Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.
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Date
2017-07ICR Author
Author
Rafii, S
Gourley, C
Kumar, R
Geuna, E
Ern Ang, J
Rye, T
Chen, L-M
Shapira-Frommer, R
Friedlander, M
Matulonis, U
De Greve, J
Oza, AM
Banerjee, S
Molife, LR
Gore, ME
Kaye, SB
Yap, TA
Type
Journal Article
Metadata
Show full item recordAbstract
Background The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib.Results 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib.Methods We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib.Conclusion PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.
Collections
Subject
Humans
Ovarian Neoplasms
Neoplasm Metastasis
Recurrence
Piperazines
Phthalazines
BRCA1 Protein
BRCA2 Protein
Antineoplastic Agents
Neoplasm Staging
Prognosis
Treatment Outcome
Survival Analysis
Germ-Line Mutation
Adult
Aged
Middle Aged
Female
Neoplasm Grading
Poly(ADP-ribose) Polymerase Inhibitors
Research team
Medicine Drug Development Unit (de Bono)
Medicine Drug Development Unit (Kaye)
Language
eng
Date accepted
2017-02-22
License start date
2017-07
Citation
Oncotarget, 2017, 8 (29), pp. 47154 - 47160