A phase I/II trial of olaparib in combination with eribulin in patients with advanced or metastatic triple negative breast cancer (TNBC) previously treated with anthracyclines and taxanes: The analyses of efficacy and safety from phase II.
1080 Background: Metastatic TNBC has a poorer prognosis compared with other subtypes because of the lack of a confirmed effective target. Eribulin is a standard treatment for metastatic TNBC and olaparib (Lynparza), a PARP inhibitor, has shown efficacy in breast cancer with germline (g)BRCA1/2 mutations. We designed this Phase I/II trial with an expectation of a synergistic effect for metastatic TNBC patients (pts) enrolled, irrespective of gBRCA1/2 mutation status. In Phase I, we reported at ASCO 2015 the recommended dose of olaparib tablets was 300 mg BID. We will present the efficacy and safety of this combination treatment from phase II. Methods: Pts with advanced or metastatic TNBC previously treated with anthracyclines and taxanes were eligible. Confirmation of a BRCA1/2 mutation was not mandatory before enrollment. This trial was conducted at 8 institutions in Japan. According to the results from Phase I, 1.4 mg/m2 of eribulin was administered intravenously on Days 1 and 8. Olaparib tablets were orally administered at a dose of 300 mg BID. The primary efficacy endpoint was tumor response rate. Results: From June 2014 to December 2014, 24 pts were enrolled. The median age was 46 years old (range: 27 to 73). The median number of prior chemotherapy regimens was 3 (range: 2 to 6). Sixteen pts (66.7%) had visceral metastasis and 8 non visceral metastasis. The relative dose intensity of eribulin was 74.9% and olaparib 75.4%. The response rate was 37.5% (95% CI: 18.8–59.4), including CR in 1 pt. Median progression free survival was 4.2 months (95% CI: 2.7–7.6). The median overall survival was not reached and 11 pts died. Severe adverse events (G3 and G4) were leukocytopenia (83.3%), neutropenia (83.3%), febrile neutropenia (33.3%), anemia (37.5%) and thrombosis (8.3%). Conclusions: The combination of olaparib and eribulin indicates a promising clinical interaction in pts with metastatic TNBC, without intolerable adverse events. The next step is exploratory research into the relationship between gBRCA1/2 mutation status and/or HRD, and the clinical efficacy of this combination treatment. Clinical trial information: 12.