Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

被引：141

作者：

Hamanishi, Junzo ^{[1
]}

Takeshima, Nobuhiro ^{[2
,3
]}

Katsumata, Noriyuki ^{[4
]}

Ushijima, Kimio ^{[5
]}

Kimura, Tadashi ^{[6
]}

Takeuchi, Satoshi ^{[7
,8
]}

Matsumoto, Koji ^{[9
]}

Ito, Kimihiko ^{[10
]}

Mandai, Masaki ^{[1
,11
]}

Nakai, Hidekatsu ^{[11
]}

Sakuragi, Noriaki ^{[12
,13
]}

Watari, Hidemichi ^{[12
]}

Takahashi, Nobutaka ^{[14
]}

Kato, Hidenori ^{[15
]}

Hasegawa, Kosei ^{[16
]}

Yonemori, Kan ^{[17
]}

Mizuno, Mika ^{[18
,19
]}

Takehara, Kazuhiro ^{[20
]}

Niikura, Hitoshi ^{[21
,22
]}

Sawasaki, Takashi ^{[23
,24
]}

Nakao, Sari ^{[25
]}

Saito, Toshiaki ^{[26
]}

Enomoto, Takayuki ^{[27
]}

Nagase, Satoru ^{[28
]}

Suzuki, Nao ^{[29
]}

Matsumoto, Takashi ^{[30
]}

Kondo, Eiji ^{[31
]}

Sonoda, Kenzo ^{[32
,33
]}

Aihara, Satomi ^{[34
,35
]}

Aoki, Yoichi ^{[36
]}

Okamoto, Aikou ^{[37
]}

Takano, Hirokuni ^{[38
]}

Kobayashi, Hiroshi ^{[39
,40
]}

Kato, Hisamori ^{[41
]}

Terai, Yoshito ^{[42
,43
]}

Takazawa, Akira ^{[44
]}

Takahashi, Yusuke ^{[45
]}

Namba, Yoshinobu ^{[46
]}

Aoki, Daisuke ^{[47
]}

Fujiwara, Keiichi ^{[16
]}

Sugiyama, Toru ^{[7
,48
]}

Konishi, Ikuo ^{[49
]}

机构：

[1] Kyoto Univ, Dept Gynecol & Obstet, Grad Sch Med, Kyoto, Japan

[2] JFCR, Dept Gynecol, Canc Inst Hosp, Tokyo, Japan

[3] Int Univ Hlth & Welf Hosp, Dept Obstet & Gynecol, Otawara, Japan

[4] Musashikosugi Hosp, Dept Med Oncol, Nippon Med Sch, Kawasaki, Kanagawa, Japan

[5] Kurume Univ, Dept Obstet & Gynecol, Sch Med, Kurume, Fukuoka, Japan

[6] Osaka Univ, Dept Obstet & Gynecol, Grad Sch Med, Suita, Osaka, Japan

[7] Iwate Med Univ Hosp, Dept Obstet & Gynecol, Morioka, Iwate, Japan

[8] Kobe Tokushukai Hosp, Dept Gynecol, Kobe, Hyogo, Japan

[9] Hyogo Canc Ctr, Dept Med Oncol, Akashi, Hyogo, Japan

[10] Kansai Rosai Hosp, Dept Obstet & Gynecol, Amagasaki, Hyogo, Japan

[11] Kindai Univ, Dept Obstet & Gynecol, Fac Med, Osakasayama, Japan

[12] Hokkaido Univ, Dept Obstet & Gynecol, Grad Sch Med, Sapporo, Hokkaido, Japan

[13] Otaru Gen Hosp, Dept Gynecol, Otaru, Hokkaido, Japan

[14] Shizuoka Canc Ctr, Div Gynecol, Shizuoka, Japan

[15] Hokkaido Canc Ctr, Dept Gynecol, Sapporo, Hokkaido, Japan

[16] Saitama Med Univ, Dept Gynecol Oncol, Int Med Ctr, Hidaka, Japan

[17] Natl Canc Ctr, Dept Breast & Med Oncol, Tokyo, Japan

[18] Aichi Canc Ctr Hosp, Dept Obstet & Gynecol, Nagoya, Aichi, Japan

[19] Kagoshima Univ Hosp, Dept Obstet & Gynecol, Kagoshima, Japan

[20] Natl Hosp Org Shikoku Canc Ctr, Dept Gynecol Oncol, Matsuyama, Ehime, Japan

[21] Tohoku Univ, Dept Obstet & Gynecol, Grad Sch Med, Sendai, Miyagi, Japan

[22] Natl Hosp Org Sendai Med Ctr, Dept Obstet & Gynecol, Sendai, Miyagi, Japan

[23] Natl Hosp Org Kure Med Ctr, Dept Obstet & Gynecol, Kure, Japan

[24] SAWASAKI Obstet Gynecol Clin, Kure, Japan

[25] Univ Tsukuba Hosp, Fac Med, Dept Obstet & Gynecol, Tsukuba, Ibaraki, Japan

[26] Natl Hosp Org Kyushu Canc Ctr, Gynecol Serv, Fukuoka, Fukuoka, Japan

[27] Niigata Univ, Dept Obstet & Gynecol, Grad Sch Med & Dent Sci, Niigata, Japan

[28] Yamagata Univ Hosp, Dept Obstet & Gynecol, Yamagata, Japan

[29] St Marianna Univ, Dept Obstet & Gynecol, Sch Med, Kawasaki, Kanagawa, Japan

[30] Ehime Univ Hosp, Dept Obstet & Gynecol, Toon, Japan

[31] Mie Univ Hosp, Dept Obstet & Gynecol, Tsu, Mie, Japan

[32] Kyushu Univ Hosp, Dept Obstet & Gynecol, Fukuoka, Fukuoka, Japan

[33] Natl Hosp Org Kyushu Canc Ctr, Dept Gynecol Oncol, Fukuoka, Fukuoka, Japan

[34] Saga Univ Hosp, Fac Med, Dept Obstet & Gynecol, Saga, Japan

[35] Eguchi Hosp, Dept Med Oncol, Saga, Japan

[36] Univ Ryukyus Hosp, Dept Obstet & Gynecol, Nishihara, Okinawa, Japan

[37] Jikei Univ Hosp, Dept Obstet & Gynecol, Tokyo, Japan

[38] Jikei Univ, Dept Obstet & Gynecol, Kashiwa Hosp, Kashiwa, Chiba, Japan

[39] Nara Med Univ Hosp, Dept Obstet & Gynecol, Kashihara, Nara, Japan

[40] Ms Clin MayOne, Kashihara, Nara, Japan

[41] Kanagawa Canc Ctr, Dept Gynecol, Yokohama, Kanagawa, Japan

[42] Osaka Med Coll Hosp, Dept Gynecol Oncol, Takatsuki, Osaka, Japan

[43] Kobe Univ, Obstet & Gynecol, Grad Sch Med, Kobe, Hyogo, Japan

[44] Ono Pharmaceut Co Ltd, Data Sci, Osaka, Japan

[45] Ono Pharmaceut Co Ltd, Oncol Clin Dev Unit, Osaka, Japan

[46] Ono Pharmaceut Co Ltd, Clin Sci, Osaka, Japan

[47] Keio Univ, Dept Obstet & Gynecol, Sch Med, Tokyo, Japan

[48] St Marys Hosp, Dept Obstet & Gynecol, Kurume, Fukuoka, Japan

[49] Natl Hosp Org Kyoto Med Ctr, Kyoto, Japan

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2021年 / 39卷 / 33期

关键词：

PHASE-III TRIAL; ANTI-PD-1; ANTIBODY; ANTITUMOR-ACTIVITY; CHEMOTHERAPY; SAFETY; AVELUMAB; CELLS;

D O I：

10.1200/JCO.21.00334

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received <= 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of <= 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m(2) for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m(2) once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer. (C) 2021 by American Society of Clinical Oncology

引用

页码：3671 / +

页数：16

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