IJMPCERO  Vol.4 No.4 , November 2015
Impact of Olaparib for Maintenance Monotherapy on Survival in Breast and Ovarian Cancer: A Systematic Review and Pooled Analysis of Published Trials
Abstract: Purpose: To assess the efficacy and safety of Olaparib, a PARP inhibitor on progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) in patients with breast and ovarian cancer. Methods: Research data from clinical trials through PubMed, Science Citation Index, Elsevier Science Direct and Cochrane Library of all published studies exploring the PFS, ORR or OS of Olaparib for maintenance monotherapy on survival in breast and ovarian cancer were analysed. Pooled estimates of the ORR, weighted medians of PFS and OS from all Olaparib were calculated. Assessment of quality and level of evidence was assigned by Cochrane guidelines and guidelines of Oxford Centre for Evidence-Based Medicine. Results: Data of 893 patients (731 olaparib; 162 control) from 6 trials, 2 randomised controlled trials and 4 non-randomised trials, were included. The overall median weighted PFS and OS in patients treated with Olaparib were 5.9 and 19.1 months, respectively. The pooled ORR was 25%. Olaparib showed a greater effect on PFS in patients with both wild-type BRCA and BRCA mutant gene. The most common toxicity were nausea and vomiting. Conclusions: Olaparib as maintenance monotherapy for breast and ovarian cancer is associated with promising outcomes including increased response rate and improved PFS. Its potential in clinical application is needed for further investigation in phase III trials.
Cite this paper: Dong, J. , Zhang, T. and Wen, B. (2015) Impact of Olaparib for Maintenance Monotherapy on Survival in Breast and Ovarian Cancer: A Systematic Review and Pooled Analysis of Published Trials. International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 4, 338-347. doi: 10.4236/ijmpcero.2015.44040.

[1]   Lynch, H.T., Casey, M.J., Snyder, C.L., et al. (2009) Hereditary Ovarian Carcinoma: Heterogeneity, Molecular Genetics, Pathology, and Management. Molecular Oncology, 3, 97-137.

[2]   Narod, S.A. (2011) Genetic Variants Associated with Breast-Cancer Risk. The Lancet Oncology, 12, 415-416.

[3]   Lord, C.J. and Ashworth, A. (2013) Mechanisms of Resistance to Therapies Targeting BRCA-Mutant Cancers. Nature Medicine, 19, 1381-1388.

[4]   Lee, J.M., Ledermann, J.A. and Kohn, E.C. (2014) PARP Inhibitors for BRCA1/2 Mutation-Associated and BRCA-Like Malignancies. Annals of Oncology, 25, 32-40.

[5]   Karginova, O., Siegel, M.B., Van Swearingen, A.E., et al. (2015) Efficacy of Carboplatin Alone and in Combination with ABT888 in Intracranial Murine Models of BRCA-Mutated and BRCA-Wild-Type Triple-Negative Breast Cancer. Molecular Cancer Therapeutics, 14, 920-930.

[6]   Rouleau, M., Patel, A., Hendzel, M.J., Kaufmann, S.H. and Poirier, G.G. (2010) PARP Inhibition: PARP1 and Beyond. Nature Reviews Cancer, 10, 293-301.

[7]   Shaw, H.M. and Hall, M. (2013) Emerging Treatment Options for Recurrent Ovarian Cancer: The Potential Role of Olaparib. OncoTargets and Therapy, 6, 1197-1206.

[8]   Yamamoto, N., Nokihara, H., Yamada, Y., et al. (2012) A Phase I, Dose-Finding and Pharmacokinetic Study of Olaparib (AZD2281) in Japanese Patients with Advanced Solid Tumors. Cancer Science, 103, 504-509.

[9]   Fong, P.C., Yap, T.A., Boss, D.S., et al. (2010) Poly(ADP)-Ribose Polymerase Inhibition: Frequent Durable Responses in BRCA Carrier Ovarian Cancer Correlating with Platinum-Free Interval. Journal of Clinical Oncology, 28, 2512-2519.

[10]   Fong, P.C., Boss, D.S., Yap, T.A., et al. (2009) Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers. The New England Journal of Medicine, 361, 123-134.

[11]   Marchetti, C., Imperiale, L., Gasparri, M.L., Palaia, I., Pignata, S., Boni, T., et al. (2012) Olaparib, PARP1 Inhibitor in Ovarian Cancer. Expert Opinion on Investigational Drugs, 21, 1575-1584.

[12]   Ledermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., et al. (2012) Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer. New England Journal of Medicine, 366, 1382-1392.

[13]   Audeh, M.W., Carmichael, J., Penson, R.T., Friedlander, M., Powell, B., Bell-McGuinn, K.M., et al. (2010) Oral Poly(ADP-ribose) Polymerase Inhibitor Olaparib in Patients with BRCA1 or BRCA2 Mutations and Recurrent Ovarian Cancer: A Proof-of-Concept Trial. The Lancet, 376, 245-251.

[14]   Tutt, A., Robson, M., Garber, J.E., Domchek, S.M., Audeh, M.W., Weitzel, J.N., et al. (2010) Oral Poly(ADP-ribose) Polymerase Inhibitor Olaparib in Patients with BRCA1 or BRCA2 Mutations and Advanced Breast Cancer: A Proof-of-Concept Trial. The Lancet, 376, 235-244.

[15]   Mahaney, B.L., Meek, K. and Lees-Miller, S.P. (2009) Repair of Ionizing Radiation-Induced DNA Double-Strand Breaks by Non-Homologous End-Joining. Biochemical Journal, 417, 639-650.

[16]   Jadad, A.R., Moore, R.A., Carroll, D., Jenkinson, C., Reynolds, D.J.M., Gavaghan, D.J. and McQuay, H.J. (1996) Assessing the Quality of Reports of Randomized Clinical Trials: Is Blinding Necessary? Controlled Clinical Trials, 17, 1-12.

[17]   Phillips, B., Ball, C., Sackett, D., Badenoch, D., Straus, S., Haynes, B. and Dawes, M. (2009) Oxford Centre for Evidence-Based Medicine—Levels of Evidence (March 2009).

[18]   Gelmon, K.A., Tischkowitz, M., Mackay, H., Swenerton, K., Robidoux, A., Tonkin, K., et al. (2011) 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. The Lancet Oncology, 12, 852-861.

[19]   Kaye, S.B., Lubinski, J., Matulonis, U., Ang, J.E., Gourley, C., Karlan, B.Y., et al. (2012) 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 of Clinical Oncology, 30, 372-379.

[20]   Kaufman, B., Shapira-Frommer, R., Schmutzler, R.K., Audeh, M.W., Friedlander, M., Balmaña, J., et al. (2015) Olaparib Monotherapy in Patients with Advanced Cancer and a Germline BRCA1/2 Mutation. Journal of Clinical Oncology, 33, 244-250.

[21]   Hall, M. and Rustin, G. (2011) Recurrent Ovarian Cancer: When and How to Treat. Current Oncology Reports, 13, 459-471.

[22]   Liu, J.F., Barry, W.T., Birrer, M., Lee, J.-M., Buckanovich, R.J., Fleming, G.F., et al. (2014) Combination Cediranib and Olaparib versus Olaparib Alone for Women with Recurrent Platinum-Sensitive Ovarian Cancer: A Randomised Phase 2 Study. The Lancet Oncology, 15, 1207-1214.

[23]   Ledermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., et al. (2014) Olaparib Maintenance Therapy in Patients with Platinum-Sensitive Relapsed Serous Ovarian Cancer: A Preplanned Retrospective Analysis of Outcomes by BRCA Status in a Randomised Phase 2 Trial. The Lancet Oncology, 15, 852-861.

[24]   Ledermann, J.A. and Raja, F.A. (2011) Clinical Trials and Decision-Making Strategies for Optimal Treatment of Relapsed Ovarian Cancer. European Journal of Cancer, 47, S104-S115.

[25]   Raja, F.A., Counsell, N., Colombo, N., Pfisterer, J., du Bois, A., Parmar, M.K., et al. (2013) Platinum versus Platinum-Combination Chemotherapy in Platinum-Sensitive Recurrent Ovarian Cancer: A Meta-Analysis Using Individual Patient Data. Annals of Oncology, 24, 3028-3034.

[26]   Monk, B.J., Herzog, T.J., Kaye, S.B., Krasner, C.N., Vermorken, J.B., Muggia, F.M., et al. (2010) Trabectedin plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer. Journal of Clinical Oncology, 28, 3107-3114.

[27]   Bayraktar, S. and Gluck, S. (2012) Systemic Therapy Options in BRCA Mutation-Associated Breast Cancer. Breast Cancer Research and Treatment, 135, 355-366.

[28]   Sandhu, S.K., Schelman, W.R., Wilding, G., Moreno, V., Baird, R.D., Miranda, S., et al. (2013) The Poly(ADP-ribose) Polymerase Inhibitor Niraparib (MK4827) in BRCA Mutation Carriers and Patients with Sporadic Cancer: A Phase 1 Dose-Escalation Trial. The Lancet Oncology, 14, 882-892.

[29]   O’Shaughnessy, J., Schwartzberg, L., Danso, M.A., Miller, K.D., Rugo, H.S., Neubauer, M., et al. (2014) Phase III Study of Iniparib plus Gemcitabine and Carboplatin versus Gemcitabine and Carboplatin in Patients with Metastatic Triple-Negative Breast Cancer. Journal of Clinical Oncology, 32, 3840-3847.

[30]   Moore, K.N., DiSilvestro, P. and Lowe, E.S. (2014) SOLO1 and SOLO2 Randomized Phase III Trials of Olaparib in Patients (pts) with Ovarian Cancer and a BRCA12 Mutation (BRCAm). ASCO Annual Meeting 2014, Chicago, 30 May-3 June 2014, TPS5616 [Abstract].