Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA)

Qinglei Gao, Jianqing Zhu, Weidong Zhao, Yi Huang, Ruifang An, Hong Zheng, Pengpeng Qu, Li Wang, Qi Zhou, Danbo Wang, Ge Lou, Jing Wang, Ke Wang, John Low, Beihua Kong, Abdul Malik Rozita, Lim Chun Sen, Rutie Yin, Xing Xie, Jihong Liu, Wei Sun, Jingya Su, Chunyi Zhang, Rongyu Zang, Ding Ma, Qinglei Gao, Jianqing Zhu, Weidong Zhao, Yi Huang, Ruifang An, Hong Zheng, Pengpeng Qu, Li Wang, Qi Zhou, Danbo Wang, Ge Lou, Jing Wang, Ke Wang, John Low, Beihua Kong, Abdul Malik Rozita, Lim Chun Sen, Rutie Yin, Xing Xie, Jihong Liu, Wei Sun, Jingya Su, Chunyi Zhang, Rongyu Zang, Ding Ma

Abstract

Purpose: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer.

Patients and methods: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453).

Results: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs.

Conclusions: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.

©2022 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
Patient disposition.
Figure 2.
Figure 2.
Kaplan–Meier estimates of PFS (full analysis set). A, Overall analysis and B, subgroup analysis of BRCA mutation type. Primary efficacy analysis was performed after 139 investigator-assessed events of disease progression or death (60.7% of patients had disease progression, n = 136; 1.3% died prior to disease progression, n = 3). CI, confidence interval; NE, not evaluable.

References

    1. Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet 2009;374:1371–82.
    1. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. . Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012;366:1382–92.
    1. Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, et al. . Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol 2010;28:3323–9.
    1. 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. J Clin Oncol 2006;24:4699–707.
    1. Patel AG, Sarkaria JN, Kaufmann SH. Nonhomologous end joining drives poly (ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc Natl Acad Sci USA 2011;108:3406–11.
    1. 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. Biomed Pharmacother 2020;123:109661.
    1. Lynparza [package insert]. AstraZeneca. Wilmington, DE: 2014.
    1. Bochum S, Berger S, Martens UM. Olaparib. Recent Results Cancer Res 2018;211:217–33.
    1. Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, et al. . Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomized, placebo-controlled, phase III trial. Lancet Oncol 2017;18:1274–84.
    1. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, et al. . Niraparib maintenance therapy in platinum-sensitive recurrent ovarian cancer. N Engl J Med 2016;375:2154–64.
    1. 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 randomized, double-blind, placebo-controlled, phase III trial. Lancet 2017;390:1949–61.
    1. Wu XH, Zhu JQ, Yin RT, Yang JX, Liu JH, Wang J, et al. . Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol 2021;32:512–21.
    1. Li N, Zhang Y, Wang J, Zhu J, Wang L, Wu X, et al. . Fuzuloparib maintenance therapy in patients with platinum-sensitive recurrent ovarian carcinoma: a multicenter, randomized, double blind, placebo-controlled, phase III trial. Presented at: 2021 Society of Gynecologic Oncology Virtual Annual Meeting on Women's Cancer. Abstract 115572021.
    1. Tomao F, Bardhi E, Di Pinto A, Sassu CM, Biagioli E, Petrella MC, et al. . PARP inhibitors as maintenance treatment in platinum-sensitive recurrent ovarian cancer: an updated meta-analysis of randomized clinical trials according to BRCA mutational status. Cancer Treat Rev 2019;80:101909.
    1. Li N, Zhang Y, Wang J, Zhu J, Wang L, Wu X, et al. . Fuzuloparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer: a multicenter, randomized, double-blind, placebo-controlled, phase III trial. Presented at: 2021 Society of Gynecologic Oncology Virtual Annual Meeting on Women's Cancer Abstract115572021. Gynecol Oncol 2021;162:S57–8.
    1. Wilson MK, Pujade-Lauraine E, Aoki D, Mirza MR, Lorusso D, Oza AM, et al. . Fifth ovarian cancer consensus conference of the gynecologic cancer intergroup: recurrent disease. Ann Oncol 2017;28:727–32.
    1. Madariaga A, Lheureux S, Oza AM. Tailoring ovarian cancer treatment: implications of BRCA1/2 mutations. Cancers 2019;11:416.
    1. DiSilvestro P, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. . Efficacy of maintenance olaparib for patients with newly diagnosed advanced ovarian cancer with a BRCA mutation: subgroup analysis findings from the SOLO1 trial. J Clin Oncol 2020;38:3528–37.
    1. Kim H, Choi DH. Distribution of BRCA1 and BRCA2 mutations in Asian patients with breast cancer. J Breast Cancer 2013;16:357–65.
    1. Li N, Bu H, Liu J, Zhu J, Zhou Q, Wang L, et al. . An open-label, multicenter, single-arm, phase II study of fluzoparib in patients with germline BRCA1/2 mutation and platinum-sensitive recurrent ovarian cancer. Clin Cancer Res 2021;27:2452–8.
    1. Poveda A, Lheureux S, Colombo N, Cibula D, Lindemann K, Weberpals JI, et al. . Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): phase IIIb OPINION primary analysis. J Clin Oncol 2021;39:5545.
    1. Stone A, Gebski V, Davidson R, Bloomfield R, Bartlett JW, Sabin A. Exaggeration of PFS by blinded, independent, central review (BICR). Ann Oncol 2019;30:332–8.
    1. Rodriguez-Freixinos V, Fariñas-Madrid L, Gil-Martin M, Barretina-Ginesta P, Romeo M, Villacampa G, et al. . Chemotherapy and PARP inhibitors in heavily pretreated BRCA1/2 mutation ovarian cancer (BMOC) patients. Gynecol Oncol 2019;152:270–7.
    1. Agarwal A, Baghmar S, Dodagoudar C, Qureshi S, Khurana A, Vaibhav V, et al. . PARP inhibitor in platinum-resistant ovarian cancer: single-center real-world experience. JCO Glob Oncol 2021;7:506–11.
    1. Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018;29:iv259.
    1. LaFargue CJ, Dal Molin GZ, Sood AK, Coleman RL. Exploring and comparing adverse events between PARP inhibitors. Lancet Oncol 2019;20:e15–28.
    1. Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, et al. . Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomized, placebo-controlled, phase III trial. Lancet Oncol 2021;22:620–31.

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