Efficacy and safety of combination of poly-ADP-ribose polymerase inhibitor (PARPi) and chemotherapy compared with chemotherapy alone in treatment of recurrent ovarian carcinoma: a systematic review.
Main Article Content
Keywords
Ovarian Cancer, Safety, Efficacy, Chemotherapy, Combined PARP Inhibitor
Abstract
Platinum-based chemotherapy after surgical cytoreduction is the universal treatment for advanced ovarian cancer (OC), however, about eighty percent of patients experienced relapse and progression-free survival remained poor. Patients who relapsed within one year of treatment eventually become resistant to second-line chemotherapy. Poly-ADP-ribose polymerase inhibitors are a novel class of targeted therapy that could overcome these challenges by augmenting the chemotherapeutic activity of other cytotoxic agents. Cumulative Index to Nursing and Allied Health Literature (CINHAL), Cochrane and PubMed databases were searched for potentially relevant primary publications from 2011 to 2022 reporting on efficacy and safety of combination of a PARP inhibitor and chemotherapy versus chemotherapy in recurrent OC and reviewed. The outcomes of interest assessed qualitatively were progression-free survival (PFS) and grade 3 or higher adverse events (AEs) as measures of efficacy and safety respectively. Eight randomized controlled trials (RCTs) were included in the systematic review comprising 3,021 patients evaluated efficacy and safety of PARP inhibitors: Olaparib, niraparib and veliparib with combinations of bevacizumab, carboplatin, cisplatin, cediranib, cyclophosphamide and paclitaxel. 824 patients had 33 BRCA mutation while 1,430 had wild-type BRCA, an allele that confers increased risk of cancer. Most patients had platinum-sensitive cancers. There was significant prolongation of PFS with PARP inhibitor and chemotherapy combination compared to chemotherapy in all included trials except one which combined veliparib with cyclophosphamide. The prolongation of PFS was more remarkable in patients with BRCA mutation and occasionally patients with wild-type BRCA. Niraparib and veliparib were notably associated with grade 3 or higher anaemia, neutropenia, and thrombocytopenia, olaparib caused fatigue and gastrointestinal disturbances while bevacizumab and cediranib caused hypertension. This review suggested combined PARP inhibitor and chemotherapy significantly prolonged progression-free survival especially in patients with BRCA mutation compared to chemotherapy and the combined therapy is safe.
References
2. Hao J, Liu Y, Zhang T, He J, Zhao H, An R, et al. Efficacy and safety of PARP inhibitors in the treatment of advanced ovarian cancer: An updated systematic review and meta-analysis of randomized controlled trials. Critical Reviews in Oncology/Hematology. 2020: 103145.doi: 10.1016/j.critrevonc.2020.103145.
3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2018;68(6): 394-424.doi: 10.3322/caac.21492.
4. Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. New England Journal of Medicine. 2019;381(25): 2416-28.doi: 10.1056/NEJMoa1911361.
5. Jiang Y, Zhao J, Zhang L, Tian S, Yang T, Wang L, et al. Evaluation of the Efficacy and Safety of PARP Inhibitors in Advanced-Stage Epithelial Ovarian Cancer. Frontiers in oncology. 2020; 10: 954.doi: 10.3389/fonc.2020.00954.
6. Cooke SL, Brenton JD. Evolution of platinum resistance in high-grade serous ovarian cancer. The lancet oncology. 2011;12(12): 1169-74.doi: 10.1016/S1470-2045(11)70123-1.
7. Mansouri A, McGregor N, Dunn R, Dobbie S, Holmes J, Collins L, et al. Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol. BMJ open. 2021;11(1): e041463. doi.org/10.1136/bmjopen-2020-041463
8. LaFargue CJ, Dal Molin GZ, Sood AK, Coleman RL. Exploring and comparing adverse events between PARP inhibitors. The Lancet Oncology. 2019;20(1): e15-e28.doi: 10.1016/S1470-2045(18)30786-1.
9. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. 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. 2014;15(8): 852-61.doi: 10.1016/S1470-2045(14)70228-1.
10. Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2017;390(10106): 1949-61.doi: 10.1016/S0140-6736(17)32440-6.
11. Patel A, Sarkaria J, Kaufmann S. Nonhomologous end-joining drives PARP inhibitor synthetic lethality in homologous recombination-deficient cells. Proc Natl Acad Sci USA. 2011 ; 108: 3406-11.doi: 10.1073/pnas.1013715108.
12. Mateo J, Lord C, Serra V, Tutt A, Balmaña J, Castroviejo-Bermejo M, et al. A decade of clinical development of PARP inhibitors in perspective. Annals of Oncology. 2019;30(9): 1437-47.doi: 10.1093/annonc/mdz192.
13. Zheng F, Zhang Y, Chen S, Weng X, Rao Y, Fang H. Mechanism, and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer. Biomedicine & Pharmacotherapy. 2020; 123: 109661.doi: 10.1016/j.biopha.2019.109661.
14. Haince J-F, McDonald D, Rodrigue A, Déry U, Masson J-Y, Hendzel MJ, et al. PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites. Journal of Biological Chemistry. 2008;283(2): 1197-208.doi: 10.1074/jbc.M706734200.
15. Frey MK, Pothuri B. Homologous recombination deficiency (HRD) testing in ovarian cancer clinical practice: a review of the literature. Gynecologic oncology research and practice. 2017;4(1): 1-11.doi: 10.1186/s40661-017-0039-8.
16. Network CGAR. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353): 609.doi: 10.1038/nature10166.
17. Oza AM, Matulonis UA, Malander S, Hudgens S, Sehouli J, Del Campo JM, et al. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. The Lancet Oncology. 2018;19(8): 1117-25.doi: 10.1016/S1470-2045(18)30333-4.
18. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. Journal of clinical oncology. 2015;33(3): 244.doi: 10.1200/JCO.2014.56.2728.
19. Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proceedings of the National Academy of Sciences. 2008;105(44): 17079-84.doi: 10.1073/pnas.0806092105.
20. Huang X-z, Jia H, Xiao Q, Li R-z, Wang X-s, Yin H-y, et al. Efficacy and Prognostic Factors for PARP Inhibitors in Patients with Ovarian Cancer. Frontiers in oncology. 2020; 10.doi: 10.3389/fonc.2020.00958.
21. Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, et al. A Phase 1 trial of the poly (ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer. 2013;49(14):2972-8. doi.org/10.1016/j.ejca.2013.05.020
22. Kaplan AR, Gueble SE, Liu Y, Oeck S, Kim H, Yun Z, et al. Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51. Science translational medicine. 2019;11(492).doi: 10.1126/scitranslmed. aav4508.
23. Kummar S, Ji J, Morgan R, Lenz H-J, Puhalla SL, Belani CP, et al. A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. Clinical Cancer Research. 2012;18(6): 1726-34.doi: 10.1158/1078-0432.CCR-11-2821.
24. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. Journal of Clinical Epidemiology. 2021; 134:103-12. doi.org/10.1016/j.jclinepi.2021.02.003
25. Health UDo, Services H. National Cancer Institute. Common Terminology Criteria for Adverse Events, version 4.0. 2009. 2014. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5x11.pdf
26. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled clinical trials. 1996;17(1):1-12. d doi.org/10.1016/0197-2456(95)00134-4
27. Mirza MR, Lundqvist EÅ, Birrer MJ, Christensen Rd, Nyvang G-B, Malander S, et al. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. The Lancet Oncology. 2019;20(10): 1409-19.doi: 10.1016/S1470-2045(19)30515-7.
28. Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. The lancet oncology. 2015;16(1): 87-97.doi: 10.1016/S1470-2045(14)71135-0.
29. Liu J, Barry W, Birrer M, Lee J-M, Buckanovich R, Fleming G, et al. Overall survival, and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. Annals of Oncology. 2019;30(4): 551-7.doi: 10.1093/annonc/mdz018.
30. Colombo N, Nicoletto M, Panici PB, Tognon G, Bologna A, Lissoni A, et al. BAROCCO: A randomized phase II study of weekly paclitaxel vs cediranib-olaparib combination given with continuous or intermittent schedule in patients with recurrent platinum resistant ovarian cancer (PROC). Annals of Oncology. 2019;30: v896. doi.org/10.1093/annonc/mdz394.055
31. Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, et al. A phase III study comparing single-agent olaparib or the combination of cediranib and olaparib to standard platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer. American Society of Clinical Oncology; 2020. doi/abs/10.1200/JCO.2020.38.15
32. Kummar S, Oza AM, Fleming GF, Sullivan DM, Gandara DR, Naughton MJ, et al. Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer. Clinical cancer research. 2015;21(7): 1574-82.doi: 10.1158/1078-0432.
33. Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. New England Journal of Medicine. 2019;381(25): 2403-15.doi: 10.1056/NEJMoa1909707.
34. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005 ;434(7035) : 917-21.doi: 10.1038/nature03445.
35. Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, et al. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. Journal of Clinical Oncology. 2006;24(29): 4699-707.doi: 10.1200/JCO.2006.06.0913.
36. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. New England Journal of Medicine. 2012;366(15): 1382-92.doi: 10.1056/NEJMoa1105535.
37. Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. 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. 2011;12(9):852-61. doi.org/10.1016/S1470-2045(11)70214-5
38. Matulonis UA, Berlin S, Ivy P, Tyburski K, Krasner C, Zarwan C, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. Journal of clinical oncology. 2009;27(33): 5601.doi: 10.1200/JCO.2009.23.2777.
39. Moore K, Colombo N, Scambia G, Kim B-G, Oaknin A, Friedlander M, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. New England Journal of Medicine. 2018;379(26): 2495-505.doi: 10.1056/NEJMoa1810858.
40. Puhalla S, Beumer JH, Pahuja S, Appleman LJ, Tawbi HA-H, Stoller RG, et al. Final results of a phase 1 study of single-agent veliparib (V) in patients (pts) with either BRCA1/2-mutated cancer (BRCA+), platinum-refractory ovarian, or basal-like breast cancer (BRCA-wt). American Society of Clinical Oncology; 2014. doi: 10.1200/jco.2014.32.15
41. Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2012;30(17): 2039-45.doi: 10.1200/JCO.2012.42.0505.
42. Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, et al. Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. The Lancet Oncology. 2017;18(6): 779-91.doi: 10.1016/S1470-2045(17)30279-6.
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