Phase II, multicentre, randomised trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy in patients with HER2-negative metastatic breast cancer

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Paclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel.</P> <P><B>Patients and methods</B></P> <P>This study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC. We hypothesised that EG chemotherapy would not be inferior to PG chemotherapy. The primary end-point was progression-free survival (PFS), which was estimated to be 70% at 6 months for each arm. The secondary end-points were as follows: OS, neuropathic scale, toxicity and clinical benefit rate.</P> <P><B>Results</B></P> <P>A total of 118 patients (median age: 50, 24–66) were enrolled between March 2015 and March 2016 and were randomly assigned to PG (<I>n</I> = <I>59</I>) or EG (<I>n</I> = <I>59</I>) chemotherapy. The mean number of metastatic sites was 3 (range 1–8). The 6-month PFS rates for both arms were 72% for EG and 73% for PG (<I>P</I> = <I>0.457</I>). There was no significant difference in OS between the two groups (not reached versus 21.2 months, <I>P</I> = <I>0.2234</I>). The median number of chemotherapy cycles for both groups was 10 for EG and 8 for PG (range 2–32). Clinical benefit rates were 44% for EG and 49% for PG. Major toxicities were neutropenia and neurotoxicity. Grade II or above neurotoxicity was more common with PG than with EG (13.6% for EG versus 45.8% for PG, <I>P</I> < <I>0.0001</I>).</P> <P><B>Conclusion</B></P> <P>EG chemotherapy had similar clinical benefits to PG chemotherapy in terms of PFS but less neurotoxicity.</P> <P><B>Trial registration</B></P> <P>KCSG BR13-11; ClinicalTrials.gov, NCT02263495.</P> <P><B>Highlights</B></P> <P> <UL> <LI> This study was a prospective randomized phase II, multicentre study comparing EG with PG for MBC patients. </LI> <LI> The 6-month PFS rates for both arms were 72% for EG and 73% for PG (<I>P</I> = 0.457). </LI> <LI> EG chemotherapy had similar clinical benefits to PG chemotherapy in terms of progression-free survival but less neurotoxicity. </LI> </UL> </P>