Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer

// Saeed Rafii 1 , Charlie Gourley 2 , Rajiv Kumar 1 , Elena Geuna 1 , Joo Ern Ang 1 , Tzyvia Rye 2 , Lee-May Chen 3 , Ronnie Shapira-Frommer 4 , Michael Friedlander 5 , Ursula Matulonis 6 , Jacques De Greve 7 , Amit M. Oza 8 , Susana Banerjee 9 , L. Rhoda Molife 1 , Martin E. Gore 9 , Stan B. Kaye 1 and Timothy A. Yap 1 1 Drug Development Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK 2 University of Edinburgh Cancer Research UK Centre, Edinburgh, UK 3 University of California San Francisco, San Francisco, CA, USA 4 Sheba Medical Centre, Ramat Gan, Israel 5 Prince of Wales Cancer Centre, Randwick, Australia 6 Dana-Farber Cancer Institute, Boston, MA, USA 7 Oncologisch Centrum UZ Brussel, Brussels, Belgium 8 Princess Margaret Cancer Centre, University Health Network, Toronto, Canada 9 Gynae-Oncology Unit, Royal Marsden Hospital, London, UK Correspondence to: Timothy A. Yap, email: tyap@mdanderson.org Keywords: PARP inhibitor, olaparib, BRCA, ovarian cancer, predictive biomarkers Received: October 25, 2016 Accepted: February 22, 2017 Published: April 10, 2017 ABSTRACT 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