title: Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study.
abstract: BACKGROUND
  Olaparib (AZD2281) is a small-molecule, potent oral poly(ADP-ribose) polymerase (PARP) inhibitor. We aimed to assess the safety and tolerability of this drug in patients without BRCA1 or BRCA2 mutations with advanced triple-negative breast cancer or high-grade serous and/or undifferentiated ovarian cancer.
  
  
  METHODS
  In this phase 2, multicentre, open-label, non-randomised study, women with advanced high-grade serous and/or undifferentiated ovarian carcinoma or triple-negative breast cancer were enrolled and received olaparib 400 mg twice a day. Patients were stratified according to whether they had a BRCA1 or BRCA2 mutation or not. The primary endpoint was objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST). All patients who received treatment were included in the analysis of toxic effects, and patients who had measurable lesions at baseline were included in the primary efficacy analysis. This trial is registered at ClinicalTrials.gov, number NCT00679783.
  
  
  RESULTS
  91 patients were enrolled (65 with ovarian cancer and 26 breast cancer) and 90 were treated between July 8, 2008, and Sept 24, 2009. In the ovarian cancer cohorts, 64 patients received treatment. 63 patients had target lesions and therefore were evaluable for objective response as per RECIST. In these patients, confirmed objective responses were seen in seven (41%; 95% CI 22-64) of 17 patients with BRCA1 or BRCA2 mutations and 11 (24%; 14-38) of 46 without mutations. No confirmed objective responses were reported in patients with breast cancer. The most common adverse events were fatigue (45 [70%] of patients with ovarian cancer, 13 [50%] of patients with breast cancer), nausea (42 [66%] and 16 [62%]), vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven [27%]).
  
  
  CONCLUSIONS
  Our study suggests that olaparib is a promising treatment for women with ovarian cancer and further assessment of the drug in clinical trials is needed.
  
  
  BACKGROUND
  AstraZeneca.
authors.affiliation: BC Cancer Agency, Vancouver, Canada. kgelmon@bccancer.bc.ca
authors.forename: Karen A
authors.initials: KA
authors.lastname: Gelmon
authors.forename: Marc
authors.initials: M
authors.lastname: Tischkowitz
authors.forename: Helen
authors.initials: H
authors.lastname: Mackay
authors.forename: Kenneth
authors.initials: K
authors.lastname: Swenerton
authors.forename: André
authors.initials: A
authors.lastname: Robidoux
authors.forename: Katia
authors.initials: K
authors.lastname: Tonkin
authors.forename: Hal
authors.initials: H
authors.lastname: Hirte
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
authors.forename: Blake
authors.initials: B
authors.lastname: Gilks
authors.forename: Rinat
authors.initials: R
authors.lastname: Yerushalmi
authors.forename: Euan
authors.initials: E
authors.lastname: Macpherson
authors.forename: James
authors.initials: J
authors.lastname: Carmichael
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002170:Canada; D002277:Carcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000556:secondary; D002454:Cell Differentiation; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D010793:Phthalazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C551750:BRCA2 protein, human; C508053:ERBB2 protein, human; C531550:olaparib