First evidence of olaparib maintenance therapy in patients with newly diagnosed homologous recombination deficient positive/BRCA wild-type ovarian cancer: a real-world multicenter study

Abstract

Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.

Keywords

adverse events / maintenance therapy / olaparib / ovarian cancer / progression-free survival

References

[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209–249

[2] Colombo N, Sessa C, Du Bois A, Ledermann J, McCluggage W, McNeish I, Morice P, Pignata S, Ray-Coquard I, Vergote I, Baert T, Belaroussi I, Dashora A, Olbrecht S, Planchamp F, Querleu D, Baert T, Banerjee S, Belaroussi I, Blecharz P, Bruchim I, Cibula D, Colombo N, Concin N, Davidson B, Dashora A, Devouassoux-Shisheboran M, du Bois A, Ferrero A, Glasspool R, González-Martin A, Heinzelmann-Schwarz V, Joly F, Kim JW, Kridelka F, Ledermann J, Lorusso D, Mahner S, McCluggage WG, McNeish I, Mikami M, Mirza MR, Morice P, Nicum S, Olbrecht S, O’Donnell DM, Pautier P, Planchamp F, Pignata S, Querleu D, Ray-Coquard I, Rodolakis A, Sehouli J, Selcukbiricik F, Sessa C, Singh N, Tan DSP, Timmerman D, Tognon G, van der Velden J, Vergote I, Witteveen PO, Zeimet AG. ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Ann Oncol 2019; 30(5): 672–705

[3] Ray-Coquard I, Pautier P, Pignata S, Perol D, Gonzalez-Martin A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med 2019; 381(25): 2416–2428

[4] González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O’Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2019; 381(25): 2391–2402

[5] Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA III, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med 2019; 381(25): 2403–2415

[6] Monk BJ, Parkinson C, Lim MC, O’Malley DM, Oaknin A, Wilson MK, Coleman RL, Lorusso D, Bessette P, Ghamande S, Christopoulou A, Provencher D, Prendergast E, Demirkiran F, Mikheeva O, Yeku O, Chudecka-Glaz A, Schenker M, Littell RD, Safra T, Chou HH, Morgan MA, Drochýtek V, Barlin JN, Van Gorp T, Ueland F, Lindahl G, Anderson C, Collins DC, Moore K, Marme F, Westin SN, McNeish IA, Shih D, Lin KK, Goble S, Hume S, Fujiwara K, Kristeleit RS. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol 2022; 40(34): 3952–3964

[7] Li N, Zhu J, Yin R, Wang J, Pan L, Kong B, Zheng H, Liu J, Wu X, Wang L, Huang Y, Wang K, Zou D, Zhao H, Wang C, Lu W, Lin A, Lou G, Li G, Qu P, Yang H, Zhen X, Hang W, Hou J, Wu L. Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME Study): a randomized, double-blind, placebo-controlled, phase 3 trial (LBA 5). Gynecol Oncol 2022; 166(Supplement 1): S50–S51

[8] Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018; 379(26): 2495–2505

[9] Tew WP, Lacchetti C, Kohn EC. Poly(ADP-Ribose) polymerase inhibitors in the management of ovarian cancer: ASCO guideline rapid recommendation update. J Clin Oncol 2022; 40(33): 3878–3881

[10] Armstrong DK, Alvarez RD, Backes FJ, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, Chen L, Chitiyo VC, Cristea M, DeRosa M, Eisenhauer EL, Gershenson DM, Gray HJ, Grisham R, Hakam A, Jain A, Karam A, Konecny GE, Leath CA III, Leiserowitz G, Liu J, Martin L, Matei D, McHale M, McLean K, Miller DS, Percac-Lima S, Remmenga SW, Schorge J, Stewart D, Thaker PH, Vargas R, Hendrickson AW, Werner TL, Zsiros E, Dwyer MA, Hang L. NCCN Guidelines(R) insights: ovarian cancer, version 3.2022. J Natl Compr Canc Netw 2022; 20(9): 972–980

[11] Kim G, Ison G, McKee AE, Zhang H, Tang S, Gwise T, Sridhara R, Lee E, Tzou A, Philip R, Chiu HJ, Ricks TK, Palmby T, Russell AM, Ladouceur G, Pfuma E, Li H, Zhao L, Liu Q, Venugopal R, Ibrahim A, Pazdur R. FDA approval summary: olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy. Clin Cancer Res 2015; 21(19): 4257–4261

[12] Armstrong DK, Alvarez RD, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, Berek JS, Chen L, Cristea M, DeRosa M, ElNaggar AC, Gershenson DM, Gray HJ, Hakam A, Jain A, Johnston C, Leath CA III, Liu J, Mahdi H, Matei D, McHale M, McLean K, O’Malley DM, Penson RT, Percac-Lima S, Ratner E, Remmenga SW, Sabbatini P, Werner TL, Zsiros E, Burns JL, Engh AM. NCCN Guidelines insights: ovarian cancer, version 1.2019. J Natl Compr Canc Netw 2019; 17(8): 896–909

[13] DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, McNamara J, Lowe ES, Ah-See ML, Moore KN. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: the SOLO1/GOG 3004 trial. J Clin Oncol 2023; 41(3): 609–617

[14] Li N, Zhu J, Yin R, Wang J, Pan L, Kong B, Zheng H, Liu J, Wu X, Wang L, Huang Y, Wang K, Zou D, Zhao H, Wang C, Lu W, Lin A, Lou G, Li G, Qu P, Yang H, Zhang Y, Cai H, Pan Y, Hao M, Liu Z, Cui H, Yang Y, Yao S, Zhen X, Hang W, Hou J, Wang J, Wu L. Treatment with niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer: a phase 3 randomized clinical trial. JAMA Oncol 2023; 9(9): 1230

[15] Banerjee S, Moore K, Colombo N, Scambia G, Kim B, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, Martín AG, Aghajanian C, Bradley W, Holmes E, Lowe ES, DiSilvestro P. 811MO maintenance olaparib for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1. Ann Oncol 2020; 31(Supplement 4): S613

[16] Bradley W, Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke G, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Cain T, Lowe E, DiSilvestro P. Maintenance olaparib for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO1. Gynecol Oncol 2021; 162(Supplement 1): S25–S26

[17] Chambers LM, O’Malley DM, Coleman RL, Herzog TJ. Is there a “low-risk” patient population in advanced epithelial ovarian cancer?: a critical analysis. Am J Obstet Gynecol 2022; 227(5): 728–734

[18] Banerjee S, Gonzalez-Martin A, Harter P, Lorusso D, Moore KN, Oaknin A, Ray-Coquard I. First-line PARP inhibitors in ovarian cancer: summary of an ESMO Open—cancer horizons round-table discussion. ESMO Open 2020; 5(6): e001110

[19] Gulia S, Kannan S, Ghosh J, Rath S, Maheshwari A, Gupta S. Maintenance therapy with a poly(ADP-ribose) polymerase inhibitor in patients with newly diagnosed advanced epithelial ovarian cancer: individual patient data and trial-level meta-analysis. ESMO Open 2022; 7(5): 100558

[20] Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; 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

[21] Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol 2016; 17(11): 1579–1589

[22] Gao Q, Zhu J, Zhao W, Huang Y, An R, Zheng H, Qu P, Wang L, Zhou Q, Wang D, Lou G, Wang J, Wang K, Low J, Kong B, Rozita AM, Sen LC, Yin R, Xie X, Liu J, Sun W, Su J, Zhang C, Zang R, Ma D. Olaparib maintenance monotherapy in Asian patients with platinum-sensitive relapsed ovarian cancer: phase III trial (L-MOCA). Clin Cancer Res 2022; 28(11): 2278–2285

[23] Wu L, Zhu J, Yin R, Wu X, Lou G, Wang J, Gao Y, Kong B, Lu X, Zhou Q, Wang Y, Chen Y, Lu W, Li W, Cheng Y, Liu J, Ma X, Zhang J. Olaparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation: SOLO1 China cohort. Gynecol Oncol 2021; 160(1): 175–181

[24] Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012; 366(15): 1382–1392

[25] Eakin CM, Ewongwo A, Pendleton L, Monk BJ, Chase DM. Real world experience of poly (ADP-ribose) polymerase inhibitor use in a community oncology practice. Gynecol Oncol 2020; 159(1): 112–117

[26] AstraZeneca PharmaceuticalsL. Lynparza (Olaparib) Capsules (Prescribing Information). AstraZeneca Pharmaceuticals LP, Wilmington, DE 2017

[27] Francis KE, Kim SI, Friedlander M, Gebski V, Ray-Coquard I, Clamp A, Penson RT, Oza A, Perri T, Huzarski T, Martin-Lorente C, Cecere SC, Colombo N, Ataseven B, Fujiwara K, Sonke G, Vergote I, Pujade-Lauraine E, Kim JW, Lee CK. The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer. Ann Oncol 2022; 33(6): 593–601

[28] Chen D, Shao M, Meng P, Wang C, Li Q, Cai Y, Song C, Wang X, Shi T. GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing. BMC Bioinformatics 2021; 22(1): 562

[29] Wen H, Feng Z, Ma Y, Liu R, Ou Q, Guo Q, Shen Y, Wu X, Shao Y, Bao H, Wu X. Homologous recombination deficiency in diverse cancer types and its correlation with platinum chemotherapy efficiency in ovarian cancer. BMC Cancer 2022; 22(1): 550

[30] Yuan W, Ni J, Wen H, Shi W, Chen X, Huang H, Zhang X, Lu X, Zhu C, Dong H, Yang S, Wu X, Chen X. Genomic Scar Score: a robust model predicting homologous recombination deficiency based on genomic instability. BJOG 2022; 129(Suppl 2): 14–22

[31] Chen Y, Wang X, Du F, Yue J, Si Y, Zhao X, Cui L, Zhang B, Bei T, Xu B, Yuan P. Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer. Cancer Biol Med 2023; 20(2): 155–168

[32] Huang K, Wang J, Yang B, Bai Y, Zhao X. 1206P Computing HRD score by a capture-based NGS panel reveal its prevalence in Chinese breast, ovarian, prostate and pancreatic cancer patients. Ann Oncol 2020; 31: S790

RIGHTS & PERMISSIONS

Higher Education Press