First report of eribulin in combination with pertuzumab and trastuzumab for advanced HER2-positive breast cancer

Kazuhiro Araki, Ippei Fukada, Hiroyo Yanagi, Kokoro Kobayashi, Tomoko Shibayama, Rie Horii, Shunji Takahashi, Futoshi Akiyama, Shinji Ohno, Yoshinori Ito

The efficacy and safety of continuing multiple anti-HER2 therapies in advanced breast cancer (ABC) patients remains unclear. This study investigated eribulin in combination with pertuzumab and trastuzumab for both taxane- and trastuzumab-pretreated HER2-positive ABC patients. In a single-institute, single-arm, open-label, phase II trial, HER2-positive ABC patients who had previously received taxanes and trastuzumab were treated with eribulin in combination with pertuzumab and trastuzumab. The pharmacokinetics of eribulin in this combination were assessed in 6 patients. Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 12 weeks thereafter. The primary endpoint was objective response rate (ORR). A total of 30 patients (median age, 58 years; range, 31-76) were enrolled, with a median number of previous chemotherapy regimens of 3.5 (range: 1-9) in the metastatic setting. Pharmacokinetic parameters of eribulin in this combination were similar to previous reports of eribulin monotherapy. ORR was 34.8% (95% CI: 16.4-57.3, n = 23), and median progression-free survival was 42.6 weeks (95% CI: 20.3-51.9, n = 30). Clinical benefit rate was 60.9% (95% CI: 16.4-57.3). The most common grade 3/4 adverse event was neutropenia in 20 patients (66.7%). A dose reduction of eribulin was required in 27 patients due to adverse events, particularly grade 3 neutropenia. Eribulin in combination with pertuzumab and trastuzumab was well tolerated in heavily pretreated patients. Eribulin may be a viable treatment option when used in combination with pertuzumab and trastuzumab for HER2-positive ABC patients (UMIN Clinical Trial Registry identification number, UMIN000012375).