Back to Search
Start Over
A phase I/II trial of olaparib tablet in combination with eribulin in Japanese patients with advanced or metastatic triple-negative breast cancer previously treated with anthracyclines and taxanes
- Source :
- European Journal of Cancer. 109:84-91
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Background We conducted a multicenter phase I/II trial of olaparib plus eribulin in Japanese patients with advanced or metastatic triple-negative breast cancer (TNBC) to determine the recommended phase II dose (RP2D) (phase I) and to examine the efficacy and safety (phase II) (UMIN00009498) of the combined therapy. Patients and methods In phase I, olaparib tablet was orally administered twice daily from level 1:25 mg BID to level 7:300 mg BID, with 1.4 mg/m2 of eribulin on days 1 and 8. In phase II, patients were treated with RP2D to assess the response rate (independent review). The planned sample size was 24 with a threshold of 10%. Results One of the 24 patients enrolled in phase I experienced dose-limiting toxicity. The RP2D was established as 300 mg twice daily for olaparib and 1.4 mg/m2 for eribulin. Among the 24 patients in phase II, the median number of administered courses was 5.5 (range: 1–28). Grade ≥III adverse events included neutropenia (83.3%), leucopenia (83.3%), anaemia (41.7%), febrile neutropenia (33.3%) and thrombosis (8.3%). The response rate was 29.2% (independent; N = 7/24; 90% confidence interval [CI]; 14.6–47.9). Median progression-free survival and overall survival were 4.2 (95% CI, 3.0–7.4) and 14.5 (95% CI, 4.8–22.0) months, respectively. Germline BRCA1/2 mutation status was observed in three patients in phase I and 2 patients in phase II, respectively. The Cmax and area under the curve for olaparib increased in a dose-dependent manner, and these parameters for eribulin and olaparib were not influenced by each other. Conclusions Combination therapy of olaparib with eribulin shows antitumour activity against advanced or metastatic TNBC, but caution must be exercised in the presence of febrile neutropenia.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
Triple Negative Breast Neoplasms
Piperazines
chemistry.chemical_compound
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Anthracyclines
Tissue Distribution
Aged, 80 and over
Area under the curve
Ketones
Middle Aged
Prognosis
Survival Rate
Area Under Curve
Lymphatic Metastasis
030220 oncology & carcinogenesis
PARP inhibitor
Female
Taxoids
Tablets
Eribulin
Adult
medicine.medical_specialty
Adolescent
Maximum Tolerated Dose
Combination therapy
Neutropenia
Olaparib
Young Adult
03 medical and health sciences
Breast cancer
Internal medicine
medicine
Humans
Furans
Aged
Salvage Therapy
business.industry
medicine.disease
030104 developmental biology
chemistry
Drug Resistance, Neoplasm
Phthalazines
business
Febrile neutropenia
Follow-Up Studies
Subjects
Details
- ISSN :
- 09598049
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer
- Accession number :
- edsair.doi.dedup.....cd2caf9b90cffb6964f1518efe3eccd0