Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer Journal Article
| Authors: | Kaye, S. B.; Lubinski, J.; Matulonis, U.; Ang, J. E.; Gourley, C.; Karlan, B. Y.; Amnon, A.; Bell-Mcguinn, K. M.; Chen, L. M.; Friedlander, M.; Safra, T.; Vergote, I.; Wickens, M.; Lowe, E. S.; Carmichael, J.; Kaufman, B. |
| Article Title: | Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer |
| Abstract: | Purpose: Olaparib (AZD2281), an orally active poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in BRCA1- or BRCA2-deficient cells, has shown promising clinical efficacy in nonrandomized phase II trials in patients with ovarian cancer with BRCA1 or BRCA2 deficiency. We assessed the comparative efficacy and safety of olaparib and pegylated liposomal doxorubicin (PLD) in this patient population. Patients and Methods: In this multicenter, open-label, randomized, phase II study, patients with ovarian cancer that recurred within 12 months of prior platinum therapy and with confirmed germline BRCA1 or BRCA2 mutations were enrolled. Patients were assigned in a 1:1:1 ratio to olaparib 200 mg twice per day or 400 mg twice per day continuously or PLD 50 mg/m 2 intravenously every 28 days. The primary efficacy end point was Response Evaluation Criteria in Solid Tumors (RECIST) -assessed progression-free survival (PFS). Secondary end points included objective response rate (ORR) and safety. Results: Ninety-seven patients were randomly assigned. Median PFS was 6.5 months (95% CI, 5.5 to 10.1 months), 8.8 months (95% CI, 5.4 to 9.2 months), and 7.1 months (95% CI, 3.7 to 10.7 months) for the olaparib 200 mg, olaparib 400 mg, and PLD groups, respectively. There was no statistically significant difference in PFS (hazard ratio, 0.88; 95% CI, 0.51 to 1.56; P = .66) for combined olaparib doses versus PLD. RECIST-assessed ORRs were 25%, 31%, and 18% for olaparib 200 mg, olaparib 400 mg, and PLD, respectively; differences were not statistically significant. Tolerability of both treatments was as expected based on previous trials. Conclusion: The efficacy of olaparib was consistent with previous studies. However, the efficacy of PLD was greater than expected. Olaparib 400 mg twice per day is a suitable dose to explore in further studies in this patient population. © 2011 by American Society of Clinical Oncology. |
| Keywords: | adult; controlled study; treatment response; aged; aged, 80 and over; disease-free survival; middle aged; survival analysis; gene mutation; major clinical study; overall survival; mutation; constipation; drug tolerability; fatigue; cancer recurrence; doxorubicin; diarrhea; drug efficacy; drug safety; prospective studies; ovarian neoplasms; progression free survival; quality of life; ovary cancer; phase 2 clinical trial; anemia; tumor volume; nausea; randomized controlled trial; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; brca1 protein; brca2 protein; abdominal pain; asthenia; rash; genes, brca1; genes, brca2; multicenter study; urinary tract infection; piperazines; hand foot syndrome; polyethylene glycols; olaparib; phthalazines; palmar plantar erythrodysesthesia syndrome |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 30 |
| Issue: | 4 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2012-02-01 |
| Start Page: | 372 |
| End Page: | 379 |
| Language: | English |
| DOI: | 10.1200/jco.2011.36.9215 |
| PROVIDER: | scopus |
| PUBMED: | 22203755 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 1 March 2012" - "CODEN: JCOND" - "Source: Scopus" |
