• Saeed Rafii, Charlie Gourley, Rajiv Kumar, Elena Geuna, Ern Ang Joo J Drug Development Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK., Tzyvia Rye, Lee-May Chen, Ronnie Shapira-Frommer, Michael Friedlander, Ursula Matulonis, Jacques De Greve, Amit M Oza, Susana Banerjee, L Rhoda Molife, Martin E Gore, Stan B Kaye, and Timothy A Yap.
• Drug Development Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
• Oncotarget. 2017 Jul 18; 8 (29): 47154-47160.

BackgroundThe 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.Results108 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.MethodsWe 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.ConclusionPTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

40 keywords...

hide…