Postoperative adjuvant eribulin in high-risk patients with soft tissue sarcoma: A retrospective study of eight cases

Abstract

Background

The role of perioperative chemotherapy in localized soft tissue sarcomas (STS) remains controversial, particularly in older adult patients and those with considerable comorbidities who may not tolerate anthracycline-based regimens. Although eribulin has demonstrated efficacy and safety in advanced STS, its use as a postoperative adjuvant treatment has not been well documented.

Objective

To evaluate the feasibility, safety, and clinical outcomes of postoperative adjuvant eribulin administration in patients with localized STS, with a focus on older adults and patients with comorbidities.

Methods

We conducted a single-institution retrospective study of a case series of patients with localized STS who had undergone surgical resection with curative-intent, followed by postoperative adjuvant eribulin administration. Data on patient characteristics, treatment administration, adverse events, and oncological outcomes were obtained from the medical records. Adverse events were graded based on the Common Terminology Criteria for Adverse Events.

Results

Eight patients, most of whom were older adults or had substantial comorbidities, were included in the study. Postoperative eribulin therapy was initiated in all patients. Hematological toxicities, including neutropenia and leukopenia, were relatively common, but manageable with dose modification and supportive care. Non-hematological toxicities, such as peripheral neuropathy and dysgeusia, were generally mild to moderate. No treatment-related deaths or clinically significant cardiac adverse events were observed. Six patients remained continuously disease-free during follow-up, whereas two died of the disease.

Conclusions

Postoperative adjuvant eribulin therapy was feasible and well-tolerated in a high-risk population of patients with localized STS. Although its efficacy cannot be determined from this small case series, its favorable safety profile suggests that eribulin may be a viable treatment option for patients who are poor candidates for anthracycline-based perioperative chemotherapy. Further studies are warranted to clarify its role in perioperative treatment strategies for STS.

Keywords

soft tissue sarcoma eribulin adjuvant chemotherapy postoperative treatment older adult patients comorbidities

Introduction

Soft tissue sarcoma (STS) consists of a heterogeneous group of rare, malignant tumors, and complete surgical resection remains the keystone of curative treatment for localized disease. However, patients with high-risk pathological features continue to have high recurrence rates and disease-related mortality.¹

However, the role of perioperative chemotherapy in localized STS remains controversial. Several randomized trials and meta-analyses have suggested the modest benefit of anthracycline-based regimens in selected high-risk patients; however, consistent survival advantages have not been demonstrated.^2,3 Accordingly, perioperative chemotherapy is not universally recommended in current clinical practice guidelines, and its use is often individualized.⁴

Older patients and those with considerable comorbidities are major clinical challenges. Anthracycline-based chemotherapy, which is commonly used in the perioperative setting, may be poorly tolerated in this population due to concerns regarding cardio- and treatment-related toxicities.⁵ Consequently, perioperative systemic treatment options for these patients are limited, and evidence guiding clinical decision-making is scarce.

Eribulin mesylate is a microtubule dynamics inhibitor that has demonstrated efficacy in advanced and metastatic STS, and is generally considered to have a favorable cardiac safety profile.⁶ Despite its established role in the metastatic setting, no data are available regarding the use of eribulin as a perioperative or adjuvant treatment for localized STS.^4,7

Therefore, we conducted a retrospective case series study to evaluate the feasibility, safety, and clinical outcomes of postoperative adjuvant eribulin administration in patients with localized STS, with a focus on older adult patients and those with notable comorbidities. Furthermore, we discuss the potential implications of our findings for the development of perioperative treatment strategies in high-risk patients with STS.

Materials and methods

Study design and patients

In this single-institution, retrospective case series study, we reviewed the data of consecutive patients with localized STS who had undergone surgical resection with curative-intent followed by postoperative adjuvant chemotherapy with eribulin at Tochigi Cancer Center, Tochigi, Japan, between July 2018 and June 2024.

Patients who had received eribulin exclusively as a postoperative adjuvant treatment were eligible for inclusion. Those who had received eribulin for unresectable or metastatic disease at treatment initiation were excluded from the study. The decision to administer eribulin was made by a multidisciplinary sarcoma team, and was primarily based on the patient’s age, comorbidities, and their anticipated tolerability of anthracycline-based chemotherapy. Written informed consent for treatment was obtained from all patients as part of routine clinical practice. This study is reported as a case series and conforms to the CARE (CAse REport) guidelines.⁸ A completed CARE checklist has been provided as Supplemental file 1.

Data collection

Clinical data were retrospectively collected from the electronic medical records. The collected variables included age, sex, comorbidities, tumor location, histological subtype, surgical margin status, use of postoperative radiotherapy, number of eribulin treatment cycles, eribulin dosing schedule, treatment modifications, oncological outcomes, follow-up duration (months), and adverse events.

Adverse events were assessed throughout eribulin treatment and graded based on the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.⁹

Treatment protocol

Eribulin was administered intravenously according to institutional practice. The standard dosing schedule consisted of two consecutive weekly administrations, followed by a 1-week rest period (2-on/1-off schedule). Dose reductions, treatment delays, and supportive care, including the use of granulocyte colony-stimulating factors, were permitted at the discretion of the treating physician, based on the patient’s condition and treatment-related toxicity.

All patients were administered eribulin after surgical resection. Postoperative radiotherapy was also administered when clinically indicated, based on the tumor location, surgical margin status, and multidisciplinary discussion.

Outcome measures

The primary endpoints of this study were the feasibility and safety of postoperative adjuvant eribulin administration. Feasibility was evaluated based on treatment initiation, continuation, dose modification, and discontinuation due to adverse events.

The secondary endpoints included descriptively assessed oncological outcomes. Disease-free status, recurrence, and disease-related death were recorded based on clinical and radiological follow-up.

Statistical analysis

Given the small sample size and descriptive nature of this case series, no formal statistical comparisons were performed. Continuous variables are presented as medians and ranges, and categorical variables as counts. No formal sample size calculation was performed due to the descriptive and exploratory nature of this retrospective case series.

Ethics approval

This study was conducted at Tochigi Cancer Center, Tochigi, Japan. This retrospective case series was conducted using anonymized clinical data obtained from routine clinical practice. According to the institutional policy of Tochigi Cancer Center, retrospective studies using fully anonymized data are covered by the institutional comprehensive consent system and do not require individual Institutional Review Board approval. All patient data were fully de-identified prior to analysis. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2024).

Results

Patient characteristics

Eight patients who received postoperative adjuvant eribulin for STS were included in the analysis (Table 1). The cohort consisted predominantly of high-risk patients: six patients were aged ≥70 years, and the remaining two patients were younger but had significant comorbidities.

Table 1.

Patient demographics and clinical characteristics.

No.	Age	Sex	Histological type	Location	Surgical margin	Postoperative RT
1	54	Woman	Dedifferentiated liposarcoma	Retroperitoneum	R1	None
2	65	Woman	Myxoid liposarcoma	Thigh	R0	None
3	74	Man	Pleomorphic liposarcoma	Thigh	R0	None
4	76	Woman	Myxofibrosarcoma	Retroperitoneum	R1	50Gy/25Fr
5	77	Woman	Pleomorphic liposarcoma	Thigh	R0	None
6	78	Woman	Myxofibrosarcoma	Lower leg	R0	None
7	82	Man	Myxofibrosarcoma	Inguinal region	R0	None
8	84	Man	Myxofibrosarcoma	Thigh	R0	None

Abbreviations are RT: Radiation therapy, Fr: fraction.

Myxofibrosarcoma was the most common histological subtype (n = 4) followed by pleomorphic liposarcoma (n = 2). One patient each had myxoid and dedifferentiated liposarcoma. Tumors arose at various anatomical sites, including retroperitoneal and intraperitoneal locations. Details regarding the surgical margins and the use of postoperative radiotherapy are summarized in Table 1.

Eribulin administration and feasibility

Details of the comorbidities and the eribulin dosing schedule are presented in Table 2. Eribulin was administered as postoperative adjuvant chemotherapy in all patients. Treatment initiation was feasible in all patients, including those with cardiovascular disease or impaired organ function.

Table 2.

Patient comorbidities and details of eribulin administration.

No.	Comorbidities	Rationale for first-line eribulin use	Eribulin dosing schedule	No. of cycles administered	Adverse events
No.	Comorbidities	Rationale for first-line eribulin use	Eribulin dosing schedule	No. of cycles administered	Grade 1	Grade 2	Grade 3	Grade 4
1	None	Renal dysfunction after right nephrectomy	2-on/1-off schedule with peg-filgrastim	3	Anemia
2	Sick sinus syndrome	Cardiac dysfunction	2-on/1-off schedule with filgrastim	2		Anemia	Neutropenia
2	Hypertension	Cardiac dysfunction	2-on/1-off schedule with filgrastim	2		Anemia	Neutropenia
3	Diabetes mellitus	Age ≥70 years	2-on/2-off schedule with peg-filgrastim	3		Leukopenia	Neutropenia
	Hypertension					Leukopenia
	Dyslipidemia					Peripheral neuropathy
	Hyperuricemia					Peripheral neuropathy
4	Dyslipidemia	Age ≥70 years	2-on/2-off schedule with peg-filgrastim	3		Anemia	Leukopenia	Neutropenia
4	Dyslipidemia	Age ≥70 years	2-on/2-off schedule with peg-filgrastim	3		Dysgeusia	Leukopenia	Neutropenia
5	Dyslipidemia	Age ≥70 years	2-on/2-off schedule with peg-filgrastim	2		Anemia	Leukopenia
5	Glaucoma	Age ≥70 years	2-on/2-off schedule with peg-filgrastim	2		Anemia	Neutropenia
6	Diabetes mellitus	Age ≥70 years	2-on/1-off schedule with peg-filgrastim	5	Dysgeusia	Anemia	Neutropenia
	Hypertension					Leukopenia
	Dyslipidemia					Leukopenia
7	DCM	Age ≥70 years (DCM)	2-on/2-off schedule with peg-filgrastim	3	Anemia		Leukopenia
	Chronic heart failure				Peripheral neuropathy		Neutropenia
	Hypertension
	Dyslipidemia
	Asbestosis
	Chronic kidney disease
8	Hypertension	Age ≥70 years	2-on/2-off schedule with peg-filgrastim	3	Anemia
8	COPD	Age ≥70 years	2-on/2-off schedule with peg-filgrastim	3	Anemia

Abbreviations are DCM: Dilated cardiomyopathy, COPD: Chronic obstructive pulmonary disease.

Several patients required dose modifications or schedule adjustments during treatment, mainly because of hematological toxicity. Nevertheless, no patient permanently discontinued the eribulin treatment because of adverse events, and no treatment-related deaths were observed.

Safety and adverse events

The treatment-related adverse events are summarized in Table 2. Haematological toxicities, particularly neutropenia and leukopenia, were relatively common. These events were managed with dose adjustments, treatment delays, or supportive care, including the administration of granulocyte colony-stimulating factor, when appropriate.

The non-hematological toxicities included peripheral neuropathy and dysgeusia, which occurred in a subset of patients. These adverse events were generally mild to moderate in severity and were manageable with conservative measures. Importantly, no severe adverse cardiac events or clinically significant deterioration in cardiac function were observed during eribulin therapy.

Oncological outcomes and subsequent treatment

The oncological outcomes and treatments administered after eribulin therapy are shown in Table 3. During the follow-up period, six patients remained continuously disease-free (CDF), whereas two died of the disease (DOD).

Table 3.

Eribulin treatment outcomes, subsequent treatment, and oncological outcomes.

No.	Time to metastasis	Time to local recurrence	Subsequent treatment after eribulin	Duration of follow-up (months)	Oncological outcome
1	None	5 months	Two resection	23	DOD
2	67 months	None	None	73	DOD
3	None	None	None	20	CDF
4	None	None	None	23	CDF
5	None	None	None	34	CDF
6	None	None	None	16	CDF
7	None	None	None	26	CDF
8	None	None	None	19	CDF

Abbreviations are DOD: Died of disease, CDF: Continuous disease free.

The clinical courses of the two patients who experienced oncological events are summarized below. One patient with dedifferentiated liposarcoma of the retroperitoneum developed local recurrence 5 months after completion of eribulin therapy. The patient underwent two subsequent surgical resections; however, the third recurrence was deemed unresectable. Doxorubicin was administered at a reduced dose (80%), but treatment was discontinued after a single cycle due to grade 3 diarrhea. The patient was subsequently managed with best supportive care; however, she died of disease 23 months after eribulin therapy. Another patient with myxoid liposarcoma of the thigh developed multiple pulmonary metastases 67 months after eribulin therapy and was subsequently managed with best supportive care. The patient died of disease 73 months after eribulin therapy.

Discussion

In this retrospective study of a series of eight patients, we evaluated the feasibility, safety, and clinical outcomes of postoperative adjuvant eribulin administration in patients with localized STS, with a focus on older adults and those with notable comorbidities.

Anthracycline-based chemotherapy, with or without ifosfamide, has been the most extensively studied perioperative regimen for localized high-risk STS. However, its clinical benefits remain inconsistent, and treatment-related toxicity is a major concern, particularly in older adults and those with comorbidities. Large, randomized trials and meta-analyses have demonstrated the modest benefits of adjuvant anthracycline-based chemotherapy, while reporting substantial hematological and non-hematological toxicities that limit its feasibility in routine clinical practice.^10,11

In the present series, although hematological toxicities such as neutropenia and leukopenia were relatively common, they were manageable with dose modification and supportive care. Importantly, no severe cardiac adverse events were observed, despite the inclusion of older adults and patients with pre-existing cardiovascular disease in this case series. Given that cardiotoxicity is a major limitation of anthracycline use in the perioperative setting, these findings suggest that eribulin may represent a safer alternative in selected patients.

Gemcitabine-based regimens, such as gemcitabine plus docetaxel, have also been explored as alternative perioperative treatments; however, their roles remain limited and their toxicity profiles vary across studies.¹² Although no direct comparisons can be made in this small retrospective series, the safety and feasibility observed in our cohort appear to be comparable to those reported for established perioperative chemotherapy regimens.

The clinical significance of our findings lies in demonstrating that postoperative adjuvant eribulin can be administered safely to patients who are considered poor candidates for anthracycline-based chemotherapy. Older adult patients and those with significant comorbidities are frequently encountered in clinical practice; however, evidence guiding perioperative systemic treatment in this population remains limited. Our results suggest that eribulin may serve as a feasible therapeutic option in this underrepresented group.

This interpretation is supported by previous clinical reports demonstrating that eribulin can be administered with manageable toxicity and a low incidence of clinically significant cardiac adverse events, even in patients with contraindications to doxorubicin.^13,14 Furthermore, recent studies have explored its potential role beyond advanced disease. For example, a retrospective analysis demonstrated the feasibility of postoperative adjuvant eribulin administration in selected high-risk patients with liposarcoma who were not candidates for intensive chemotherapy.¹⁵ In addition, preclinical studies have shown that eribulin exhibits antiproliferative activity comparable to that of anthracycline-based treatment in undifferentiated pleomorphic sarcoma models, providing a biological rationale for its potential use beyond liposarcoma.¹⁶

Although eribulin has primarily been investigated in patients with advanced or metastatic liposarcoma and leiomyosarcoma, its clinical use varies by region. In the United States and Europe, its approval is limited to specific histological subtypes, whereas in Japan it is approved for soft tissue sarcoma regardless of histology and is used more broadly in routine practice. Therefore, the present study, which included multiple histological subtypes, reflects real-world clinical decision-making in Japan.

Furthermore, our previous real-world study of patients with advanced or metastatic STS demonstrated the favorable safety profile of eribulin, including in older adults and those with cardiovascular comorbidities.¹⁷ Although that study focused on advanced disease, the present analysis extends these observations to the postoperative adjuvant setting, supporting the feasibility of eribulin use across different clinical contexts.

This study has several limitations. First, it was a retrospective case series conducted at a single institution with a small sample size. Therefore, the findings should be interpreted with caution, and no definitive conclusions regarding efficacy can be drawn. Second, the absence of a control group precludes direct comparison with other perioperative chemotherapy regimens, and selection bias is inherent, as eribulin was preferentially administered to patients considered unsuitable for anthracycline-based chemotherapy. Third, oncological outcomes were assessed descriptively without formal statistical analysis, and no sample size calculation was performed. Despite these limitations, this study provides clinically relevant real-world data on the feasibility and safety of postoperative adjuvant eribulin administration in a high-risk population that is often underrepresented in prospective trials.

Conclusion

Eribulin was feasible and well-tolerated as postoperative adjuvant chemotherapy in older adult patients and those with severe comorbidities with localized STS. Although the current case series was not designed to evaluate efficacy, the absence of severe treatment-related complications, including clinically significant adverse cardiac events, supports the potential role of eribulin as a therapeutic option for patients considered poor candidates for anthracycline-based perioperative chemotherapy. These findings, along with previous real-world safety data, suggest that eribulin may be a useful component in multimodal treatment strategies for carefully selected high-risk patients. Further studies with larger cohorts are warranted to clarify its role in the perioperative management of STS.

Supplemental material

Supplemental material - Postoperative adjuvant eribulin in high-risk patients with soft tissue sarcoma: A retrospective study of eight cases

Supplemental material for Postoperative adjuvant eribulin in high-risk patients with soft tissue sarcoma: A retrospective study of eight cases by Yudai Murayama, Hirokazu Ideta, Rumi Nakagawa, Yasutaka Sukawa, Masanobu Takahashi, Hiroyuki Kawashima, Kazutaka Kikuta in Rare Tumors

Footnotes

Acknowledgements

We would like to thank Editage () for English language editing.

ORCID iD

Yudai Murayama

Ethical considerations

This study was conducted in accordance with the Declaration of Helsinki (as revised in 2024). According to the institutional policy of Tochigi Cancer Center, retrospective studies using fully anonymized clinical data are covered by the institutional comprehensive consent system and do not require individual Institutional Review Board approval. All patient data were fully de-identified prior to analysis.

Consent to participate

Informed consent for participation was waived due to the retrospective nature of the study and the use of anonymized data under the institutional comprehensive consent policy.

Consent for publication

Patient consent for publication was obtained as part of the institutional comprehensive consent process.

Author contributions

YM and KK contributed to the conception and design of the study. YM, HI, and RN collected the clinical data. YM analyzed and interpreted the data. YM drafted the manuscript. YS, MT, HK, and KK critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets presented in this study are available upon request from the corresponding author.*

Supplemental material

Supplemental material for this article is available online.

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