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

Table of Content

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