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Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer.

ABSTRACT: Residual disease (RD) after neoadjuvant chemotherapy carries an increased risk for recurrence. Ixabepilone has activity in anthracycline/taxanes-resistant breast cancer. We explored adjuvant ixabepilone in patients with significant RD HER2-negative breast cancer.A phase II study in patients with residual cancer burden II or III randomized to ixabepilone versus observation was conducted. Circulating tumor cells (CTCs) were measured at baseline and at 9 and 18 weeks. Survival probabilities were estimated by Kaplan-Meier product limit. Toxicities were reported as proportions in the ixabepilone arm.Accrual was stopped because of ixabepilone toxicity. Sixty-seven patients were registered; 43 were randomized, 19 received ixabepilone, and 24 went to observation. One patient (9.1%) in the observation arm versus 2 patients (18.2%) in the ixabepilone arm had CTCs at 18 weeks (P = 1.0). Three-year recurrence-free survival and overall survival were 94% and 82%, and 100% and 79% in the observation and ixabepilone arms (P = .35 and .18), respectively. Most common adverse events (AEs) included fatigue, pain, neuropathy, constipation, nausea, rash, anorexia, and diarrhea. Serious AEs included pain (63.2%), fatigue (31.6%), and neuropathy (31.6%).Adjuvant ixabepilone in patients with significant RD after neoadjuvant chemotherapy was difficult to administer because of AEs and did not change the presence of CTC or affect survival outcomes. NCT00877500.

SUBMITTER: Gonzalez-Angulo AM

PROVIDER: S-EPMC4568133 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer.

Gonzalez-Angulo Ana M AM Lei Xiudong X Alvarez Richardo H RH Green Majorie C MC Murray James L JL Valero Vicente V Koenig Kimberly B KB Ibrahim Nuhad K NK Litton Jennifer K JK Nair Lakshmy L Krishnamurthy Savitri S Hortobagyi Gabriel N GN Meric-Bernstam Funda F

Clinical breast cancer 20150324 5

<h4>Background</h4>Residual disease (RD) after neoadjuvant chemotherapy carries an increased risk for recurrence. Ixabepilone has activity in anthracycline/taxanes-resistant breast cancer. We explored adjuvant ixabepilone in patients with significant RD HER2-negative breast cancer.<h4>Methods</h4>A phase II study in patients with residual cancer burden II or III randomized to ixabepilone versus observation was conducted. Circulating tumor cells (CTCs) were measured at baseline and at 9 and 18 we ...[more]

PMID: 25913905

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Project description:Lessons learnedThe combination of eribulin with 5-fluorouracil, either doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) was not superior to the combination of paclitaxel with FAC/FEC and was associated with greater hematologic toxicity. Eribulin followed by an anthracycline-based regimen is not recommended as a standard neoadjuvant therapy in nonmetastatic operable breast cancer.BackgroundNeoadjuvant systemic therapy is the standard of care for locally advanced operable breast cancer. We hypothesized eribulin may improve the pathological complete response (pCR) rate compared with paclitaxel.MethodsWe conducted a 1:1 randomized open-label phase II study comparing eribulin versus paclitaxel followed by 5-fluorouracil, either doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) in patients with operable HER2-negative breast cancer. pCR and toxicity of paclitaxel 80 mg/m2 weekly for 12 doses or eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle for 4 cycles followed by FAC/FEC were compared.ResultsAt the interim futility analysis, in March 2015, 51 patients (28 paclitaxel, 23 eribulin) had received at least one dose of the study drug and were thus evaluable for toxicity; of these, 47 (26 paclitaxel, 21 eribulin) had undergone surgery and were thus evaluable for efficacy. Seven of 26 (27%) in the paclitaxel group and 1 of 21 (5%) in the eribulin group achieved a pCR, and this result crossed a futility stopping boundary. In the paclitaxel group, the most common serious adverse events (SAEs) were neutropenic fever (grade 3, 3 patients, 11%). In the eribulin group, nine patients (39%) had neutropenia-related SAEs, and one died of neutropenic sepsis. The study was thus discontinued. For the paclitaxel and eribulin groups, the 5-year event-free survival (EFS) rates were 81.8% and 74.0% (hazard ratio [HR], 1.549; 95% confidence interval [CI], 0.817-2.938; p = .3767), and the 5-year overall survival (OS) rates were 100% and 84.4% (HR, 5.813; 95% CI, 0.647-52.208; p = .0752), respectively.ConclusionWe did not observe a higher proportion of patients undergoing breast conservation surgery in the eribulin group than in the paclitaxel group. The patients treated with eribulin were more likely to undergo mastectomy and less likely to undergo breast conservation surgery, but the difference was not statistically significant. As neoadjuvant therapy for operable HER2-negative breast cancer, eribulin followed by FAC/FEC is not superior to paclitaxel followed by FAC/FEC and is associated with a higher incidence of neutropenia-related serious adverse events.

Project description:Purpose The combination of taxanes and anthracyclines is still the mainstay of chemotherapy for early breast cancer. Capecitabine is an active drug with a favorable toxicity profile, showing strong anti-tumor activity against metastatic breast cancer. This trial assessed the efficacy and safety of the TX regimen (docetaxel and capecitabine) and compared it with the TE (docetaxel and epirubicin) regimen in locally advanced or high risk early HER2-negative breast cancer. Patients and methods This randomized clinical trial was conducted at five academic centers in China. Eligible female patients were randomly assigned (1:1) to the TX (docetaxel 75 mg/m2 d1 plus capecitabine 1000 mg/m2 twice d1–14, q3w) or TE (docetaxel 75 mg/m2 d1 plus epirubicin 75 mg/m2 d1, q3w) groups for four cycles. The primary endpoint was a pathological complete response in the breast (pCR). Secondary endpoints included pCR in the breast and axilla, invasive disease-free survival (iDFS), overall survival (OS), and safety. Results Between September 1, 2012, and December 31, 2018, 113 HER2-negative patients were randomly assigned to the study groups (TX: n = 54; TE: n = 59). In the primary endpoint analysis, 14 patients in the TX group achieved a pCR, and nine patients in the TE group achieved a pCR (25.9% vs. 15.3%), with a not significant difference of 10.6% (95% CI -6.0–27.3%; P = 0.241). In a subgroup with high Ki-67 score, TX increased the pCR rate by 24.2% (95% CI 2.2–46.1%; P = 0.029). At the end of the 69-month median follow-up period, both groups had equivalent iDFS and OS rates. TX was associated with a higher incidence of hand-foot syndrome and less alopecia, with a manageable toxicity profile. Conclusion The anthracycline-free TX regimen yielded comparable pCR and long-term survival rates to the TE regimen. Thus, this anthracycline-free regimen could be considered in selected patients. Trial Registration ACTRN12613000206729 on 21/02/2013, retrospectively registered. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-10439-0.

Project description:BackgroundNeoadjuvant anthracycline-taxane-based chemotherapy (ChT) is a standard of care treatment option for stage II-III breast cancer (BC) patients. However, the optimal duration of neoadjuvant ChT has been poorly investigated so far.Material and methodsWe retrospectively retrieved clinical data of patients with stage II-III human epidermal growth factor receptor 2-negative (HER2-) BC who were treated between October 2007 and January 2018 with neoadjuvant AT (doxorubicin-paclitaxel) for three cycles followed by CMF (cyclophosphamide-methotrexate-5-fluorouracil) for three cycles (cohort A) or with four AT cycles followed by four CMF cycles (cohort B). The aim of our study was to investigate the impact of neoadjuvant ChT duration (cohort A versus cohort B) on pathological complete response (pCR) rates, disease-free survival (DFS) and overall survival (OS).ResultsOf 209 HER2- BC patients included, 62 had triple-negative breast cancer (TNBC) and 147 had hormone receptor-positive (HR+) BC. Median age was 48 years (range 30-74 years). A total of 111 patients belonged to cohort A and 98 patients belonged to cohort B. pCR was detected in 29 (13.9%) patients, 25 (40.3%) of whom had TNBC and four (2.7%) had HR+ HER2- BC. Patients achieving pCR had significantly longer DFS and OS, with statistical significance reached only in patients with TNBC. We found no differences between cohort A and cohort B in terms of pCR rates (15.3% versus 12.2%; p = 0.55), DFS (p = 0.49) or OS (p = 0.94). The incidence of grade 3/4 adverse events was similar in cohort A versus cohort B as well (22.5% versus 19.4%; p = 0.54).ConclusionShorter duration of neoadjuvant anthracycline-taxane ChT was not associated with worse clinical outcomes in patients with stage II-III BC. Prospective studies are needed to evaluate whether the duration of neoadjuvant anthracycline-taxane-based ChT can be reduced in specific patient subgroups without negatively affecting clinical outcomes.

Dataset Information

Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer.

Publications

Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer.

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