Phase II trial of eribulin in patients who do not achieve pathologic complete response (pCR) following neoadjuvant chemotherapy

Yardley, Denise A.; Peacock, N. W.; Daniel, Brooke R.; Anz, Betrand; Molthrop, David; Shroff, Sonalee K.; Young, Robyn R.; Jankov, Aleksander; Woude, Amy Vander; Shastry, Mythili; Pasek, Johanna; DeBusk, Laura M.; Hainsworth, John D.

doi:10.1007/s10549-020-05563-z

Cited by 6 publications

(5 citation statements)

References 31 publications

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“…The neoadjuvant HOPE trial 14 failed to demonstrate high eribulin efficacy, as measured by pCR, in patients with TNBC treated with anthracycline and taxane. Moreover , Yardley et al studied the role of additional eribulin as post-neoadjuvant in a phase II trial in breast cancer patients with residual invasive disease after taxane and/or anthracycline-based neoadjuvant therapy 15 . The disease-free survival results suggested a lack of benefit of adjuvant eribulin and did not reach the targeted endpoints of the study in any breast cancer subtype.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial

Pascual¹,

Oliveira

Villagrasa³

et al. 2021

npj Breast Cancer

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Eribulin prolongs overall survival in patients with pre-treated advanced breast cancer. However, no biomarker exists to prospectively select patients who will benefit the most from this drug. SOLTI-1007-NeoEribulin is a phase II, open-label, two-cohort, exploratory pharmacogenomic study in patients with clinical stage I–II HER2-negative breast cancer receiving neoadjuvant eribulin monotherapy treatment. Primary objective was to explore the association of baseline tumor gene expression with pathological complete response in the breast (pCRB) at surgery. Key secondary objectives were pCRB rates in all patients and according to HR status, gene expression changes during treatment and safety. One-hundred one hormonal receptor-positive (HR + ) and seventy-three triple-negative breast cancer (TNBC) patients were recruited. The pCRB rates were 6.4% in all patients, 4.9% in HR + disease and 8.2% in TNBC. The TNBC cohort was interrupted due to a progression disease rate of 30.1%. The pCRB rates differed according to intrinsic subtypes: 28.6% in HER2-enriched, 11.1% in Normal-like, 7.9% in Luminal B, 5.9% in Basal-like and 0% in Luminal A (HER2-enriched vs. others odds ratio = 7.05, 95% CI 1.80–42.14; p-value = 0.032). Intrinsic subtype changes at surgery occurred in 33.3% of cases, mostly (49.0%) Luminal B converting to Luminal A or Basal-like converting to Normal-like. Baseline tumor-infiltrating lymphocytes (TILs) were significantly associated with pCR. Eribulin showed a good safety profile with a low response and pCRB rates. Patients with HER2-negative disease with a HER2-enriched profile may benefit the most from eribulin. In addition, significant biological activity of eribulin is observed in Luminal B and Basal-like subtypes.

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Section: Discussionmentioning

confidence: 99%

Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial

Pascual¹,

Oliveira

Villagrasa³

et al. 2021

npj Breast Cancer

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“…However, in the adjuvant setting after tumor resection, a residual small tumor burden may allow activation of vascular remodeling by eribulin. A phase II trial of postoperative eribulin in breast cancer patients who did not achieve pCR following standard neoadjuvant chemotherapy showed that it was feasible and well tolerated (20). However, that study did not achieve its targeted 2-year DFS endpoints (improvements of 40%, 15%, and 25% in TNBC, ER+, and HER2+, respectively) in any of the three cohorts treated, and the 2-year DFS in each cohort was similar to the result in the control arms of several large studies in which patients not achieving pCR received no subsequent adjuvant treatment.…”

Section: Discussionmentioning

confidence: 99%

A Phase II Study of Sequential Treatment With Anthracycline and Taxane Followed By Eribulin in Patients With HER2-Negative, Locally Advanced Breast Cancer (JBCRG-17)

Fukada

Ito

Kondo

et al. 2021

Preprint

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PurposeThe sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy (NAC) has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC.MethodsIn this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative.ResultsA preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease (cPD) rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade >3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%)ConclusionSequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.

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“…However, in the adjuvant setting after tumor resection, a residual small tumor burden may allow activation of vascular remodeling by eribulin. A phase II trial of postoperative eribulin in breast cancer patients who did not achieve pCR following standard neoadjuvant chemotherapy showed that it was feasible and well tolerated [ 25 ]. However, that study did not achieve its targeted 2-year DFS endpoints (improvements of 40%, 15%, and 25% in TNBC, ER+, and HER2+, respectively) in any of the three cohorts treated, and the 2-year DFS in each cohort was similar to the result in the control arms of several large studies in which patients not achieving pCR received no subsequent adjuvant treatment.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of sequential treatment with anthracycline and taxane followed by eribulin in patients with HER2-negative, locally advanced breast cancer (JBCRG-17)

Fukada

Ito

Kondo

et al. 2021

Breast Cancer Res Treat

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Purpose The sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC. Methods In this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2–3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative. Results A preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade ≥ 3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%). Conclusion Sequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.

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Phase II trial of eribulin in patients who do not achieve pathologic complete response (pCR) following neoadjuvant chemotherapy

Cited by 6 publications

References 31 publications

Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial

Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial

A Phase II Study of Sequential Treatment With Anthracycline and Taxane Followed By Eribulin in Patients With HER2-Negative, Locally Advanced Breast Cancer (JBCRG-17)

A phase II study of sequential treatment with anthracycline and taxane followed by eribulin in patients with HER2-negative, locally advanced breast cancer (JBCRG-17)

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