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 » Introduction
 » Procedure
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 3  |  Page : 297-298
 

Eribulin mesylate in Indian patients: A single center experience


1 Department of Medical Oncology, Sri Shankara Cancer Hospital and Research Centre, Bengaluru, Karnataka, India
2 Department of Medical Oncology, HCG Bangalore Institute of Oncology Speciality Centre, Bengaluru, Karnataka, India
3 Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Date of Web Publication18-Feb-2016

Correspondence Address:
S Patil
Department of Medical Oncology, HCG Bangalore Institute of Oncology Speciality Centre, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.176735

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 » Abstract 

Background: Eribulin mesylate is the latest addition in the armamentarium of management of metastatic breast cancer (MBC) with a unique mechanism of action. Although the multicentric EMBRACE trial suggests significant overall survival benefit from this novel drug, its effectiveness in Indian population is yet to be evaluated. Materials And Methods: Presented here is a single center experience of eight patients who were administered eribulin for MBC. Patients had received a median of 3 prior chemotherapies before eribulin administration. The median dose of eribulin therapy was 5 cycles (range: 2–6 cycles). Results: The objective response rate was 75% (CR in one and PR in five out of eight patients). Response was seen across all subtypes of patients. Eribulin was well tolerated. No serious adverse events were reported. Conclusion: Eribulin conferred good response rates with satisfactory tolerability profile in Indian patients. Its use in earlier lines and in combination with other drugs may achieve deeper and longer responses.


Keywords: Eribulin, metastatic breast cancer, overall survival


How to cite this article:
Thippeswamy R, Patil S, Shashidara H P, Satheesh C T, Vittal H, Mishra S. Eribulin mesylate in Indian patients: A single center experience. Indian J Cancer 2015;52:297-8

How to cite this URL:
Thippeswamy R, Patil S, Shashidara H P, Satheesh C T, Vittal H, Mishra S. Eribulin mesylate in Indian patients: A single center experience. Indian J Cancer [serial online] 2015 [cited 2019 Aug 20];52:297-8. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/297/176735



 » Introduction Top


Treatment guidelines for managing metastatic breast cancer (MBC) do not preferentially recommend any particular chemotherapeutic agent, neither as combination nor as monotherapy, in second line and later settings. Although capecitabine, gemcitabine and vinca alkaloids are popular choices in these patients, there is still a great unmet need of improving the response rates and quality of life, along with possibly providing overall survival benefits.

Eribulin mesylate is a structurally simplified synthetic analog of halichondrin B, which acts as a microtubule-destabilizing agent.[1] In addition, it exerts significant effects on epithelial-mesenchymal transition/mesenchymal-epithelial transition-related pathway components in human breast cancer cells, thereby delaying the metastasis.[2] The EMBRACE [3],[4] study (open-label, multicenter, international, randomized phase III trial), conducted in MBC patients in third line and later settings concluded that OS was significantly longer in the eribulin arm (13.2 months) as compared with the treatment of physician's choice arm (10.5 months) (P = 0.014; hazard ratio = 0.805; 95% confidence interval = 0.677, 0.958), with an acceptable tolerability profile.


 » Procedure Top


This single center retrospective case compilation and analysis was done in order to access the efficacy and tolerability of eribulin in Indian patient population at Sri Shankara Cancer Hospital and Research Centre, Bengaluru. Eight patients of breast cancer who were administered eribulin mesylate (at least 2 cycles) in the metastatic setting are discussed here. The median age of eight patients was 52 years (range: 36–60 years). One patient was premenopausal while the other seven were postmenopausal. Four of these cases were triple negative while 2 of them were HER-2 positive. Two of these eight patients were hormone positive while other six were hormone negative. All the patients had received taxane and anthracycline previously in adjuvant/neoadjuvant or advanced setting. 75% patients (6/8) had received gemcitabine-carboplatin combination, 50% patients (4/8) had received capecitabine while 38% patients (3/8) had received vinorelbine prior to eribulin. Patients had received a median of 3 prior chemotherapies before eribulin therapy. Furthermore, both the HER-2 positive patients had failed on targeted therapy before eribulin administration. The median dose of eribulin therapy was 5 cycles (range: 2–6 cycles).


 » Results Top


In regards to efficacy, complete response (CR) was observed in one patient while 63% patients (5/8) obtained a partial response (PR). The objective response rate (CR + PR) was 75%, which is higher than expected possibly because eribulin was used in relatively earlier lines for MBC in this analysis compared to EMBRACE study. Of the responders, 33% (2/6) were hormone positive, 66% (4/6) were hormone negative while 50% (3/6) were triple negative breast cancer patients. Furthermore, 25% patients (2/8) developed progressive disease despite eribulin therapy, which is slightly lower compared with EMBRACE study. Of the two HER-2 positive patients, one had PR and the other developed progressive disease. One out of the four triple negative patients obtained CR, and two had PR while the disease progressed in one of them.

Of the five patients who were benefitted with PR, one had cutaneous metastasis, one had locally advanced disease, two had lung metastasis and one had both cutaneous and lung metastasis prior to eribulin administration and the lesions diminished in size after eribulin therapy.

The patient who achieved CR was initially diagnosed in April 2013 as triple negative invasive ductal carcinoma of the breast with metastasis to lungs (T2 N0 M1). She underwent modified radical mastectomy, followed by docetaxel, anthracycline, cyclophosphamide regimen, 6 cycles from September 2013 to January 2014. PR was seen, but the disease relapsed in the form of brain metastasis in June 2014. Eribulin was started as a second line therapy in July 2014, and the patient received 6 cycles till November 2014. The lesion in the brain disappeared completely, [Figure 1] which commensurated with improvement in a clinical picture. The role of eribulin in brain metastasis needs to be evaluated further in clinical trials for complete understanding.
Figure 1: a) Computed tomography (CT) scan of brain prior to eribulin administration (June 2014) and, b) CT scan of brain after 6 cycles of eribulin (November 2014)

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With regards to safety, the drug was well tolerated by all the patients and the adverse events seen were consistent with the known adverse event profile of eribulin, most common being the neutropenia, fatigue, and nausea. No serious adverse events were reported.


 » Conclusion Top


Eribulin is an intravenous drug that requires no premedication, can be administered easily over 2–5 min and the patient need not get admitted to the hospital. Its tolerability appears to be satisfactory even as the 4th or 5th-line chemotherapeutic option. The reason for modest efficacy may be that the drug was administered in late lines, in the refractory settings, in the cases discussed here. Use of eribulin in earlier lines may be more beneficial to the patients and may provide us a more transparent measure of its efficacy. Combination with other drugs is probably necessary to achieve deeper and longer responses and may open newer avenues in the management of MBC, thereby addressing the unmet needs.

The limitations of this analysis are the retrospective observational design and fewer numbers of patients while the strength is that it analyses the experience of eribulin in a real world heterogeneous population, unlike clinical trials. Moreover, since the EMBRACE trial did not include any Indian patients, this analysis provides a measure of understanding the efficacy and safety of eribulin mesylate for the 1st time in Indian population.

 
 » References Top

1.
Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, et al. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther 2005;4:1086-95.  Back to cited text no. 1
    
2.
Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer 2014;110:1497-505.  Back to cited text no. 2
    
3.
Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): A phase 3 open-label randomised study. Lancet 2011;377:914-23.  Back to cited text no. 3
    
4.
Twelves C, Loesh D, Blum J, Vahdat L, Petrakova K, Durando X, et al. Updated survival analysis of a phase III study (EMBRACE) of eribulin mesylate versus treatment of physician's choice in subjects with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane. Cancer Res 2010;70 (24 Suppl): Abstract nr P6-14-18.  Back to cited text no. 4
    


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