PARP inhibitors in ovarian cancer: Evidence, experience and clinical potential

Therapeutic Advances in Medical Oncology

Volumn 9, Issue 4, 2017, Pages 253-267

  Evans, Tarra ^a   Matulonis, Ursula ^b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

BRCA mutations; ovarian cancer; PARP inhibitors; targeted therapy

Indexed keywords

CARBOPLATIN; CEDIRANIB; DURVALUMAB; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; NIRAPARIB; OLAPARIB; PEMBROLIZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; RUCAPARIB; TALAZOPARIB; TICILIMUMAB; VELIPARIB;

ACUTE MYELOID LEUKEMIA; ANEMIA; ANOREXIA; BLOOD TOXICITY; CANCER CHEMOTHERAPY; CANCER RECURRENCE; DNA DAMAGE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERANCE; FATIGUE; GASTROINTESTINAL SYMPTOM; GENE EXPRESSION; GENE MUTATION; HUMAN; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; OVARY CARCINOMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; TASTE DISORDER; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUMOR GENE; VOMITING;

EID: 85018287348     PISSN: 17588340     EISSN: 17588359     Source Type: Journal    
DOI: 10.1177/1758834016687254     Document Type: Review

References (57)

1. Audeh M., Carmichael J., Penson R., Friedlander M., Powell B., Bell-McGuinn K., 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. Lancet 376: 245-251.
2. Bajrami I., Frankum J., Konde A., Miller R., Rehman F., Brough R., et al. (2014) Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity. Cancer Res 74: 287-297.
3. Bell-McGuinn K., Brady W., Schilder R., Fracasso P., Moore K., Walker J., et al. (2015) A phase I study of continuous veliparib in combination with IV carboplatin/paclitaxel or IV/IP paclitaxel/cisplatin and bevacizumab in newly diagnosed patients with previously untreated epithelial ovarian, fallopian tube, or primary peritoneal cancer: an NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol 33: abstract 5507.
4. Bryant H., Schultz N., Thomas H., Parker K., Flower D., Lopez E., et al. (2005). Specific killing of BRCA2-deficient tumours with inhibitors of poly (ADP-ribose) polymerase. Nature 434: 913-917.
5. Cancer Genome Atlas Research Network. (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474: 609-615.
6. Coleman R., Sill M., Bell-McGuinn K., Aghajanian C., Gray H, Tewari K., et al. (2015) A phase II evaluation of the potent, hightly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation-an NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol 137: 386-391.
7. Dean E., Middleton M., Pwint T., Swaisland H., Carmichael J., Goodege-Kunwar P., et al. (2012) Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. Br J Cancer 106: 468-474.
8. Drew Y., Ledermann J., Hall G., Rea D., Glasspool R., Highley M., et al. (2016) Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer. Br J Cancer 114: 723-730.
9. Farmer H., McCabe N., Lord C., Tutt A., Johnson D., Richardson T., et al. (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434: 917-921.
10. Fong P., Boss D., Yap T., Tutt A., Wu P., Mergui-Roelvink M., et al. (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361: 123-134.
11. Gelmon K., 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. Lancet Oncol 12: 852-861.
12. Higuchi T., Flies D., Marjon N., Mantia-Smaldone G., Ronner L., Gimotty P., et al. (2015) CTLA4 Blockade synergizes therapeutically with PARP inhibition in BRCA1-deficient ovarian cancer. Cancer Immunol Res 3: 1257-1268.
13. Huang J., Wang L., Cong Z., Amoozgar Z., Kiner E., Xing D., et al. (2015) The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian cancer. Biochem Biophys Res Commun 463: 551-556.
14. Ibrahim Y., García-García C., Serra V., He L., Torres-Lockhart K., Prat A., et al. (2012) PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition. Cancer Discov 2: 1036-1047.
15. Juvekar A., Burga L., Hu H., Lunsford E., Ibrahim Y., Balmañà J., et al. (2012) Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer. Cancer Discov 2: 1048-1063.
16. Kaufman B., Shapira-Frommer R., Schmutzler R., Audeh M., Friedlander M., Balmaña J., et al.(2015) Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33: 244-250.
17. Kaye S., Lubinski J., Matulonis U., Ang J., Gourley C., Karlan B., 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. J Clin Oncol 30: 372-379.
18. Konstantinopoulos P., Ceccaldi R., Shapiro G., D'Andrea A., (2015) Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov 5: 1137-1154.
19. Konstantinopoulos P., Moore K., Sachdev J., Mita M., Vinayak S., Seward S., et al. (2016) Phase I/II study of niraparib plus pembrolizumab in patients with triple-negative breast cancer or recurrent ovarian cancer (KEYNOTE-162). J Clin Oncol 34: abstract TPS5599.
20. Kristeleit R., Shapira-Frommer R., Burris H., Patel M., Lorusso P., Oza A., et al. (2014) Phase 1/2 study of oral rucaparib: updated phase 1 and preliminary phase 2 results. Ann Oncol 25: iv305-iv326.
21. Kristeleit R., Swisher E., Oza A., Coleman R., Scott C., Konecny G., et al. (2015) Final results of ARIEL2 (Part 1): a phase 2 trial to prospectively identify ovarian cancer (OC) responders to rucaparib using tumor genetic analysis. Eur J Can 51: S531.
22. Kummar S., Oza A., Fleming G., Sullivan D., Gandara D., Naughton M., et al. (2015) Randomized trial of oral cyclophosphamide and Veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer. Clin Cancer Res 21: 1574-1582.
23. Landrum L., Brady W., Armstrong D., Moore K., DiSilvestro P., O'Malley D., et al. (2016) A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: an NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol 140: 204-209.
24. Ledermann J., Harter P., Gourley C., Friedlander M., Vergote I., Rustin G., et al. (2012) Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366: 1382-1392.
25. 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. Lancet Oncol 15: 852-861.
26. Ledermann J., Harter P., Gourley C., Friedlander M., Vergote I., Rustin G., et al. (2016) Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving Olaparib maintenance monotherapy: an updated analysis from a randomized, placebo-controlled double-blind, phase 2 trial. Lancet Oncol 17: 1579-1589.
27. Lee J., Hays J., Annunziata C., Noonan A., Minasian L., Zujewski J., et al. (2014) Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. J Natl Cancer Inst 106: dju089.
28. Lord C., Ashworth A., (2013) Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat Med 19: 1381-1388.
29. Liu J., Barry W., Birrer M., Lee J., Buckanovich R., Fleming G., et al. (2014 a) Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol 15: 1207-1214.
30. Liu J., Konstantinopoulos P., Matulonis U., (2014 b) PARP inhibitors in ovarian cancer: current status and future promise. Gynecol Oncol 133: 362-369.
31. Liu J., Matulonis U., (2016) What is the place of PARP inhibitors in ovarian cancer treatment? Curr Oncol Rep 18: 29.
32. Liu J., Tolaney S., Birrer M., Fleming G., Buss M., Dahlberg S., et al. (2013) 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 49: 2972-2978.
33. Mateo J., Moreno V., Gupta A., Kaye S., Dean E., Middleton M., et al. (2016) An adaptive study to determine the optimal dose of the tablet formulation of the PARP inhibitor Olaparib. Target Oncol 11: 401-415.
34. Matulonis U., Harter P., Gourley C., Friedlander M., Vergote I., Rustin G., et al. (2016 a) Olaparib maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and BRCA mutation: overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy. Cancer 122: 1844-1852.
35. Matulonis U., Penson R., Domchek S., Kaufman B., Shapira-Frommer R., Audeh M., et al. (2016 b) Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol 27: 1013-1019.
36. Matulonis U., Wulf G., Barry W., Birrer M., Westin S., Spagnoletti T., et al. (2015) Phase 1 of oral BKM120 or BYL719 and olaparib for high-grade serous ovarian cancer or tirple-negative breast cancer: final results of the BKM120 plus olaparib cohort. Cancer Res 75: abstract CT324.
37. Matulonis U., Monk B., (2017) PARP inhibitor and chemotherapy combination trials fro the treatment of advanced malignancies: does a development pathway forward exist? Annals of Oncology. 28: 443-447.
38. Michalarea V., Lorente D., Lopez J., Carreira S., Hassam H., Parmar M., et al. (2015) Accelerated phase I trial of two schedules of the combination of the PARP inhibitor olaparib and AKT inhibitor AZD5363 using a novel intrapatient dose escalation design in advanced cancer patients. Cancer Res 75: abstract CT 323.
39. Miller R., Ledermann J., (2016) The status of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in ovarian cancer, part 1: Olaparib. Clin Adv Hematol Oncol 14: 619-627.
40. Mirza M., Monk B., Herrstedt J., Oza A., Mahner S., Redondo A., et al. (2016) Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375: 2154-2164.
41. Moore K., DiSilvestro P., Lowe E., Garnett S., Pujard-Lauraine E., (2014) SOLO1 and SOLO2: Randomized phase III trials of olaparib in patients (pts) with ovarian cancer and a BRCA1/2 mutation (BRCAm). J Clin Oncol 32: abstract TPS5616.
42. Moore K., Monk B., (2016) Patient counseling and management of symptoms during olaparib therapy for recurrent ovarian cancer. Oncologist 21: 954-963.
43. Murai J., Huang S., Das B., Renaud A., Zhang Y., Doroshow J., et al. (2012) Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res 72: 5588-5599.
44. Murai J., Huang S., Renaud A., Zhang Y., Ji J., Takeda S., et al. (2014) Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther 13: 433-443.
45. Oza A., Cibula D., Benzaquen A., Poole C., Mathijssen R., Sonke G., et al. (2015) Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol 16: 87-97.
46. Pardoll D., (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12: 252-264.
47. Pennington K., Walsh T., Harrell M., Lee M., Rendi M., Thornton A., et al. (2014) Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res 20: 764-775.
48. Plummer E., Calvert H., (2007) Targeting poly (ADP-ribose) polymerase: a two-armed strategy for cancer therapy. Clin Cancer Res 13: 6252-6256.
49. Sandhu S., Schelman W., Wilding G., Moreno V., Baird R., 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. Lancet Oncol 14: 882-892.
50. Sato E., Olson S., Ahn J., Bundy B., Nishikawa H., Qian F., et al. (2005) Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 102: 18538-18543.
51. Shen Y., Rehman F., Feng Y., Boshuizen J., Bajrami I., Elliott R., et al. (2013) BMN 673 a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res 19: 5003-5015.
52. Stover E., Konstantinopoulos P., Matulonis U., Swisher E., (2016) Biomarkers of response and resistance to DNA repair targeted therapies. Clin Cancer Res 22: 5651-5660.
53. Swisher E. M., Lin K. K., Oza A. M., Scott C. L., Giordano H., Sun. J., et al. (2016) Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre open-label, phase 2 trial. Lancet Oncology 2016.
54. US Food and Drug Administration. (2014) Oncologic Drugs Advisory Committee Meeting Announcement. FDA. Available at: http://www.fda.gov/AdvisoryCommittees/Calendar/ucm394126.htm.
55. Wang D., Li C., Zhang Y., Wang M., Jiang N., Xiang L., et al. (2016 a) Combined inhibition of PI3K and PARP is effective in the treatment of ovarian cancer cells with wild-type PIK3CA genes. Gynecol Oncol 142: 548-556.
56. Wang D., Wang M., Jiang N., Zhang Y., Bian X., Wang X., et al. (2016 b) Effective use of PI3K inhibitor BKM120 and PARP inhibitor olaparib to treat PIK3CA mutant ovarian cancer. Oncotarget 7: 13153-13166.
57. Zhang L., Conejo-Garcia J., Katsaros D., Gimotty P., Massobrio M., Regnani G., et al. (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348: 203-213.