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Br J Cancer. 2015 Jul 28;113(3):396-402. doi: 10.1038/bjc.2015.256. Epub 2015 Jul 16.

Long-term safety and anti-tumour activity of olaparib monotherapy after combination with carboplatin and paclitaxel in patients with advanced breast, ovarian or fallopian tube cancer.

Author information

1
Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.
2
1] Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands [2] Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, Utrecht 3584 CG, The Netherlands.
3
Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.
4
1] Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands [2] Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, Utrecht 3584 CG, The Netherlands.

Abstract

BACKGROUND:

Olaparib (AZD2281), a PARP-1/2 inhibitor, has been extensively investigated in clinical trials. However, limited clinical data are available about its long-term safety and anti-tumour activity.

METHODS:

Patients had first participated in a phase I study of olaparib combined with carboplatin and/or paclitaxel. They continued with olaparib monotherapy in their best interest if they failed to tolerate the combination due to the treatment-related adverse events (TRAEs). Safety data were collected by physical examination and regular laboratory evaluations. Disease evaluations were performed by CT scan.

RESULTS:

At data cutoff, 21 patients were included; 10 with breast, 9 with ovarian and 2 with fallopian tube cancer of whom 16 patients had a BRCA mutation (13 BRCA1; 3 BRCA2). TRAEs were mostly haematological and most prominent shortly after switching from combination to monotherapy, probably due to carry-over effects of chemotherapy. Over time, both severity and frequency of TRAEs decreased. Responses to olaparib were durable with a median treatment duration of 52 (range 7-183) weeks. In total, nine (43%) patients were still on study at data cutoff.

CONCLUSION:

Continued long-term daily olaparib was found to be safe and tolerable. Encouragingly, patients who showed a favourable response on earlier combination therapy maintained this response on olaparib monotherapy.

PMID:
26180927
PMCID:
PMC4522644
DOI:
10.1038/bjc.2015.256
[Indexed for MEDLINE]
Free PMC Article

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