Induction therapy with paclitaxel and bevacizumab followed by switch maintenance therapy with eribulin in Japanese patients with HER2-negative metastatic breast cancer: a multicenter, collaborative, open-label, phase II clinical study for the SBCCSG 35 investigators

Abstract

BackgroundTo examine the efficacy and safety of induction therapy with paclitaxel and bevacizumab followed by switch maintenance therapy with eribulin (ISMT) in Japanese patients with HER2-negative metastatic breast cancer (MBC).MethodsPatients, who had previously undergone a maximum of 2 regimens of chemotherapy, received 3 cycles of induction therapy with paclitaxel (90 mg/m2 intravenously on days 1, 8, and 15 followed by 1-week drug holiday) and bevacizumab (10 mg/kg intravenously after the completion of paclitaxel administration on days 1 and 15). Patients who had complete response, partial response, or stable disease underwent switch maintenance therapy with eribulin (1.4 mg/m2 intravenously on days 1 and 8 followed by 1-week drug holiday). The primary endpoint was time to treatment failure (TTF) for ISMT.ResultsFifty-one eligible patients (median age: 66 years; range: 35–74) were enrolled: 19 (37.3%) and 32 (62.7%) had stage IV and recurrence, respectively, 42 (82.4%) had visceral metastases, and 45 (88.2%) received eribulin—38 of whom showed disease progression, and 40 (78.4%) underwent post therapy. Median TTF was 9.2 months (95% confidence interval [CI]: 7.3–11.1), median progression-free survival was 10.7 months (95% CI: 9.6–11.8), and median overall survival was 20.0 months (95% CI: 16.0–24.0). Relative dose intensity was 97.7% (range: 33.3–100.0) for induction therapy and was 83.3% (range: 49.3–100.6%) for eribulin maintenance therapy. The most common adverse event was alopecia (51 [100%]) in induction therapy and was peripheral sensory neuropathy (37 [82.2%]) in eribulin maintenance therapy. Eribulin was effective with manageable tolerability.ConclusionsISMT may be a promising therapeutic option for patients with MBC.Trial registrationUMIN000015971. Registration date: January 1, 2015.

Effectiveness and safety of eribulin in Japanese patients with HER2-negative, advanced breast cancer: a 2-year post-marketing observational study in a real-world setting

“…These included studies on eribulin as a first-or second-line treatment, although direct comparisons are limited by study design differences (e.g. the majority of the studies assessed eribulin safety by adverse events) [9,10,15,16,18,19]. Hence, eribulin was well-tolerated, as shown in previous studies, although ADRs, such as the hematologic events, should be taken into consideration for eribulin administration, regardless of the patients' eribulin treatment line status.…”

“…The efficacy and safety of eribulin as the first-or secondline treatment was not explored in randomized controlled trials. However, some clinical trials (mainly phase 2) and a realworld study reported the efficacy and safety of eribulin as a first-or second-line treatment [6][7][8][9][10][11][12][13][14][15]. Jacot et al reported the activities of eribulin among metastatic breast cancer patients in a multicenter national observational Epidemiological Strategy and Medical Economic (ESME) program in a realworld setting [14].…”

First-line bevacizumab and eribulin combination therapy for HER2-negative metastatic breast cancer: Efficacy and safety in the GINECO phase II ESMERALDA study

“…Interestingly, a switch maintenance approach, similar to that evaluated in IMELDA, was explored by Japanese investigators. Patients received single-agent eribulin after initial bevacizumab/paclitaxel combination therapy [ 33 ]. Although this approach showed activity (median PFS of 10.7 months), neuropathy was the most common adverse event during eribulin maintenance therapy, somewhat undermining the rationale for switching from paclitaxel to eribulin.…”

Capecitabine in Combination with Endocrine Therapy as Maintenance Therapy after Bevacizumab Plus Paclitaxel Induction Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: KBCSG-TR1214

“…Moreover, the Dutch Breast Cancer Research Group compared intermittent versus continuous first-line treatment with bevacizumab plus paclitaxel; unfortunately, this strategy was not successful to demonstrate the noninferiority of the intermittent regimen to continuous treatment in terms of PFS or OS [22]. Promising results have also been reported in a Japanese phase 2 trial in which patients underwent induction therapy with bevacizumab plus paclitaxel followed by maintenance therapy with eribulin (median PFS: 10.7 months; OS: 20.0 months) [23]. Therefore, previous studies examining maintenance therapy have not yielded consistent results, and thus there is a need to explore a maintenance therapy with an optimal balance of toxicity and efficacy.…”