Bella Kaufman1, Ronnie Shapira‐Frommer1, Arcangela De Nicolo1, M. William Audeh1, Michael Friedlander1, Judith Balmañà1, Gillian Mitchell1, Georgeta Fried1, Salomon M. Stemmer1, Ayala Hubert1, Ora Rosengarten1, Mariana Steiner1, Niklas Dahl1, Karin Bowen1, Anitra Fielding2,1, Susan M. Domchek3,4,1
1Bella Kaufman and Ronnie Shapira-Frommer, Sheba Medical Center, Tel Hashomer; Georgeta Fried, Institute of Oncology, Rambam Health Care Campus; Mariana Steiner, Linn Medical Centre, Haifa; Salomon M. Stemmer, Rabin Medical Center, Petah Tikva; Ayala Hubert, Hadassah-Hebrew University Hospital, Sharett Institute of Oncology; Ora Rosengarten, Shaare Zedek Medical Centre, Jerusalem, Israel; Rita K. Schmutzler, Center for Familial Breast and Ovarian Cancer and Center of Integrated Oncology, Cologne, Germany;...
2AstraZeneca, Maccles-field, United Kingdom
3Abramson Cancer Center, University of Pennsylvania, 3400 Civic Center Blvd, 3 West Pavilion, Philadel-phia, PA 19104;
4Basser Research Center and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Tóm tắt
Purpose Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) –associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. Patients and Methods This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. Results A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease ≥ 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade ≥ 3 AEs were reported for 54% of patients; anemia was the most common (17%). Conclusion Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations. Olaparib warrants further investigation in confirmatory studies.
