.5
Capecitabine	89	65
Vinorelbine	88	64.2
Gemcitabine	34	24.8
Previous hormonal therapy for advanced disease	95	66.4
Eribulin cycles administered, median(range)	5 (1–24)	–

Methods

The final analysis included 137 patients with locally advanced unresectable or MBC treated with eribulin monotherapy in different lines of therapy to evaluate its safety profile, activity, and efficacy

Patients treated at 13 different centers in the Campania region (Italy), according to current drug indications, were analysed
Progression-free survival (PFS) was defined as the time elapsed between the first eribulin dose to the detection of disease progression or death for any cause
Differences in PFS according to clinical parameters or line of treatment were evaluated by the log-rank test and described by the Kaplan-Meier method
Cox proportional hazards model was applied to multivariate survival analysis,

Results

Efficacy

Eribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy
The overall RR and DCR were 17.5% and 64%

Figure 1: Overall DCR and RR according to lines of treatment

Table 2: Tumour response with eribulin treatment in patients metastatic breast cancer

Response	All patients (%)	Second line (%)	Third line (%)	Fourth line (%)	>4th line (%)
Complete response	–
Stable disease	46.7	36.4	44.2	55.5	50
Partial response	17.5	13.6	21.1	14.8	16.7
Progression disease	35.8	50	34.6	29.6	33.3
Disease control rate	64.2	50	65.4	70.4	66.7

The longer median PFS was recorded in patients treated with eribulin in the third line (6.3 months)
- eribulin in second-line =5.7 months
- eribulin in fourth line= 4.5 months
- eribulin in subsequent lines = 4.0 months

Subgroup analysis results showed that

HER2 negative patients appeared to benefit from treatment with eribulin
- HER2-positive breast cancer patients displayed a shorter mPFS (4.2 vs 5.4 months, respectively)
No significant difference in terms of mPFS was found between the various BC subtypes
In elderly patients (>70 years), mPFS was 6.4 months and experienced only mild drug toxicity

Adverse events

Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable
Neutropenia was the most common grades 3–4 haematological adverse event (12.4%)
Grades 3–4 toxicities were neutropaenia and neurotoxicity

Conclusion

Eribulin was shown to be an effective and safe therapeutic option for second and further lines of treatment in patients with advanced BC
The data supports its use in daily clinical practice

Reference

ESMO Open 2017;2: e000176. doi:10.1136/esmoopen-2017-000176