Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer

Aikou Okamoto, Eiji Kondo, Toshiaki Nakamura, Satoshi Yanagida, Junzo Hamanishi, Kenichi Harano, Kosei Hasegawa, Takeshi Hirasawa, Kensuke Hori, Shinichi Komiyama, Motoki Matsuura, Hidekatsu Nakai, Hiroko Nakamura, Jun Sakata, Tsutomu Tabata, Kazuhiro Takehara, Munetaka Takekuma, Yoshihito Yokoyama, Yoichi Kase, Shuuji Sumino, Junpei Soeda, Ajit Suri, Daisuke Aoki, Toru Sugiyama, Aikou Okamoto, Eiji Kondo, Toshiaki Nakamura, Satoshi Yanagida, Junzo Hamanishi, Kenichi Harano, Kosei Hasegawa, Takeshi Hirasawa, Kensuke Hori, Shinichi Komiyama, Motoki Matsuura, Hidekatsu Nakai, Hiroko Nakamura, Jun Sakata, Tsutomu Tabata, Kazuhiro Takehara, Munetaka Takekuma, Yoshihito Yokoyama, Yoichi Kase, Shuuji Sumino, Junpei Soeda, Ajit Suri, Daisuke Aoki, Toru Sugiyama

Abstract

Objective: To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.

Methods: This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs.

Results: Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%.

Conclusion: Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.

Trial registration: ClinicalTrials.gov Identifier: NCT03759600.

Keywords: Japanese; Late-line Treatment; Niraparib; Ovarian Cancer; Phase 2; Salvage.

Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

Figures

Fig. 1. Waterfall plot of ORR in…
Fig. 1. Waterfall plot of ORR in FAS. Tumor BRCA1/2 mutation status is dichotomized as “Positive” or “Negative” (includes “Unknown”).
CR, complete response; FAS, full analysis set; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease; SoD, sum of diameters. *Best overall response was determined as SD/PR as tumor shrinkage corresponding to PR/CR was observed at only one time point but was not confirmed at a subsequent time point before data cut-off as required for confirmation of CR or PR.
Fig. 2. Kaplan-Meier plot of PFS in…
Fig. 2. Kaplan-Meier plot of PFS in FAS.
FAS, full analysis set; PFS, progression-free survival.

References

    1. Yi M, Dong B, Qin S, Chu Q, Wu K, Luo S. Advances and perspectives of PARP inhibitors. Exp Hematol Oncol. 2019;8:29.
    1. Sachdev E, Tabatabai R, Roy V, Rimel BJ, Mita MM. PARP inhibition in cancer: an update on clinical development. Target Oncol. 2019;14:657–679.
    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;375:2154–2164.
    1. González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381:2391–2402.
    1. Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20:636–648.
    1. U.S. Food and Drug Administration. Highlights of prescribing information: Niraparib (Zejula) prescribing information. Silver Spring, MD: U.S. FDA; 2020. [cited 2020 Oct 14]. Available from: .
    1. Sun K, Mikule K, Wang Z, Poon G, Vaidyanathan A, Smith G, et al. A comparative pharmacokinetic study of PARP inhibitors demonstrates favorable properties for niraparib efficacy in preclinical tumor models. Oncotarget. 2018;9:37080–37096.
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45:228–247.
    1. Berek JS, Matulonis UA, Peen U, Ghatage P, Mahner S, Redondo A, et al. Safety and dose modification for patients receiving niraparib. Ann Oncol. 2018;29:1784–1792.
    1. Matsumoto T, Takehara K, Takeshima N, Hamanishi J, Hasegawa K, Matsuura M, et al. Japan single arm study of niraparib (maintenance therapy) in patients with relapsed ovarian cancer: focus on initial safety results; The 72nd Annual Congress of the Japan Society of Obstetrics and Gynecology; 2020 April 23–28; p. Abstract P-32-1.

Source: PubMed

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