Online first
Review paper
Published online: 2025-01-24
Safety of combination therapy with olaparib and bevacizumab in the maintenance treatment of a patients with newly diagnosed ovarian cancer
Abstract
Olaparib-bevacizumab combination therapy has been included in the drug program for the maintenance treatment of patients with newly diagnosed ovarian cancer (B.50). Patients with BRCA gene mutation and/or homologous recombination deficiency (HRD) are eligible for the drug program. Both drug products have an acceptable safety profile but have so far been used separately — in monotherapy. Combination therapy appears to be an effective and safe solution and a new option for maintenance treatment of patients with advanced ovarian cancer.
Keywords: PAOLAolaparibbevacizumabovarian cancersafety
References
- Astra Zeneca Phrarmaceuticals, Lynparza Tablets Digital Presciber Information Placeholder, last accessed January 8th, 2024. https://www.lynparza.co.uk/content/dam/open-digital/lynparza/en/landing-page/ni-pi-lynparza-tablets.pdf.
- Ledermann J, Harter P, Gourley C, et al. Olaparib Maintenance Therapy in Patients With Platinum-Sensitive Relapsed Serous Ovarian Cancer. Obstet Gynecol Surv. 2014; 69(10): 594–596.
- Pujade-Lauraine E, Ledermann JA, Selle F, et al. SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017; 18(9): 1274–1284.
- Moore K, Colombo N, Scambia G, et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018; 379(26): 2495–2505.
- Agencja Oceny Technologii Medycznych i Taryfikacji.
- Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021; 22(12): 1721–1731.
- Monk BJ, Coleman RL, Fujiwara K, et al. ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA-MONO) and rucaparib in combination with nivolumab (ATHENA-COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer. Int J Gynecol Cancer. 2021; 31(12): 1589–1594.
- Del Campo JM, Matulonis UA, Malander S, et al. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019; 37(32): 2968–2973.
- González-Martín A, Pothuri B, Vergote I, et al. PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019; 381(25): 2391–2402.
- Mateo J, Moreno V, Gupta A, et al. An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib. Target Oncol. 2016; 11(3): 401–415.
- Charakterystyka Produktu Leczniczego, Pfizer Aneks i Charakterystyka Produktu Leczniczego 1 BioNTech Comirnaty Pfizer. 2AD, 1–156.
- Coleman RL, Fleming GF, Brady MF, et al. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med. 2019; 381(25): 2403–2415.
- DiSilvestro P, Banerjee S, Colombo N, et al. 517O Overall survival (OS) at 7-year (y) follow-up (f/u) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) who received maintenance olaparib in the SOLO1/GOG-3004 trial. Ann Oncol. 2022; 33: S779.
- Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008; 8(8): 579–591.
- Han ES, Wakabayashi M, Leong L. Angiogenesis inhibitors in the treatment of epithelial ovarian cancer. Curr Treat Options Oncol. 2013; 14(1): 22–33.
- Burger RA, Sill MW, Monk BJ, et al. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007; 25(33): 5165–5171.
- Aghajanian C, Blank SV, Goff BA, 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. J Clin Oncol. 2012; 30(17): 2039–2045.
- Pujade-Lauraine E, Hilpert F, Weber B, et al. AURELIA: A randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC). J Clin Oncol. 2012; 30(15_suppl): LBA5002–LBA5002.
- Burger RA, Brady MF, Bookman MA, et al. Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011; 365(26): 2473–2483.
- Colomban O, Tod M, Peron J, et al. Bevacizumab for Newly Diagnosed Ovarian Cancers: Best Candidates Among High-Risk Disease Patients (ICON-7). JNCI Cancer Spectr. 2020; 4(3): pkaa026.
- Perren TJ, Swart AM, Pfisterer J, et al. ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011; 365(26): 2484–2496.
- McCann KE. Novel poly-ADP-ribose polymerase inhibitor combination strategies in ovarian cancer. Curr Opin Obstet Gynecol. 2018; 30(1): 7–16.
- Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 2008; 8(8): 592–603.
- Chan N, Bristow RG. "Contextual" synthetic lethality and/or loss of heterozygosity: tumor hypoxia and modification of DNA repair. Clin Cancer Res. 2010; 16(18): 4553–4560.
- Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science. 2017; 355(6330): 1152–1158.
- Pommier Y, O'Connor MJ, de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci Transl Med. 2016; 8(362): 362ps17.
- Bindra RS, Crosby ME, Glazer PM. Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev. 2007; 26(2): 249–260.
- Bindra RS, Schaffer PJ, Meng A, et al. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol. 2004; 24(19): 8504–8518.
- Alvarez Secord A, O'Malley DM, Sood AK, et al. Rationale for combination PARP inhibitor and antiangiogenic treatment in advanced epithelial ovarian cancer: A review. Gynecol Oncol. 2021; 162(2): 482–495.
- Lim JJ, Yang K, Taylor-Harding B, et al. VEGFR3 inhibition chemosensitizes ovarian cancer stemlike cells through down-regulation of BRCA1 and BRCA2. Neoplasia. 2014; 16(4): 343–53.e1.
- Wei W, Li Y, Lv S, et al. PARP-1 may be involved in angiogenesis in epithelial ovarian cancer. Oncol Lett. 2016; 12(6): 4561–4567.
- Tentori L, Lacal PM, Muzi A, et al. Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. Eur J Cancer. 2007; 43(14): 2124–2133.
- Genentech I. Highlights of Prescribing Information for Avastin. 2019, 43.
- Panoilia E, Schindler E, Samantas E, et al. A pharmacokinetic binding model for bevacizumab and VEGF165 in colorectal cancer patients. Cancer Chemother Pharmacol. 2015; 75(4): 791–803.
- Liu JF, Barry WT, Birrer M, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014; 15(11): 1207–1214.
- Mirza MR, Åvall Lundqvist E, Birrer MJ, et al. AVANOVA investigators. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol. 2019; 20(10): 1409–1419.
- Ray-Coquard I, Pautier P, Pignata S, et al. PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019; 381(25): 2416–2428.
- Colombo N, Moore K, Scambia G, et al. Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial. Gynecol Oncol. 2021; 163(1): 41–49.
- Colombo N, Moore K, Scambia G, et al. Adverse events (AEs) with maintenance olaparib in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Phase III SOLO1 trial. J Clin Oncol. 2019; 37(15_suppl): 5539–5539.
- LYNPARZA® (Olaparib) [Prescribing Information]. Wilmington, AstraZeneca Pharm. LP; 2022.
- Ray-Coquard I, Leary A, Pignata S, et al. PAOLA-1/ENGOT-ov25 investigators. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023; 34(8): 681–692.
- Ray-Coquard IL, Leary A, Pignata S, et al. LBA29 Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC). Ann Oncol. 2022; 33: S1396–S1397.
- Harter P, Mouret-Reynier MA, Pignata S, et al. Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial. Gynecol Oncol. 2022; 164(2): 254–264.
- Sabatier R, Rousseau F, Joly F, et al. Efficacy and safety of maintenance olaparib and bevacizumab in ovarian cancer patients aged ≥65 years from the PAOLA-1/ENGOT-ov25 trial. Eur J Cancer. 2023; 181: 42–52.
- Montégut C, Falandry C, Cinieri S, et al. 167 Safety and quality of life of first-line maintenance olaparib plus bevacizumab in older patients with advanced ovarian cancer in the PAOLA-1 trial. Int J Gynecol Cancer. 2021; 31: A201–A202.
- Fujiwara K, Fujiwara H, Yoshida H, et al. Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial. J Gynecol Oncol. 2021; 32(5): e82.
- Friedlander M, Lee YC, Tew WP. Managing Adverse Effects Associated With Poly (ADP-ribose) Polymerase Inhibitors in Ovarian Cancer: A Synthesis of Clinical Trial and Real-World Data. Am Soc Clin Oncol Educ Book. 2023; 43: e390876.
- Rolfo C, Isambert N, Italiano A, et al. Pharmacokinetics and safety of olaparib in patients with advanced solid tumours and mild or moderate hepatic impairment. Br J Clin Pharmacol. 2020; 86(9): 1807–1818.
- Rolfo C, de Vos-Geelen J, Isambert N, et al. Pharmacokinetics and Safety of Olaparib in Patients with Advanced Solid Tumours and Renal Impairment. Clin Pharmacokinet. 2019; 58(9): 1165–1174.
- Kurtz J, Anota A, Cropet C, et al. Quality of life in patients with advanced high-grade ovarian cancer (HGOC) receiving maintenance therapies after first-line (1L) chemotherapy in the randomized phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644). J Clin Oncol. 2022; 40(16_suppl): 5560–5560.
- Joly F, Chabaud S, Cropet C, et al. Time without symptoms or toxicity (TWiST) in patients with newly diagnosed advanced ovarian cancer receiving maintenance olaparib or placebo plus bevacizumab: Analysis of PAOLA-1/ENGOT-ov25 phase III trial. J Clin Oncol. 2022; 40(16_suppl): 5562–5562.